subject:(biophysics)

University of Georgia

1. Zhou, Dayong. Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G.

Degree: PhD, Biochemistry and Molecular Biology, 2011, University of Georgia

URL: http://purl.galileo.usg.edu/uga_etd/zhou_dayong_201112_phd

► The human immunodeficiency virus type-1 (HIV-1) Virus Infectivity Factor (Vif) mediates the degradation of a cellular antiviral factor, Apolipoprotein B mRNA-editing enzymecatalytic, polypeptide-like 3G (APOBEC3G),… (more)

▼ The human immunodeficiency virus type-1 (HIV-1) Virus Infectivity Factor (Vif) mediates the degradation of a cellular antiviral factor, Apolipoprotein B mRNA-editing enzymecatalytic, polypeptide-like 3G (APOBEC3G), by serving as an adaptor that bridges the APOBEC3G and the E3 ubiquitin ligase complex. Human APOBEC3G is a potent inhibitor of retroviruses and functions to deaminate cytidines to uridines in HIV-1 ssDNA during viral replication. Thus, degradation of APOBEC3G neutralized one of the body’s main defenses against HIV. The characterization of the Vif - APOBEC3G interaction is important to understand how Vif functions in suppressing APOBEC3G activity, which could lead to new and better HIV drugs and therapies. However, the study of the Vif - APOBEC3G complex has been severely hindered by the fact that both Vif and APOBEC3G proteins have proved to be very difficult to express and purify in large amounts. The goal of the work presented in this dissertation is twofold: (1) to address the current bottleneck for Vif and APOBEC3G protein production by developing expression and purification protocols that are capable of producing milligram quantities of both proteins and (2) characterize the Vif protein and the Vif-APOBEC3G complex using biochemical and biophysical methods. Milligram quantities of Vif were produced using the bacterial expression system. The protein has been characterized using a number of biochemical/biophysical techniques and suggest that Vif is an unstructured protein under native conditions. Circular dichroism (CD) indicated a random coil structure with few secondary structural elements. Nuclear magnetic resonance (NMR) produced a spectrum characteristic of an unstructured protein. Small-angle Xray scattering (SAXS) studies suggested that Vif forms multimers with a compact core in solution. Overall, these results support the idea that Vif is an intrinsically unstructured protein in solution. The full-length APOBEC3G was produced using a baculovirus expression system. Both monomeric and dimeric APOBEC3G forms were observed providing the first direct evidence for APOBEC3G dimerization. The binding kinetics of Vif-APOBEC3G interaction was determined by surface plasmon resonance (Biacore). Interestingly, full-length Vif was observed to interact with APOBEC3G dimers (KD=0.2 nM) with an affinity that is 1000-fold greater than that observed for the APOBEC3G monomers (KD=200 nM). Advisors/Committee Members: John Rose.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Zhou, D. (2011). Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G. (Doctoral Dissertation). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/zhou_dayong_201112_phd

Chicago Manual of Style (16^th Edition):

Zhou, Dayong. “Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G.” 2011. Doctoral Dissertation, University of Georgia. Accessed January 29, 2020. http://purl.galileo.usg.edu/uga_etd/zhou_dayong_201112_phd.

MLA Handbook (7^th Edition):

Zhou, Dayong. “Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G.” 2011. Web. 29 Jan 2020.

Vancouver:

Zhou D. Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G. [Internet] [Doctoral dissertation]. University of Georgia; 2011. [cited 2020 Jan 29]. Available from: http://purl.galileo.usg.edu/uga_etd/zhou_dayong_201112_phd.

Council of Science Editors:

Zhou D. Biochemical and biophysical investigations of HIV-1 viral infectivity factor and its interaction with human APOBEC3G. [Doctoral Dissertation]. University of Georgia; 2011. Available from: http://purl.galileo.usg.edu/uga_etd/zhou_dayong_201112_phd

University of California, San Francisco

2. Greenberg, Charles Harold. Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data.

Degree: 2016, University of California, San Francisco

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10165386

► Advances in electron microscopy (EM) allow for structure determination of large macromolecular machines at increasingly high resolutions. A key step in this process is… (more)

▼ Advances in electron microscopy (EM) allow for structure determination of large macromolecular machines at increasingly high resolutions. A key step in this process is interpreting the EM density map with structural models of maximal accuracy and optimal precision. Model precision should be determined by the uncertainty in the experimental data; however, current methods only set uncertainty in an <i>ad hoc</i> manner with arbitrary weight terms. Thus, there is a need for more objective methods. In Chapter 2, I present a novel Bayesian approach to modeling macromolecular structures based on EM density maps. The key advancement is the development of a scoring function that uses the local uncertainty of the density map to set the data weight and allows for correlation between neighboring density values. Unlike traditional approaches, the score does not require an expert user to set arbitrary parameters. I assessed the accuracy of models generated by this approach with a set of experimentally-derived, previously-published EM data of macromolecular complexes at varying resolutions from 3 to 6Å. I found that this approach leads to higher fluctuations in the model ensemble in locations with higher local uncertainty, and obtained accurate ensembles for a 3.2Å resolution map of Trpvl and 3.4Å and 5.4Å resolution maps of γ-secretase. In Chapter 3, I present models of the γ-tubulin small complex in two functional states based on a challenging data set consisting of low-resolution EM density maps and a remotely related structure. Here, I used a traditional scoring techniques, but extensively sampled alignments and conformations in order to ensure that the model ensemble reflected the uncertainty in the data. The resulting models form a tight cluster for each state and were consistent with a set of newly reported chemical cross-links. Comparing the two states, I found significant structural differences and predict stabilizing interactions of the two states. The work in this chapter shows the difficulties of traditional modeling and serves as motivation for the methods developed in Chapter 2. Both approaches are incorporated into the open source <i>Integrative Modeling Platform</i> (IMP) package, enabling integration with multiple other data types and usage of myriad sampling and analysis tools.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Greenberg, C. H. (2016). Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data. (Thesis). University of California, San Francisco. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10165386

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Greenberg, Charles Harold. “Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data.” 2016. Thesis, University of California, San Francisco. Accessed January 29, 2020. http://pqdtopen.proquest.com/#viewpdf?dispub=10165386.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Greenberg, Charles Harold. “Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data.” 2016. Web. 29 Jan 2020.

Vancouver:

Greenberg CH. Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data. [Internet] [Thesis]. University of California, San Francisco; 2016. [cited 2020 Jan 29]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10165386.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Greenberg CH. Inferring Optimally Precise and Maximally Accurate Models from Electron Microscopy Data. [Thesis]. University of California, San Francisco; 2016. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10165386

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Temple University

3. Ayesa, Umme. CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE.

Degree: PhD, 2016, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,368614

►

Biochemistry

One of earlier challenges in treating cancer was utilizing drugs that are powerful yet do not cause severe toxicity to patients. Although the use… (more)

▼

Biochemistry

One of earlier challenges in treating cancer was utilizing drugs that are powerful yet do not cause severe toxicity to patients. Although the use of liposomal drugs has somewhat met that challenge, our objective now is to create liposomal drugs with an even better drug efficacy and further reduced toxicity. Doxorubicin hydrochloride (DXO), for example, is an anticancer drug used to treat many types of cancers, but it is toxic to the gastrointestinal tract and the heart. Encapsulating DXO into liposomes as done in the first FDA-approved liposomal DXO, Doxil, minimizes toxicity and improves the half-life, allowing more opportunities for the drug to reach the tumor. While liposomal DXO is in the market with an annual sale of approximately 450 million dollars, the addition of cholesterol and lipids with polyethylene glycol (PEG) in the formulation increase liposome stability and circulation time, but can give rise to other concerns such as potential harm to the patient and reduction in drug loading/release. In addition, in hopes of increasing drug accumulation at the diseased tissue, the use of active or targeted nanoparticles has been explored for selective drug delivery. However, despite ongoing efforts to design and test targeted nanocarriers for drug delivery, there is no known targeted liposome commercially available at this time. This illustrates that there is still room to improve the formulation of the liposomal carriers in the areas of stability, specificity to the cancer sites, and maximum drug at diseased sites. The main focus of our research is to develop novel liposomal carriers that have a higher therapeutic index and lower cytotoxicity than currently used liposomal drugs. In this research, we were able to construct two stable liposomal systems. First, we constructed a liposomal system having the ability to specifically target phosphatidylserine (PS) exposed tissues. This liposomal system contains 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and hydrophobic PS-targeting molecule bis-dipicolylamine-Zn-Cy3[C22,22] (abbreviated DPA-Cy3[22,22]). We have tested stability and PS binding ability of DPA-Cy3[22,22]/POPC liposomal carriers using light scattering and ion-exchange chromatography, respectively. In addition, with confocal microscopy and flow cytometry, we have tested DPA-Cy3[22,22]/POPC liposomes’ affinity to cancer cells. Furthermore, cell viability assay was used to determine the cytotoxic effect of DPA-Cy3[22,22]/POPC liposomes on cancer cells and non-cancer cells. In short, we found that DPA-Cy3[22,22]/POPC liposomes were stable, displayed binding to PS-exposed cells, and were taken up by PS-exposed cells inducing considerable cytoxicity. Second, we have developed and characterized the physical properties of thermosensitive liposomes made of archaeal bipolar tetraether lipids (BTL) and “conventional” monopolar diester lipids. These liposomes are also termed hybrid archaeosomes. Specifically, we used the polar lipid fraction E (PLFE) isolated from the thermoacidophilic…

Advisors/Committee Members: Chong, Parkson Lee-Gau;, Rothberg, Brad S., Gamero, Ana, Grubmeyer, Charles, Ramirez, Servio;.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ayesa, U. (2016). CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,368614

Chicago Manual of Style (16^th Edition):

Ayesa, Umme. “CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE.” 2016. Doctoral Dissertation, Temple University. Accessed January 29, 2020. http://digital.library.temple.edu/u?/p245801coll10,368614.

MLA Handbook (7^th Edition):

Ayesa, Umme. “CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE.” 2016. Web. 29 Jan 2020.

Vancouver:

Ayesa U. CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE. [Internet] [Doctoral dissertation]. Temple University; 2016. [cited 2020 Jan 29]. Available from: http://digital.library.temple.edu/u?/p245801coll10,368614.

Council of Science Editors:

Ayesa U. CHARACTERIZATION OF THERMOSENSITIVE HYBRID ARCHAEOSOMES AND DPA-CY3[22,22]/POPC LIPOSOMES AND IN VITRO EVALUATION OF THEIR POTENTIAL USEFULNESS IN TARGETED DELIVERY AND CONTROLLED RELEASE. [Doctoral Dissertation]. Temple University; 2016. Available from: http://digital.library.temple.edu/u?/p245801coll10,368614

University of California – San Diego

4. Tiee, Nicholas Shaofeng. On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases.

Degree: Chemistry, 2018, University of California – San Diego

URL: http://www.escholarship.org/uc/item/6h4666vq

► Interleukin-36 receptor antagonist is a cytokine that recently has been implicated in psoriatic diseases. Genome wide association studies observed single point mutations in the IL36RN… (more)

▼ Interleukin-36 receptor antagonist is a cytokine that recently has been implicated in psoriatic diseases. Genome wide association studies observed single point mutations in the IL36RN gene which were associated with psoriasis patients. Characterizing how IL-36Ra works at a molecular level is critical in determining how diseases states may arise. Two observations regarding IL-36Ra were studied in detail in this work. Firstly, IL-36Ra was observed to be highly sensitive to N-terminal cleavage, in that the removal of the initiator methionine can activate the cytokine to its full activity. Secondly, IL-36Ra contains a unique disulfide bond that is not found in any related family member. Chapter 3 details the NMR (Nuclear Magnetic Resonance) assignments of IL-36Ra necessary to solve the solution structure and probe phenomena at a residue resolution. Chapter 4 details our observations of the structural changes and dynamics changes in IL-36Ra when comparing full length IL-36Ra to the N-terminal methionine cleaved IL-36Ra. Using a combination of NMR and hydrogen/deuterium we observed subtle differences in the two isoforms. The structural studies implicated the barrel structure in allowing allosteric transmission from N-terminal face to the opposite side of the molecule. Additionally, our dynamics studies revealed changes in the motions of the loops in the cap of the protein that are responsible for receptor binding. The changes were likely mediated via the residues at the cap-barrel interface which allowed changes in the barrel architecture to affect the loops in the cap subdomain.Chapter 5 details our observations of the structural changes as well as dynamics changes in IL-36Ra when comparing oxidized IL-36Ra to the reduced IL-36Ra. Our data shows that the reduced form is highly destabilized overall, and specifically in the strands local to the disulfide bond. However, H/D exchange revealed that the residue diametrically opposed to the disulfide increased in protection from exchange, whereas most other residues decreased after the removal of the disulfide bond. These observations allowed us to construct a model in which the barrel expands without the presence of a disulfideLastly, Chapter 6 details the changes in H/D protection when IL-36Ra interacts with its receptor IL-36R. Different exchange profiles were observed for the two N-terminal isoforms when interacting with IL-36R. Using the observations, we were able to build a model in which the fully active IL-36Ra likely tunes the receptor off rate through the N-terminal/2nd trefoil interface that does not exist in the less active isoform.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tiee, N. S. (2018). On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/6h4666vq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tiee, Nicholas Shaofeng. “On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases.” 2018. Thesis, University of California – San Diego. Accessed January 29, 2020. http://www.escholarship.org/uc/item/6h4666vq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tiee, Nicholas Shaofeng. “On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases.” 2018. Web. 29 Jan 2020.

Vancouver:

Tiee NS. On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/6h4666vq.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tiee NS. On the Structure and Dynamics of IL-36Ra, a Key Player in Psoriatic and Inflammatory Diseases. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/6h4666vq

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Maulbetsch, William. Nanopore Mass Spectrometry.

Degree: Department of Physics, 2018, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:792908/

► My research is motivated by an idea for a new method of sequencing individual biopolymers, including proteins and nucleic acids, that combines mass spectrometry with… (more)

▼ My research is motivated by an idea for a new method of sequencing individual biopolymers, including proteins and nucleic acids, that combines mass spectrometry with nanopores. The basic idea is to take advantage of a mass spectrometer’s ability to identify monomers by their mass, paired with a nanopore’s ability to force biopolymers into a linear configuration so that their monomers are delivered into the mass spectrometer in sequence. I address two major challenges for such a method to succeed. First, monomers must be ionized and transferred to the gas phase, necessary for mass analysis. Second, before monomers are transferred into vacuum, but after they are cleaved in solution from their parent polymer, they undergo random thermal motion which tends to randomize their sequential order. This order between neighboring monomers must be preserved between when they are cleaved and when they exit into this charged gas phase. If a strong electric field is applied to the liquid surface at the tip of a solution filled needle-like capillary, it will emit a spray of ions through a process known as electrospray. Ions emitted in this spray can leave the liquid surface in two main ways. They can leave inside large multiply charged liquid drops usually on the order of 100's nm in diameter, or they can leave the surface individually as partially solvated ions, called ion clusters. Since monomer ions trapped in drops would prevent us from obtaining sequence information, I conducted experiments on a version of electrospray known as ion evaporation in which ion clusters in solution are emitted directly from the electrospray capillary’s liquid surface. I have helped to build and test a machine capable of investigating this mechanism of ion production from electrospray using capillaries with nanoscale tip openings. I present measurements of the voltages necessary to produce electrospray for capillaries in this nanoscale regime. Generally, the electrospray is composed of both ion clusters and charged droplets, and the latter must be suppressed for the success of this sequencing strategy. I compare the number of ion clusters that reach our mass spectrometer with the total number of ions leaving our nanocapillaries to explore the conditions under which ion cluster production is favored over drop formation. Finally, I present a simplified one dimensional model of the dynamics of Brownian particles in the electric fields at the tips of these electrospraying capillaries to estimate the conditions under which sequential information is preserved. Advisors/Committee Members: Stein, Derek (Advisor), Ying, See-Chen (Reader), Mandre, Shreyas (Reader).

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maulbetsch, W. (2018). Nanopore Mass Spectrometry. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792908/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Maulbetsch, William. “Nanopore Mass Spectrometry.” 2018. Thesis, Brown University. Accessed January 29, 2020. https://repository.library.brown.edu/studio/item/bdr:792908/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Maulbetsch, William. “Nanopore Mass Spectrometry.” 2018. Web. 29 Jan 2020.

Vancouver:

Maulbetsch W. Nanopore Mass Spectrometry. [Internet] [Thesis]. Brown University; 2018. [cited 2020 Jan 29]. Available from: https://repository.library.brown.edu/studio/item/bdr:792908/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Maulbetsch W. Nanopore Mass Spectrometry. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792908/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

6. Fan, Yi. Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids.

Degree: School of Engineering, 2018, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:792895/

► Active matter systems remain in a far-from-equilibrium state due to the motion generated at small scales by their self-driven constituents. These systems can exhibit complex… (more)

▼ Active matter systems remain in a far-from-equilibrium state due to the motion generated at small scales by their self-driven constituents. These systems can exhibit complex behavior, such as collective motion and pattern formation, and understanding the governing principles of active matter systems is tremendously challenging. The active fluids studied here are artificial systems assembled from kinesin-driven bundled microtubule networks. We focus on characterizing the three-dimensional dynamical behavior and structure of the active fluids, subject to different confining geometries. The systems are measured using an epi-fluorescence microscope equipped with two-color fluorescent imaging and synchronized z-scanning. The fluorescently-labeled microtubules (red) and the dispersed passive fluorescent tracer particles (blue) are simultaneously observed at multiple z-positions. A three-dimensional tracking method, using the Airy disks of diffracted particles, extends the measurement to the entire observation volume. The active systems exhibit transitions between two dynamical states — a chaotic turbulent state and a coherent state — depending on the confining geometry. The turbulent flows have no net transport while, in contrast, the coherent flows exhibit long-term self-pumping motion. We find that the self-pumping motion correlates with a three-dimensional flow structure, which is affected by the dimension and the surface treatment of the confinement. Besides, the coherent flows can be scaled across different dimensions and surface conditions. The influence of boundaries is further studied in the chaotic turbulent state of bulk active systems. Far from confining boundaries, the active systems exhibit small-scale isotropy, however, we obtain evidence of large-scale collective motion that extends beyond the scale of our measurement. As the confinement increases, the active systems preserve the small-scale isotropy, but demonstrate increasing large-scale anisotropy, a decrease in the temporal correlation (flow "memory") and a reduction in the characteristic size of the structure. Lastly, our results show that the large-scale dynamics in the active systems, either in the turbulent state or in the coherent state, hardly affect the micrometer-scale interaction between an active microtubule bundle and the motion of its nearby passive tracer particles. Advisors/Committee Members: Breuer, Kenneth S. (Advisor), Powers, Thomas R. (Reader), Tang, Jay X. (Reader).

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fan, Y. (2018). Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792895/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fan, Yi. “Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids.” 2018. Thesis, Brown University. Accessed January 29, 2020. https://repository.library.brown.edu/studio/item/bdr:792895/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fan, Yi. “Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids.” 2018. Web. 29 Jan 2020.

Vancouver:

Fan Y. Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids. [Internet] [Thesis]. Brown University; 2018. [cited 2020 Jan 29]. Available from: https://repository.library.brown.edu/studio/item/bdr:792895/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fan Y. Three-dimensional measurements of dynamics and structure in kinesin-driven active fluids. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792895/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

7. Qu, Zijie. Flagellated bacteria swimming in polymer solutions.

Degree: Fluids and Thermal Sciences, 2018, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:792806/

► The research is motivated by some previously-reported conflicting observations and explanations regarding the motility of flagellated bacteria swimming in polymer solutions. Three-dimensional real-time tracking microscopy… (more)

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Qu, Z. (2018). Flagellated bacteria swimming in polymer solutions. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792806/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Qu, Zijie. “Flagellated bacteria swimming in polymer solutions.” 2018. Thesis, Brown University. Accessed January 29, 2020. https://repository.library.brown.edu/studio/item/bdr:792806/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Qu, Zijie. “Flagellated bacteria swimming in polymer solutions.” 2018. Web. 29 Jan 2020.

Vancouver:

Qu Z. Flagellated bacteria swimming in polymer solutions. [Internet] [Thesis]. Brown University; 2018. [cited 2020 Jan 29]. Available from: https://repository.library.brown.edu/studio/item/bdr:792806/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Qu Z. Flagellated bacteria swimming in polymer solutions. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792806/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rice University

8. Stagg, Loren. Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin.

Degree: PhD, Engineering, 2010, Rice University

URL: http://hdl.handle.net/1911/61970

► The intracellular environment in which most proteins fold and function contains a range of biomolecules that results in significant volume exclusion, thus contrasting to the… (more)

▼ The intracellular environment in which most proteins fold and function contains a range of biomolecules that results in significant volume exclusion, thus contrasting to the dilute buffer conditions common to most in vitro studies. In addition to intracellular macromolecular crowding, cells are ionic in nature, and although the Hofmeister series of ions has its origin in a work from 1888, much is still unclear concerning how small, charged ions affect protein properties. This thesis summarizes in vitro work assessing the effects of macromolecular crowding and small ions on the biophysical properties of a model protein – Desulfovibrio desulfuricans flavodoxin. Flavodoxin is a small (15.7 kDa), single domain, cytoplasmic protein with alpha-helical and parallel beta-sheet secondary structural elements arranged in one of the five most common protein folds (the flavodoxin-like fold). Using a range of biophysical/spectroscopic methods (e.g., circular dichroism (CD), fluorescence, calorimetry, stopped-flow mixing) along with synthetic crowding agents (e.g., Ficoll and dextran), I have found that macromolecular crowding increases the secondary structural content of folded flavodoxin (toward that found in the crystal structure), increases flavodoxin thermal stability, and affects both the accumulation of a misfolded intermediate and the rate of proper protein folding. Collaborative in silico simulations employing Go-like modeling of apoflavodoxin in the presence of large, inert crowding agents agrees with my in vitro work and provides structural and mechanistic information with residue-specific resolution. We also found that small cations and anions in physiologically relevant concentrations (≤ 250 mM) increase flavodoxin thermal stability significantly. Both cations and anions in higher concentrations (300 mM-.75 M) affect oppositely charged proteins similarly suggesting that surface electrostatic charge plays only a minor role in mediating ionic effects on protein thermal stability. At all ion concentrations, ionic effects on protein stability are correlated to ion hydration (and thus the Hofmeister series). Our work suggests a dominant role for the peptide bond in coordinating ions at higher concentrations. This thesis work suggests that the crowded and ionic nature of the intracellular milieu can elicit changes to the structure, dynamics, stability, and folding mechanism of proteins which may not be captured in vitro using dilute buffer conditions. Advisors/Committee Members: Wittung-Stafshede, Pernilla (advisor).

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Stagg, L. (2010). Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/61970

Chicago Manual of Style (16^th Edition):

Stagg, Loren. “Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin.” 2010. Doctoral Dissertation, Rice University. Accessed January 29, 2020. http://hdl.handle.net/1911/61970.

MLA Handbook (7^th Edition):

Stagg, Loren. “Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin.” 2010. Web. 29 Jan 2020.

Vancouver:

Stagg L. Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin. [Internet] [Doctoral dissertation]. Rice University; 2010. [cited 2020 Jan 29]. Available from: http://hdl.handle.net/1911/61970.

Council of Science Editors:

Stagg L. Effects of macromolecular crowding and small ions on the folding, structure, and stability of Desulfovibrio desufuricans flavodoxin. [Doctoral Dissertation]. Rice University; 2010. Available from: http://hdl.handle.net/1911/61970

Rice University

9. Shen, Jun. Study of influenza virus hemagglutinin.

Degree: PhD, Engineering, 2010, Rice University

URL: http://hdl.handle.net/1911/61974

► The suddenly global outbreak of 2009 H1N1 Flu reminds human being the danger and severity of influenza virus. The gene of the new strain come… (more)

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Shen, J. (2010). Study of influenza virus hemagglutinin. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/61974

Chicago Manual of Style (16^th Edition):

Shen, Jun. “Study of influenza virus hemagglutinin.” 2010. Doctoral Dissertation, Rice University. Accessed January 29, 2020. http://hdl.handle.net/1911/61974.

MLA Handbook (7^th Edition):

Shen, Jun. “Study of influenza virus hemagglutinin.” 2010. Web. 29 Jan 2020.

Vancouver:

Shen J. Study of influenza virus hemagglutinin. [Internet] [Doctoral dissertation]. Rice University; 2010. [cited 2020 Jan 29]. Available from: http://hdl.handle.net/1911/61974.

Council of Science Editors:

Shen J. Study of influenza virus hemagglutinin. [Doctoral Dissertation]. Rice University; 2010. Available from: http://hdl.handle.net/1911/61974

Purdue University

10. Lin, David Yin-wei. Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7.

Degree: 2016, Purdue University

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10160100

► Many microbial pathogens deliver effector proteins, via type III secretion system, into infected host cells. Elucidating the function of these effectors is essential for… (more)

▼ Many microbial pathogens deliver effector proteins, via type III secretion system, into infected host cells. Elucidating the function of these effectors is essential for our understanding of pathogenesis. Here I describe biochemical and structural characterization of an effector protein (NleL) from E. coli O157:H7, a widespread pathogen causing severe food borne diseases. NleL functionally and structurally mimics eukaryotic HECT E3 ligases and catalyzes formation of unanchored polyubiquitin chains using K6 and K48 linkage. The catalytic cysteine residue forms a thioester intermediate with ubiquitin. The structure of NleL contains two domains, a β-helix domain formed by pentapeptide repeats and a bilobed catalytic domain reminiscent of the N- and C-lobe architecture of HECT E3sstructures of NleL observed in two crystal forms revealed a large range of different positions of the C-lobe relative to the N-lobe, indicating that the helix linking the two lobes is extremely flexible. Comparing the structure of NleL with that of the Salmonella homolog SopA showed that the orientation of the C-lobes differ by as much as 108?, suggesting that large movements of the C-lobe may be required to facilitate the transfer of ubiquitin from E2 to the substrate. In the structure of NleL/UbcH7 complex, UbcH7 binds at the end of the N-lobe that is closer to the C-lobe as observed in the structure of SopA/UbcH7 complex. The conserved phenylalanine of E2s (Phe63 of UbcH7) is involved heavily in the binding. The C-lobe of NleL in the complex rotates as much as ~168? towards UbcH7 compared with the structures of the isolated NleLs and the catalytic cysteines of E2 and E3 are within 7? of each other. In the structure of SopA/UbcH7 complex, the C-lobe bends towards the putative substrate binding domain (β-helix domain). The orientation of the C-lobes in the NleL and SopA complexes differs by ~180?, demonstrating that large movements of the C-lobes are possible, and the two complexes could represent two different stages of the transfer of ubiquitin from E2 to the substrate. These results provide critical knowledge towards understanding the molecular mechanism by which pathogens utilize the host ubiquitination system during infection.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Lin, D. Y. (2016). Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7. (Thesis). Purdue University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10160100

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lin, David Yin-wei. “Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7.” 2016. Thesis, Purdue University. Accessed January 29, 2020. http://pqdtopen.proquest.com/#viewpdf?dispub=10160100.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lin, David Yin-wei. “Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7.” 2016. Web. 29 Jan 2020.

Vancouver:

Lin DY. Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7. [Internet] [Thesis]. Purdue University; 2016. [cited 2020 Jan 29]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10160100.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lin DY. Biochemical and Structural Studies of a HECT-Like Ubiquitin Ligase from E. Coli O157|H7. [Thesis]. Purdue University; 2016. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10160100

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

11. Yang, Yi. Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface.

Degree: PhD, Physics, 2009, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1261450640

► Protein hydration dynamics are of fundamental importance to a protein’s structure and function as well as its recognition and interaction with substrates. Here, we present… (more)

▼ Protein hydration dynamics are of fundamental importance to a protein’s structure and function as well as its recognition and interaction with substrates. Here, we present our studies of the ultrafast hydration dynamics on the protein surface of apomyoglobin (apoMb) and at protein-DNA interfaces of Polymerase ß (Pol ß) and DNA polymerase IV (Dpo4). The natural fluorescent amino acid tryptophan was applied as a local optical probe to detect environmental response using the femtosecond-resolved fluorescence up-conversion technique and reveal the hydration dynamics around proteins. With site-directed mutagenesis, tryptophan was placed at desired positions to investigate hydration dynamics on protein surfaces and interfaces in protein-DNA complexes with single-residue resolution. Sixteen single-tryptophan-containing mutants of apoMb were studied to map the global hydration dynamics around the protein surface in both the native and molten globule states. Two distinct hydration components are observed on time scales of a few (1-8 ps) and tens to hundreds of picoseconds (20-200 ps), reflecting the initial collective water relaxation and subsequent hydrogen-bond networking restructuring, respectively, and both time scales are strongly correlated with protein’s local structures and chemical properties. For Pol ß, tryptophan was introduced one at a time at different positions around the surface of DNA binding pocket to map the water motions at the interface of the complex. Totally, twelve mutants were examined and a bimodal distribution of time scales for the water-network relaxation was also observed. The two components (0.9~4.9 ps and 31~100 ps) of the hydration dynamics reveal relatively fast water motions around the DNA binding pocket, which facilitate the recognition and interaction between the protein and the substrate. The hydration dynamics of protein-DNA complex show that the water motions (2.2~7 ps and 77~156 ps) at the interface, which is still solvent accessible in the presence of DNA as indicated by the steady-state tryptophan emission peaks (337~342 nm), slows down reflecting the rigid water network and tight local structure of the complex, but are still fast enough in the active site and at the entrance of dNTP for the enzyme to incorporate the incoming nucleotide. Similarly, four single-tryptophan-containing mutants of Dpo4 were examined to reveal the water motions around the DNA binding pocket and at the Dpo4 active site. The hydration dynamics indicate that water relaxation is still fast both at the interface (2.3~2.8 ps and 77~84 ps) and in the active site (3 ps and 107 ps), reflecting a flexible structure of water networks in these recognition and binding regions. Further, the hydration dynamics of the active site in the protein-DNA complex show slower water motions (4.8 ps and 164 ps) indicating the rigid water network and local structures after binding of the DNA substrate. Moreover, the anisotropy dynamics reveal that the active site structure of Pol ß is rigid, while the active site of Dpo4 is spacious… Advisors/Committee Members: Zhong, Dongping (Committee Chair).

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Yang, Y. (2009). Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1261450640

Chicago Manual of Style (16^th Edition):

Yang, Yi. “Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface.” 2009. Doctoral Dissertation, The Ohio State University. Accessed January 29, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261450640.

MLA Handbook (7^th Edition):

Yang, Yi. “Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface.” 2009. Web. 29 Jan 2020.

Vancouver:

Yang Y. Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface. [Internet] [Doctoral dissertation]. The Ohio State University; 2009. [cited 2020 Jan 29]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1261450640.

Council of Science Editors:

Yang Y. Ultrafast Hydration Dynamics on Protein Surface and at Protein-DNA Interface. [Doctoral Dissertation]. The Ohio State University; 2009. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1261450640

The Ohio State University

12. Perrine, Zoee Gokhale. Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii.

Degree: PhD, Biophysics, 2010, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291063978

► Photosystem II (PSII) is a water-plastoquinone oxidoreductase and is central to the process of oxygenic photosynthesis. It is associated with a peripheral light-harvesting antenna… (more)

▼ Photosystem II (PSII) is a water-plastoquinone oxidoreductase and is central to the process of oxygenic photosynthesis. It is associated with a peripheral light-harvesting antenna that primarily functions in light absorption and transfer of excitation energy to the PSII reaction center (RC), where charge separation occurs. Photosynthetic productivity is in part determined by the light utilization capacity of algal cells. Wild-type algae light saturate photosynthesis at only 25% of full sunlight intensity which leads to low productivities under high light. It was our objective to increase light utilization efficiency and productivities of algal cultures by reducing/optimizing Chl b synthesis and the size of the PSII peripheral antenna. RNAi-mediated silencing of the Chl b synthesis gene, CAO, resulted in transgenics that had reduced PSII peripheral antenna sizes, up to ~2 fold higher light-saturated photosynthesis rates and 35% greater growth at high light intensities, while photoautotrophic growth at low light intensities was unimpaired. In addition, the dynamic modulation of PSII antenna size was obtained through the post-transcriptional regulation of Chl b synthesis using the light-responsive translational inhibitor protein, NAB1. Photosynthetic productivity is also dependent on the redox properties and energetic gaps between electron donors and acceptors in PSII which in turn can be influenced by the protein microenvironment. We modified the local protein environment of ChlD1, the likely primary donor in PS II, to elucidate its function in charge separation and to study the effects of the protein environment on its redox properties. Analysis of the resulting transgenics indicated that the mutagenesis of D1-T179 to D, N or H induces a shift in the Em of P680/P680+ to more positive values, causing an acceleration of charge recombination due to a decrease in the energetic gap between the primary radical pair and the S2QA-(QB-) state. Our results show that the nature of the D1-179 residue is important in mediating excitation energy transfer to the RC and in determining the redox properties of the primary electron donor in PSII. The primary electron acceptor in PSII is PheoD1 and its redox properties are modulated by the D1-E130 amino acid residue in Chlamydomonas which serves as a hydrogen-bond donor to the PheoD1 head group. D2-Q129 is the inactive branch residue analogous to D1-E130 and is found to be too distant from the PheoD2 head group to serve as a viable hydrogen-bond donor. Our objective was to characterize the function of this highly conserved inactive branch residue by replacing it with a non-conservative leucine or a conservative histidine residue. The mutagenesis of D2-Q129 was shown to decrease the redox gap between QA and QB due to a lowering of the redox potential of QB. Further, an increased yield of S2QB- charge recombination was seen in the D2-Q129 mutants, which led to an increased susceptibility to photoinhibitory light presumably due to 3P680-mediated oxidative damage. This study… Advisors/Committee Members: Dalbey, Ross (Advisor), Sayre, Richard (Advisor).

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Perrine, Z. G. (2010). Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1291063978

Chicago Manual of Style (16^th Edition):

Perrine, Zoee Gokhale. “Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii.” 2010. Doctoral Dissertation, The Ohio State University. Accessed January 29, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1291063978.

MLA Handbook (7^th Edition):

Perrine, Zoee Gokhale. “Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii.” 2010. Web. 29 Jan 2020.

Vancouver:

Perrine ZG. Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii. [Internet] [Doctoral dissertation]. The Ohio State University; 2010. [cited 2020 Jan 29]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291063978.

Council of Science Editors:

Perrine ZG. Modulating Energy and Electron Transfer Processes in Photosystem II of Chlamydomonas reinhardtii. [Doctoral Dissertation]. The Ohio State University; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1291063978

University of Toledo

13. Smith, Megan Schwenker. An Investigation into CaDNA Conformation as a Function of Relative Humidity.

Degree: PhD, Physics, 2010, University of Toledo

URL: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279122399

► Raman spectroscopy experiments on CaDNA free-standing, highly-ordered wet-spun films containing various concentrations of CaCl2 show that CaDNA does not adopt the A conformation and reveals… (more)

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Smith, M. S. (2010). An Investigation into CaDNA Conformation as a Function of Relative Humidity. (Doctoral Dissertation). University of Toledo. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279122399

Chicago Manual of Style (16^th Edition):

Smith, Megan Schwenker. “An Investigation into CaDNA Conformation as a Function of Relative Humidity.” 2010. Doctoral Dissertation, University of Toledo. Accessed January 29, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279122399.

MLA Handbook (7^th Edition):

Smith, Megan Schwenker. “An Investigation into CaDNA Conformation as a Function of Relative Humidity.” 2010. Web. 29 Jan 2020.

Vancouver:

Smith MS. An Investigation into CaDNA Conformation as a Function of Relative Humidity. [Internet] [Doctoral dissertation]. University of Toledo; 2010. [cited 2020 Jan 29]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279122399.

Council of Science Editors:

Smith MS. An Investigation into CaDNA Conformation as a Function of Relative Humidity. [Doctoral Dissertation]. University of Toledo; 2010. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279122399

The Ohio State University

14. Chen, Cai. Quantitative studies of RNA editing and nucleosomal DNA-protein interactions.

Degree: PhD, Biophysics, 2014, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

► We investigate the use of computational methods to study RNA editing and kinetic modeling of protein-nucleic acids interaction. RNA is an important biomolecule that is… (more)

▼ We investigate the use of computational methods to study RNA editing and kinetic modeling of protein-nucleic acids interaction. RNA is an important biomolecule that is deeply involved in almost all aspects of molecular biology. In order to perform such a variety of functions, the primary RNA transcripts need to be extensively processed. One such post-transcriptional event is RNA editing, which alters transcribed RNAs, resulting in RNA products different from the genomically encoded sequence. Altering can occur through the insertion or deletion of nucleotides relative to the original template (indel RNA editing), or via substitution, in which one nucleotide is changed to another. Many types of RNA editing have been observed in different organisms; however, in many instances the mechanisms of RNA editing are not understood at all. The slime mold Physarum polycephalum is a model organism for the study of RNA editing since it has a very high editing rate and editing is highly reliable. However, previous experiments provided very little information about its mechanism. We showed that the combination of two organisms from the Myxomycetes (Physarum polycephalum and Didymium iridis) can provide a better understanding of insertional RNA editing than one organism alone. We find that using the full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium and we predicte several new edited genes in Didymium. By comparing the sequences of the two organisms in the vicinity of the editing sites, we establish minimal requirements for the location of the information by which these editing sites are recognized.While indel RNA editing is well known in several lower species, there was one single report that such insertional editing might exist but there is no independent confirmation. We thus explore the possibility of insertional and deletional RNA editing in human. We apply different computational tools that are capable of identifying indel differences between RNA reads and the matching reference genome. With careful further analysis and filtering, we conclude that indel RNA editing is unlikely to be widespread in human.Adenosine to inosine (A-to-I) editing is involved in a number of neurological diseases and cancer; however, comprehensive understanding of the connection between RNA editing and cancer is lacking. We thus systematically investigate A-to-I RNA editing in the cancer transcriptome and establish a strong link between RNA editing and cancer. We identify a number of differentially edited editing sites between cancer subtypes and normals. Furthermore, we demonstrate that cancer and normal samples and even cancer subtypes can be distinguished based on genome-wide RNA editing profiles alone.All eukaryotic DNA is wrapped around histone proteins to form nucleosomes, which compact DNA to the size needed to fit in the nucleus. Recent single molecule experiments found that transcription factor dissociation rates from target sites within nucleosomes are enhanced by… Advisors/Committee Members: Bundschuh, Ralf (Advisor).

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Chen, C. (2014). Quantitative studies of RNA editing and nucleosomal DNA-protein interactions. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

Chicago Manual of Style (16^th Edition):

Chen, Cai. “Quantitative studies of RNA editing and nucleosomal DNA-protein interactions.” 2014. Doctoral Dissertation, The Ohio State University. Accessed January 29, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347.

MLA Handbook (7^th Edition):

Chen, Cai. “Quantitative studies of RNA editing and nucleosomal DNA-protein interactions.” 2014. Web. 29 Jan 2020.

Vancouver:

Chen C. Quantitative studies of RNA editing and nucleosomal DNA-protein interactions. [Internet] [Doctoral dissertation]. The Ohio State University; 2014. [cited 2020 Jan 29]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347.

Council of Science Editors:

Chen C. Quantitative studies of RNA editing and nucleosomal DNA-protein interactions. [Doctoral Dissertation]. The Ohio State University; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1417523347

University of California, Irvine

15. Plett, Timothy Stephen. Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems.

Degree: 2017, University of California, Irvine

URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10287815

► Lithium ion battery technology has flourished since its introduction into the consumer market. Not only has it helped revolutionize consumer electronics, it also compliments… (more)

▼ Lithium ion battery technology has flourished since its introduction into the consumer market. Not only has it helped revolutionize consumer electronics, it also compliments R&D into clean forms of energy harvest e.g. solar, wind, and hydro-electric. As demand for the technology grows, innovative approaches have been taken to improve capacity, output, and lifetime in Li-ion batteries. The approach studied in this research involves the inclusion of nanostructures, which have the potential to significantly increase capacity. While several techniques to fabricate nanostructures are understood, underlying phenomena governing ion transport in and around these nanostructures is only partially understood, which could directly impact design principles for such devices. This thesis examines a variety of model systems which could serve to simulate environments found in proposed devices and answer questions regarding ion transport phenomena. The main components we studied from such battery systems were electrolyte and cathode materials. The electrolyte experiences different ion transport phenomena arising from the nanoconfinement of the cathode structures both around and inside the electrode material. Thus, having model systems to examine electrolyte and cathode material separately and in tandem is useful for elucidating phenomena without the challenge of deconvolution resulting from other current-carrying mechanisms. Our main tools for carrying out our research were synthetic nanopores. The nanopore structures afforded means to access nanoscale, control environment, and even fabricate components for study. By studying the current-voltage curves in these systems, we were able to draw meaningful conclusions about mechanisms of ion transport in these model systems. The main findings of this research include the inducement of positive surface charge on nanopore structures by organic solvent-based electrolytes by means of dipole and/or ion adsorption, positive evidence of gel electrolyte fitting current models of ion current rectification, and the impact of oxidation state and cycling in cathode material on ion transport through its porous media. Each of these findings is directly related to the thrust of the research and potentially provide insights for future battery design.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Plett, T. S. (2017). Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems. (Thesis). University of California, Irvine. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10287815

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Plett, Timothy Stephen. “Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems.” 2017. Thesis, University of California, Irvine. Accessed January 29, 2020. http://pqdtopen.proquest.com/#viewpdf?dispub=10287815.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Plett, Timothy Stephen. “Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems.” 2017. Web. 29 Jan 2020.

Vancouver:

Plett TS. Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems. [Internet] [Thesis]. University of California, Irvine; 2017. [cited 2020 Jan 29]. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10287815.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Plett TS. Ion Transport Phenomena at the Nanoscale in Different Model Battery Systems. [Thesis]. University of California, Irvine; 2017. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10287815

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

16. Baer, Christina Elizabeth. Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation.

Degree: Biophysics, 2010, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/45v1h1bf

► Mycobacterium tuberculosis (Mtb) coordinates a wide variety of metabolic and cellular responses to changing external environments throughout the multiple stages of infection. Signaling kinases are… (more)

▼ Mycobacterium tuberculosis (Mtb) coordinates a wide variety of metabolic and cellular responses to changing external environments throughout the multiple stages of infection. Signaling kinases are critical for these responses. The Mtb genome encodes 11 Serine/Threonine Protein Kinases (STPKs) that function as important nodes of this sensing and response network, but the chemical and structural changes that mediate kinase activation have not been elucidated. Autophosphorylation activates several of the Mtb STPKs, and kinase dimerization can activate receptor kinases for autophosphorylation through an allosteric dimer interface. Inter-kinase phosphorylation has been reported, but the function and specificity of these interactions remain unknown. In this study, a biochemical approach was used to comprehensively map the cross-kinase trans-phosphorylation activity of the Mtb STPKs. The results reveal a pattern of kinase interactions that suggests each protein plays a distinct regulatory role in controlling cellular processes by phosphorylating other kinases. The PknB and PknH STPKs act in vitro as master regulators that are activated only through autophosphorylation and also phosphorylate other STPKs. In contrast, the signal-transduction kinases PknE, PknJ and PknL are phosphorylated by the master regulatory STPKs and phosphorylate other kinases. The substrate STPKs PknA, PknD, PknF and PknK are phosphorylated by upstream STPKs, but do not phosphorylate other kinases. The delineation of the Mtb STPK signaling networks reveals for the first time the specific network of STPK phosphorylation that may mediate the intracellular signaling circuitry. STPKS are activated and inhibited by phosphorylation at different residues. The regulatory role of the extensive Mtb STPK trans-phosphorylation network is unknown. Through mass spectrophotometry and mutagenesis, the amino acids targeted by each phosphorylation were identified. I find that key activation loop residues are the targets of both autophosphorylation and trans-phosphorylation. Mutation of the two conserved threonines in the activation loops of nine Mtb STPKs renders the kinases inactive. These results demonstrate that activation loop phosphorylation is a common mechanism of Mtb STPK activation. To explore the structural implications of activation loop phosphorylation, I determined the crystal structures of the phosphorylated and unphosphorylated Mtb PknH kinase domain. The PknH kinase domain forms a back-to-back dimer observed previously in the structures of Mtb PknB and PknE. Amino-acid substitutions in the dimer interface fail to block kinase dimerization or autophosphorylation. Unexpectedly, the PknH activation loop is folded in the unphosphorylated form and disordered in the active, phosphorylated enzyme. These structures revealed that the back-to-back kinase dimer is a surprisingly stable structure that does not undergo global conformational changes with phosphorylation or nucleotide binding. Unlike the well-established, conformational regulatory…

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Baer, C. E. (2010). Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/45v1h1bf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Baer, Christina Elizabeth. “Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation.” 2010. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/45v1h1bf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Baer, Christina Elizabeth. “Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation.” 2010. Web. 29 Jan 2020.

Vancouver:

Baer CE. Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation. [Internet] [Thesis]. University of California – Berkeley; 2010. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/45v1h1bf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Baer CE. Mechanisms of Mycobacterium tuberculosis Serine/Threonine Protein Kinase Activation. [Thesis]. University of California – Berkeley; 2010. Available from: http://www.escholarship.org/uc/item/45v1h1bf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

17. Roongthumskul, Yuttana. Mechanical entrainment of saccular hair cell bundles.

Degree: Physics, 2014, UCLA

URL: http://www.escholarship.org/uc/item/9399s6bn

► Mechanical detection of auditory and vestibular system displays exquisite sensitivity, with sub-nanometer detection threshold. The system is also highly nonlinear, exhibiting sharply tuned frequency selectivity… (more)

▼ Mechanical detection of auditory and vestibular system displays exquisite sensitivity, with sub-nanometer detection threshold. The system is also highly nonlinear, exhibiting sharply tuned frequency selectivity and compression of dynamic range. Detection of sounds and vibrations is mediated by the sensory hair cells, which transduce mechanical inputs into electrical signals via hair bundles' deflections. Experiments have consistently shown that hair bundles are not just passive detectors, as they spontaneously oscillate and respond to mechanical stimulus in an active manner. A number of theories based on nonlinear dynamics have described the active hair bundle as a nonlinear system poised near a Hopf bifurcation. Prior studies of mechanical response of hair bundles were done in spontaneously oscillating hair bundles, with mechanical stimulus fluctuating around bundles' resting positions. These conditions, however, might not be true under in vivo conditions. In fact, hair bundles from the bullfrog sacculus are coupled to an overlying membrane, which imposes a steady state offset to the bundle position, and suppresses bundles' spontaneous activity. In this dissertation, we study entrainment of hair bundles from the bullfrog sacculus by sinusoidal stimuli under different mechanical manipulations: offsets and couplings. First, multimode oscillations are more frequently observed upon application of a small negative offset onto spontaneous oscillating hair bundles. Using a numerical model based on detailed physiology of hair bundle, this complex temporal profile requires an additional element - a variable gating spring - with a stiffness that varies with calcium concentration. The dynamics of the process are slow compared to other timescales in the bundle, i.e. gating of transduction channels and slow adaptation process. Second, oscillating hair bundles subject to weak mechanical stimuli are extremely sensitive, with response in the phase histogram already observed at 0.4-pN stimulus. Time-dependent phase-locking behavior at slightly higher signal amplitudes exhibits phase slips, indicating that the system undergoes phase-locking via a SNIC bifurcation. Study of hair bundle dynamics under mechanical offsets reveals a spiking regime, which is even more sensitive to stimulus compared to the oscillatory regime. Larger mechanical offset yields suppression of spontaneous activity, during which spikes can be evoked by stimulus. Evoked spikes occur at a preferred phase of the stimulus cycle, and exhibit a constant amplitude, regardless of signal amplitude and frequency, and leading to an amplifying movement. Finally, we study how coupling between hair bundles affects their mechanical response. Synchronization of bundles' spontaneous movements is always observed, regardless of the original characteristic frequencies of hair bundles prior to coupling. While some coupled bundles show an enhancement, we find that, in general, coupling only two bundles does not significantly improve the sensitivity and frequency tuning.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Roongthumskul, Y. (2014). Mechanical entrainment of saccular hair cell bundles. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/9399s6bn

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Roongthumskul, Yuttana. “Mechanical entrainment of saccular hair cell bundles.” 2014. Thesis, UCLA. Accessed January 29, 2020. http://www.escholarship.org/uc/item/9399s6bn.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Roongthumskul, Yuttana. “Mechanical entrainment of saccular hair cell bundles.” 2014. Web. 29 Jan 2020.

Vancouver:

Roongthumskul Y. Mechanical entrainment of saccular hair cell bundles. [Internet] [Thesis]. UCLA; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/9399s6bn.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Roongthumskul Y. Mechanical entrainment of saccular hair cell bundles. [Thesis]. UCLA; 2014. Available from: http://www.escholarship.org/uc/item/9399s6bn

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

18. Sen, Maya. Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time.

Degree: Chemistry, 2014, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/9m9149j4

► The cell is a fundamental unit of life, and in order for survival, maintaining a stable intracellular enviroment is crucial. ATP-dependent protease complexes regulate protein… (more)

▼ The cell is a fundamental unit of life, and in order for survival, maintaining a stable intracellular enviroment is crucial. ATP-dependent protease complexes regulate protein quality and abundance to ensure homeostasis in the cell. They use chemical energy to power processes necessary for regulating the intracellular environment including protein unfolding, polypeptide translocation, and targeted degradation of abnormal and short-lived regulatory proteins. ClpXP, a well-studied ATP-dependent protease complex from Escherichia coli, is an assembly of homohexameric ClpX coaxially stacked onto a barrel-shaped protease ClpP. ClpX utilizes the energy from ATP hydrolysis to bind the appropriately tagged polypeptide substrates, denature and translocate them into the degradation cavity of ClpP. There have been long-standing questions in the field, specifically whether ClpX can generate force to unfold proteins, how do the six ClpX subunits communicate, and coordinate their ATPases cycles to generate force. Optical tweezers are used as a powerful single-molecule technique to characterize the mechanochemical properties of biomolecules in the nanometer and piconewton range. After a decade of research, we have developed a novel optical tweezers assay to monitor ClpX as it binds, unfolds and translocates various green fluorescent protein (GFP) fusion substrates in real time under a range of ATP concentrations. We characterized the general properties of the motor, which are described in chapter 2. From the analysis of these single-molecule trajectories, we have determined several unique properties of the motor previously undetectable in bulk. First, ClpX can generate up to 20 pN of force to translocate and unfold proteins, eventually being stalled in movement as the opposing force approaches 20 pN. We subsequently explored the communication within the hexameric ring of wild-type ClpX at various ATP, ADP, and Pi concentrations. Our results, described in chapter 3, provided the first direct evidence of a force-generation mechanism and that the phosphate release is coupled to the force-generating step of ClpX. We demonstrated that two to four subunits of the ClpX hexamer actively participates in bursts of translocation and that between the translocation bursts, the motor has a mean constant dwell duration independent of ATP concentration. Our analysis revealed defined a new archetype of motor coordination, which is critical as a fail-safe mechanism to prevent the motor disengagement from its substrate.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sen, M. (2014). Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/9m9149j4

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sen, Maya. “Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time.” 2014. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/9m9149j4.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sen, Maya. “Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time.” 2014. Web. 29 Jan 2020.

Vancouver:

Sen M. Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/9m9149j4.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sen M. Dissecting the molecular mechanisms of the ClpXP protease, one molecule at a time. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/9m9149j4

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Santa Cruz

19. Long, Xi. Single Molecule Studies of Telomere DNA.

Degree: Chemistry, 2014, University of California – Santa Cruz

URL: http://www.escholarship.org/uc/item/7934241b

► Since the discovery by Blackburn in 1978, telomere has been the subject of intense research focus due to its close relationship with aging and cancer.… (more)

▼ Since the discovery by Blackburn in 1978, telomere has been the subject of intense research focus due to its close relationship with aging and cancer. Despite extensive research efforts more than three decades, the structural properties of telomere remain elusive. In this dissertation, I used single molecule techniques to examine the physical properties of telomere. These studies have identified the kinetically favorable telomere G-quadruplex (GQ) structure, revealed the mechanical unfolding pathway of telomere GQ, and characterized the mechanical properties of duplex telomere DNA and the formation of the telomere D-loop. Since the discovery by Blackburn in 1978, the telomere has been the subject of intense research focus due to its close relationship with aging and cancer. Despite extensive research efforts for more than three decades, the structural properties of telomere remain elusive. In this dissertation, I used single molecule techniques to examine the physical properties of telomere. These studies have identified the kinetically favorable telomere G- quadruplex (GQ) structure, revealed the mechanical unfolding pathway of telomere GQ, and characterized the mechanical properties of duplex telomere DNA and the formation of the telomere D-loop. Telomeres are specialize DNA sequence that prevent degradation and aberrant fusion of chromosome ends. The foundation of human telomeres consists of 5-10 kb of duplex TTAGGG repeats follow by a 50 to 200 nucleotides of 3' single stranded overhang. The G-rich single stranded telomere has a propensity to fold into a secondary structure known as GQ. In Chapter 2, single-molecule Förster resonance energy transfer (smFRET) was used for constructing the distribution of telomere DNA GQ conformations under physiological salt conditions. With circular dichroism, the kinetic trapped GQ conformation was discovered. In Chapter 3, smFRET and magnetic tweezers (MT) was used to dissect the folding property telomere GQ. Under stretching force, the unfolding pathway of telomere GQ was characterized by a distance less than 1nm. In Chapter 4, the magnetic tweezers assay revealed that telomere is more resistant to torque-induced denaturation. The direct observation of telomere strand invasion suggested that the stretching force can influence the rate of the invasion and the formation of the telomere displacement loop. The subsequent chapters detail the setup and experimental protocol for the MT-FRET, and describe how to use MT to manipulate DNA. These single molecule assays setup a foundation for investigating the interaction between the telomere and its associated proteins and serve as an experimental platform for telomere drug assessment. Ultimately, with these single molecule assays we will enhance our knowledge on how telomere regulates telomerase activity.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Long, X. (2014). Single Molecule Studies of Telomere DNA. (Thesis). University of California – Santa Cruz. Retrieved from http://www.escholarship.org/uc/item/7934241b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Long, Xi. “Single Molecule Studies of Telomere DNA.” 2014. Thesis, University of California – Santa Cruz. Accessed January 29, 2020. http://www.escholarship.org/uc/item/7934241b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Long, Xi. “Single Molecule Studies of Telomere DNA.” 2014. Web. 29 Jan 2020.

Vancouver:

Long X. Single Molecule Studies of Telomere DNA. [Internet] [Thesis]. University of California – Santa Cruz; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/7934241b.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Long X. Single Molecule Studies of Telomere DNA. [Thesis]. University of California – Santa Cruz; 2014. Available from: http://www.escholarship.org/uc/item/7934241b

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

20. Katira, Shachi. Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems.

Degree: Bioengineering, 2015, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/7jz0t3nh

► Lipid bilayers, along with embedded inclusions such as cholesterol and proteins, constitute a biological membrane—the interface between a cell or organelle and its environment. Understanding… (more)

▼ Lipid bilayers, along with embedded inclusions such as cholesterol and proteins, constitute a biological membrane—the interface between a cell or organelle and its environment. Understanding the structure of a biological membrane and the physical principles responsible for the organization of membrane inclusions is crucial to understanding the processes that occur on the surface of a cell or organelle such as inter-cellular signaling, immune synapse processes, exo- and endocytosis, and membrane fusion. In this work, we study the organization and effect of inclusions in a lipid bilayer using statistical mechanics principles and large-scale molecular simulations.In the first part of this work, we propose a generic physical force for the assembly of inclusions in lipid bilayers—the orderphobic effect. Inspired by modern theories of the hydrophobic effect, this force is governed by the physics of the first-order phase transition between the ordered (i.e., solid-like) and disordered (i.e., fluid) phases of lipid bilayers. We show the existence and nature of this force using coarse-grained molecular dynamics simulations, and demonstrate the lateral assembly of two model proteins, or ‘orderphobes’, within a lipid bilayer. The effect is powerful and operates at nano- to mesoscopic scales, and could be a potential explanation for the clustering of proteins in a biological membrane.In the second part of this work, we focus on hydrophobic inclusions within the lipid bilayer that give rise to organelles known as lipid droplets. These droplets, earlier thought to be passive stores of hydrophobic material in an otherwise aqueous cytosol, have now been implicated in various metabolic diseases. Since the growth and behavior of nascent droplets is sub-microscopic, little is known about the details of this process. We construct a computational framework that allows for a lipid reservoir to study asymmetric inclusions in a lipid bilayer such as the lipid droplet. Further, we identify key stages in the growth and budding of this organelle.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Katira, S. (2015). Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/7jz0t3nh

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Katira, Shachi. “Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems.” 2015. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/7jz0t3nh.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Katira, Shachi. “Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems.” 2015. Web. 29 Jan 2020.

Vancouver:

Katira S. Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems. [Internet] [Thesis]. University of California – Berkeley; 2015. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/7jz0t3nh.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Katira S. Physical Considerations of the Organization of Inclusions in Lipid Bilayer Systems. [Thesis]. University of California – Berkeley; 2015. Available from: http://www.escholarship.org/uc/item/7jz0t3nh

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Riverside

21. Erdemci Tandogan, Gonca. Physics of Viruses: The Role of Genome and Membrane.

Degree: Physics, 2016, University of California – Riverside

URL: http://www.escholarship.org/uc/item/6md8x6zp

► We study the physics of virus assembly. The dissertation can be separated into two parts. The first part focuses on spherical single stranded (ss) RNA… (more)

▼ We study the physics of virus assembly. The dissertation can be separated into two parts. The first part focuses on spherical single stranded (ss) RNA viruses or virus like particles. Using mean-field theory, we explore the role of the secondary structure of RNA on the viral assembly by modeling the RNA as an annealed branched polymer. Our results verify that RNA branchedness maximizes the amount of encapsulated genome into a relatively small capsid and makes assembly more efficient. We furthermore offer an explanation for the phenomena of overcharging observed in viral particles. Chapter 5 demonstrates an application of our theory to satellite tobacco mosaic virus (STMV). Our theory explains, energetically, why a truncated RNA is encapsidated by STMV capsid proteins more favorably.In the second part, we explore the role of genome on the structure of human immunodeficiency virus (HIV) shells (Chapter 6). Our analytical results show that the free energy of confinement of genome into a conical capsid is less than that for a cylindrical one when the genome does not interact with the capsid as in in vivo experiments. This may explain why the conical structures favor over the cylindrical ones in in vivo. In Chapter 7, we carry out coarse-grained simulations to examine the HIV maturation pathways and the role of genome and membrane on the formation of conical shells. We show that the membrane restricts the growth of the otherwise extended incomplete shell and induces local stresses causing formation of the pentamers necessary for the assembly of closed conical or tubular shells. More interestingly, we find that any asymmetry developed in the growing lattice due to interaction with the membrane or genome, or due to the shape of initial immature lattice creates conical capsids, as opposed to cylindrical shells. Furthermore, our work confirms that viruses employ all the accessible pathways to maturation, explaining many aspects of the previous HIV pathway experiments.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

Erdemci Tandogan, G. (2016). Physics of Viruses: The Role of Genome and Membrane. (Thesis). University of California – Riverside. Retrieved from http://www.escholarship.org/uc/item/6md8x6zp

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Erdemci Tandogan, Gonca. “Physics of Viruses: The Role of Genome and Membrane.” 2016. Thesis, University of California – Riverside. Accessed January 29, 2020. http://www.escholarship.org/uc/item/6md8x6zp.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Erdemci Tandogan, Gonca. “Physics of Viruses: The Role of Genome and Membrane.” 2016. Web. 29 Jan 2020.

Vancouver:

Erdemci Tandogan G. Physics of Viruses: The Role of Genome and Membrane. [Internet] [Thesis]. University of California – Riverside; 2016. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/6md8x6zp.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Erdemci Tandogan G. Physics of Viruses: The Role of Genome and Membrane. [Thesis]. University of California – Riverside; 2016. Available from: http://www.escholarship.org/uc/item/6md8x6zp

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

UCLA

22. Zhang, Tracy-Ying. The Nonlinear Dynamics of Coupled Hair Bundles.

Degree: Physics, 2017, UCLA

URL: http://www.escholarship.org/uc/item/81t714rm

► The sensitivity of the auditory system depends in part on the active response of hair cells in the inner ear. Individual hair bundles display frequency… (more)

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, T. (2017). The Nonlinear Dynamics of Coupled Hair Bundles. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/81t714rm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Tracy-Ying. “The Nonlinear Dynamics of Coupled Hair Bundles.” 2017. Thesis, UCLA. Accessed January 29, 2020. http://www.escholarship.org/uc/item/81t714rm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Tracy-Ying. “The Nonlinear Dynamics of Coupled Hair Bundles.” 2017. Web. 29 Jan 2020.

Vancouver:

Zhang T. The Nonlinear Dynamics of Coupled Hair Bundles. [Internet] [Thesis]. UCLA; 2017. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/81t714rm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang T. The Nonlinear Dynamics of Coupled Hair Bundles. [Thesis]. UCLA; 2017. Available from: http://www.escholarship.org/uc/item/81t714rm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

23. Dong, Meimei. Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function.

Degree: Biophysics, 2015, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/2c43v41h

► EphB4 receptor tyrosine kinases bind and cluster with membrane bound ephrinB2 ligands on apposing cells to signal juxtacrine. While this signal activation plays a regulatory… (more)

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dong, M. (2015). Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/2c43v41h

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dong, Meimei. “Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function.” 2015. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/2c43v41h.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dong, Meimei. “Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function.” 2015. Web. 29 Jan 2020.

Vancouver:

Dong M. Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function. [Internet] [Thesis]. University of California – Berkeley; 2015. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/2c43v41h.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dong M. Spatial and Mechanical Regulation of EphB Receptor in Neural Stem Cell Function. [Thesis]. University of California – Berkeley; 2015. Available from: http://www.escholarship.org/uc/item/2c43v41h

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

24. DeWitt, Mark Alan. Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein.

Degree: Biophysics, 2014, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/2hb6m146

► Cytoplasmic dynein is one of the principle motors in eukaryotic cells, responsible for most microtubule (MT) minus end-directed motility and force generation processes, including vesicular… (more)

▼ Cytoplasmic dynein is one of the principle motors in eukaryotic cells, responsible for most microtubule (MT) minus end-directed motility and force generation processes, including vesicular and organelle transport, and mitotic spindle MT organization. Despite being essential to the maintanence of cellular structure in higher eukaryotes, many aspects of dynein's stepping mechanism have remained enigmatic. In this Dissertation, I directly observe several fundamental aspects of dynein's mechanism, and build a strong framework for future studies. I outline in detail the methods for the fluorescent tracking of motor proteins, including advanced two-color and super-resolution techniques. To study cytoplasmic dynein, I developed a two-color fluorescent tracking assay to simultaneously measure the positions of both heads of the motor while it walks along the MT. The results of this experiment clearly show that dynein steps through a unique mechanism: the heads remain widely separated, and do not appear to coordinate with each other to a significant extent. However, the leading head is less likely to take a step at large inter-head separations, indicating some degree of residual coordination remains. I hypothesized that tension along the linker connecting the two heads is the source of this coordination. Using a high-speed two-color assay, I examined the motility of a homodimeric dynein with a flexible linker between the two heads that decreases inter-molecular tension. Despite this alteration, this homodimer has identical stepping and overall motility properties to wild-type dynein, but has reduced coordination, indicating that coordination is dispensable to motility. Coordination could be achieved by gating one of the heads. I investigated gating using a heterodimeric dynein with a wild-type head and an inactive, tightly-bound head. In this heterodimer, we find that the WT head is gated when widely separated from its inactive partner, but becomes un-gated when immediately behind it, indicating that the gating is caused by extension-dependent changes in linker tension as predicted. I next I turned from inter- to intra-molecular communication. Dynein has six distinct AAA subdomains on its motor head, of which only two AAA1 and AAA3, are essential to robust motility. By reducing MT affinity with added salt, I found that AAA3 is required for robust MT release, and that MT release in turn promotes hydrolysis at AAA1. To investigate coordination between AAA1 and AAA3, I analyzed motility in the presence of a slowly-hydrolyzable ATP analog, ATPγS. I found that ATPγS selectively inhibits the AAA3 site. In the presence of saturating analog, the motor can still take long runs of fast motility, indicating that the hydrolysis cycle of AAA3 is much shorter than AAA1. These results show that AAA1 and AAA3 do not coordinate. Instead, AAA3 acts as a "switch" that controls AAA1-directed release from the MT.

Subjects/Keywords: Biophysics

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APA (6^th Edition):

DeWitt, M. A. (2014). Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/2hb6m146

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

DeWitt, Mark Alan. “Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein.” 2014. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/2hb6m146.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

DeWitt, Mark Alan. “Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein.” 2014. Web. 29 Jan 2020.

Vancouver:

DeWitt MA. Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/2hb6m146.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

DeWitt MA. Studies of Inter-and Intra-Molecular Coordination in Cytoplasmic Dynein. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/2hb6m146

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

25. Crow, Alexis Kohnstamm. The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy.

Degree: Biophysics, 2011, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/0dd370j1

► Cells in their native environment are bombarded by mechanical signals ranging from strains within a developing embryo to stiffening of diseased tissue. How these extracellular… (more)

▼ Cells in their native environment are bombarded by mechanical signals ranging from strains within a developing embryo to stiffening of diseased tissue. How these extracellular mechanical signals are converted to biological activity on the cellular scale is a complex and unresolved problem in biology with implications in development and disease. This dissertation focuses on development and implementation of Atomic Force Microscopy (AFM)-based techniques to probe the interactions of cells with the mechanical microenvironment and use of these techniques towards characterizing and explaining the cellular mechanoresponse.We began by integrating a DNA-based adhesion technology with AFM that enables the manipulation of cells by a cantilever without influencing cell viability or signaling. This technique surpasses existing approaches both in the tunability and magnitude of adhesion strength to allow single-cell de-adhesion experiments that measure cell-ligand bonds without cell-surface rupture. The first step in the cellular mechanoresponse is the translation of an extracellular mechanical signal to an intracellular mechanical signal. We used high-resolution three-dimensional multi-particle tracking to measure how local stress applied by an AFM cantilever is propagated through an adherent cell. We observe a distance-dependent propagation on the timescale of seconds and that required an intact cytoskeletal network. This slow stress propagation is consistent with a poroelastic description of the cell that controls the timescales and lengthscales over which external stresses can be transmitted through cells.Recent studies have demonstrated that cells exhibit stiffness-dependent behaviors over long timescales, but the mechanism of how cells sense stiffness over short timescales remains particularly elusive. To study early events in stiffness sensing, we developed a feedback algorithm that enables dynamic and reversible control of the stiffness exposed to a single cell. We employ this stiffness clamp technique to study the contractile response of cells to sudden changes in extracellular stiffness, as defined by the cantilever. We find that the cell contraction rate adapts by accelerating upon a step decrease in stiffness or decelerating upon a step increase, both on a timescale of seconds. This seconds-timescale adaptation is independent of focal adhesion signaling, but it depends strongly on cell contractility suggesting that extracellular stiffness signals are filtered by the viscoelastic cytoskeleton.Together, the techniques described here provide novel and tunable control of the mechanical signals presented to and measured from a single cell with AFM precision. The results obtained using these techniques describe important timescales and considerations towards understanding the cellular mechanoresponse.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Crow, A. K. (2011). The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/0dd370j1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Crow, Alexis Kohnstamm. “The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy.” 2011. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/0dd370j1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Crow, Alexis Kohnstamm. “The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy.” 2011. Web. 29 Jan 2020.

Vancouver:

Crow AK. The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/0dd370j1.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Crow AK. The Cellular Mechanoresponse: Single-Cell Studies by Atomic Force Microscopy. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/0dd370j1

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

26. Weinberger, Ariel. Multi-Strain Virus-Host Dynamics from HIV to Phage.

Degree: Biophysics, 2011, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/4fm794hm

► This dissertation uses mathematical modeling to probe the causes and consequences of multi-strain virus-host coexistence from the applied public health realm in which a second… (more)

▼ This dissertation uses mathematical modeling to probe the causes and consequences of multi-strain virus-host coexistence from the applied public health realm in which a second strain of HIV accelerates human mortality to the basic science realm in which persisting, previously dominant viruses drive the evolution of immunological memory in single-celled Bacteria and Archaea. In both applications, population-scale models are built from the ground up, utilizing experimentally measured parameters of virus and host molecules interacting within a cell to predict how virus and host populations coevolve across time. Model predictions are shown to match time-series data of virus-host dynamics in human hosts in the case of HIV and in prokaryotic hosts in the case of phage. Further, both sets of models generate experimentally testable hypotheses, suggesting therapeutic interventions against two major drivers of human mortality: HIV and pathogenic, antibiotic-resistant bacteria. The first area of application, and the focus of Chapters 2 and 3, is HIV. No one understands why, in about 50% of HIV infections in the West, a more deadly HIV strain emerges late in infection. The new strain, known as X4, differs from its predecessor, known as R5, because X4 only infects CD4+ T cells displaying the receptor CXCR4, while R5 only infects CD4+ T cells displaying the receptor CCR5. Due to the apparent health and anti-HIV immunity of the approximately 10% of Europeans lacking a functional CCR5 receptor, some researchers have touted anti-R5 therapy as an alternative to current anti-HIV drug cocktails. Chapter 2 uses simulations of a novel mathematical model to show how anti-R5 treatment alone may accelerate X4 emergence and resultant immunodeficiency. As an alternative, I show that CCR5 blockers may be more successful in combination with effective HAART therapy or, should they become available, CXCR4 blockers. Chapter 3 probes why X4 only emerges during late-stage HIV infection, showing how X4 persists for many years at low levels, avoiding competitive exclusion to the initially fitter R5 Virus, through X4's unique, low-level infection of naïve CD4+ T cells. In this chapter, I derive a minimal target-cell based model for dual R5, X4 HIV infection in which late-stage switches (bifurcations) to X4 autonomously occur. In this simplified model, an analytic switch condition is probed, allowing us to theoretically predict how different interventions modulate the time to X4 emergence, and providing a compelling explanation for why 50% of Western HIV patients never actually switch to X4 Virus. In Chapter 4, the focus turns to understanding the evolution of adaptive antiviral immunity – such as the T cell immunity targeted by HIV – in its most elemental setting: single-celled prokaryotes possessing the CRISPR immune system. A novel mathematical model of virus-microbe coevolution is derived to understand why prokaryotes with CRISPR-encoded specific immunity conserve old immune sequences for thousands of microbial generations despite compact…

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Weinberger, A. (2011). Multi-Strain Virus-Host Dynamics from HIV to Phage. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/4fm794hm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Weinberger, Ariel. “Multi-Strain Virus-Host Dynamics from HIV to Phage.” 2011. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/4fm794hm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Weinberger, Ariel. “Multi-Strain Virus-Host Dynamics from HIV to Phage.” 2011. Web. 29 Jan 2020.

Vancouver:

Weinberger A. Multi-Strain Virus-Host Dynamics from HIV to Phage. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/4fm794hm.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Weinberger A. Multi-Strain Virus-Host Dynamics from HIV to Phage. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/4fm794hm

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

27. Koulechova, Diana. The Role of Conformational Energetics in Ligand Binding and Thermal Sensation.

Degree: Molecular & Cell Biology, 2014, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/2z65j8wf

► A major outstanding question in protein science is how different regions of a protein communicate with one another. Although we can identify action-at-a-distance phenomena when… (more)

▼ A major outstanding question in protein science is how different regions of a protein communicate with one another. Although we can identify action-at-a-distance phenomena when they occur, a generalized mechanism and an understanding sufficiently thorough as to allow for de novo design remain works in progress. This is particularly true for natively disordered proteins and channel proteins, both of which have traditionally been more technically difficult to characterize biophysically. In this work, I explore the functional relevance of their unique energetics and dynamics.The first project investigates the functional relevance of the hydrophobic core of disordered transcription factor MarA. We randomized the MarA hydrophobic core and selected for variants able to bind the consensus sequence. We find that MarA is highly intolerant of core mutation; this is in contrast to what is seen for the well-folded transcription factor λ-repressor. Furthermore, core variants that do retain the ability to bind consensus sequence have differentially altered affinities for different binding partners. We propose that this can be explained by taking into account the varying energetic impact of these mutations on different MarA conformations and posit that residues distant from the active site can alter both binding affinity and specificity in natively disordered proteins.The second project aims to shed light on the mechanisms of thermosensation. Protein channel TRPA is a heat sensor in rattlesnakes but exhibits no heat-dependent activation in mammals. This discrepancy was mapped to select ankyrin repeats within the protein's cytoplasmic N-terminal domain. We hypothesized that temperature-dependent conformational changes within these repeats propagated to the pore region may be the thermosensing mechanism employed by TRPA1. The isolated repeats were purified and analyzed biophysically. Rattlesnake ankyrin repeats 3-8 are unique in that they do not appear to unfold with temperature on the timescale tested. The mechanism of this remarkable thermotolerance and its physiological relevance are currently under investigation.

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Koulechova, D. (2014). The Role of Conformational Energetics in Ligand Binding and Thermal Sensation. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/2z65j8wf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Koulechova, Diana. “The Role of Conformational Energetics in Ligand Binding and Thermal Sensation.” 2014. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/2z65j8wf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Koulechova, Diana. “The Role of Conformational Energetics in Ligand Binding and Thermal Sensation.” 2014. Web. 29 Jan 2020.

Vancouver:

Koulechova D. The Role of Conformational Energetics in Ligand Binding and Thermal Sensation. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/2z65j8wf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Koulechova D. The Role of Conformational Energetics in Ligand Binding and Thermal Sensation. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/2z65j8wf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

28. Rosen, Laura. Detailed characterization of the earliest events in protein folding.

Degree: Biophysics, 2014, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/5rm0r75g

► A major goal in biology is to understand how the amino acid sequence encodes all aspects of a protein's structure and dynamics. A protein spends… (more)

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rosen, L. (2014). Detailed characterization of the earliest events in protein folding. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/5rm0r75g

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rosen, Laura. “Detailed characterization of the earliest events in protein folding.” 2014. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/5rm0r75g.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rosen, Laura. “Detailed characterization of the earliest events in protein folding.” 2014. Web. 29 Jan 2020.

Vancouver:

Rosen L. Detailed characterization of the earliest events in protein folding. [Internet] [Thesis]. University of California – Berkeley; 2014. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/5rm0r75g.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rosen L. Detailed characterization of the earliest events in protein folding. [Thesis]. University of California – Berkeley; 2014. Available from: http://www.escholarship.org/uc/item/5rm0r75g

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Berkeley

29. Bothma, Jacques. Mechanisms of Transcriptional Precision in the Drosophila Embryo.

Degree: Biophysics, 2013, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/84x1d0pz

► Contemplating how a single cell can turn into the trillions of specialized cells that make a human being staggers the imagination. We still do not… (more)

▼ Contemplating how a single cell can turn into the trillions of specialized cells that make a human being staggers the imagination. We still do not fully understand how the information in a genome is interpreted by a cell to orchestrate this incredible process. One thing that we do know is that much of the complexity we see in the natural world comes down to how essentially the same set of proteins are differentially deployed. One of the key places where this is controlled is at the level of transcription which is the first step in protein production. In this thesis we attempt to shed light on this process by looking at how transcription is regulated in the early Drosophila embryo with a focus on mechanisms of transcriptional precision. We developed imaging and segmentation techniques that allowed for the quantitative visualization of the transcriptional state of thousands of nuclei in the embryo. Using this approach we discovered the phenomenon of repression lag, whereby genes containing large introns are not only slow to be switched on (intron delay), but are also slow to be repressed. Many sequence-specific repressors have been implicated in early development, but the mechanisms by which they silence gene expression have remained elusive. We found that elongating Pol II complexes complete transcription after the onset of repression. As a result, moderately sized genes are fully silenced only after tens of minutes of repression. We propose that this "repression lag" imposes a severe constraint on the regulatory dynamics of embryonic patterning.Having laid the foundations for using quantitative imaging in the early Drosophila embryo we next sought to understand the mechanisms underlying developmental timing, the temporal control of gene expression. Previous studies have provided considerable information about the spatial regulation of gene expression, but there is very little information regarding the temporal coordination of expression. Paused RNA Polymerase (pausd Pol II) is a pervasive feature of Drosophila embryos and mammalian stem cells, but its role in development is uncertain. We demonstrate that there is a spectrum of paused Pol II, which determines the "time to synchrony" the time required to achieve coordinate gene expression across the different cells of a tissue. To determine whether synchronous patterns of gene activation are significant in development, we manipulated the timing of snail expression, which controls the coordinated invagination of 1000 mesoderm cells during gastrulation. Replacement of the strongly paused snail promoter with moderately paused or nonpaused promoters resulted in stochastic activation of snail expression and the progressive loss of mesoderm invagination. Computational modeling of the dorsal-ventral patterning network recapitulated these variable and bistable gastrulation profiles, and emphasized the importance of timing of gene activation in development. We concluded that paused Pol II and transcriptional synchrony are essential for coordinating cell behavior during…

Subjects/Keywords: Biophysics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bothma, J. (2013). Mechanisms of Transcriptional Precision in the Drosophila Embryo. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/84x1d0pz

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bothma, Jacques. “Mechanisms of Transcriptional Precision in the Drosophila Embryo.” 2013. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/84x1d0pz.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bothma, Jacques. “Mechanisms of Transcriptional Precision in the Drosophila Embryo.” 2013. Web. 29 Jan 2020.

Vancouver:

Bothma J. Mechanisms of Transcriptional Precision in the Drosophila Embryo. [Internet] [Thesis]. University of California – Berkeley; 2013. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/84x1d0pz.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bothma J. Mechanisms of Transcriptional Precision in the Drosophila Embryo. [Thesis]. University of California – Berkeley; 2013. Available from: http://www.escholarship.org/uc/item/84x1d0pz

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

30. Dill, Jesse. Struts, springs and crumple zones: protein structures under force.

Degree: Biophysics, 2012, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/69r5s9s3

► In this dissertation, I describe studies on the folding and unfolding of several proteins using a combination of bulk solution spectroscopy and force denaturation experiments… (more)

Subjects/Keywords: Biophysics

10 more images…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dill, J. (2012). Struts, springs and crumple zones: protein structures under force. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/69r5s9s3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dill, Jesse. “Struts, springs and crumple zones: protein structures under force.” 2012. Thesis, University of California – Berkeley. Accessed January 29, 2020. http://www.escholarship.org/uc/item/69r5s9s3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dill, Jesse. “Struts, springs and crumple zones: protein structures under force.” 2012. Web. 29 Jan 2020.

Vancouver:

Dill J. Struts, springs and crumple zones: protein structures under force. [Internet] [Thesis]. University of California – Berkeley; 2012. [cited 2020 Jan 29]. Available from: http://www.escholarship.org/uc/item/69r5s9s3.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dill J. Struts, springs and crumple zones: protein structures under force. [Thesis]. University of California – Berkeley; 2012. Available from: http://www.escholarship.org/uc/item/69r5s9s3

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations