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Description
Diacylglycerol kinase catalyses the ATP-dependent conversion of diacylglycerol to phosphatidic acid in the plasma membrane of Escherichia coli. The small size of this integral membrane trimer, which has 121 residues per subunit, means that available protein must be used economically to craft three catalytic and substrate-binding sites centred about the membrane/cytosol interface. How nature has accomplished this extraordinary feat is revealed here in a crystal structure of the kinase captured as a ternary complex with bound lipid substrate and an ATP analogue. Residues, identified as essential for activity by mutagenesis, decorate the active site and are rationalized by the ternary structure. The γ-phosphate of the ATP analogue is positioned for direct transfer to the primary hydroxyl of the lipid whose acyl chain is in the membrane. A catalytic mechanism for this unique enzyme is proposed. The active site architecture shows clear evidence of having arisen by convergent evolution.
ContributorsLi, Dianfan (Author) / Stansfeld, Phillip J. (Author) / Sansom, Mark S. P. (Author) / Keogh, Aaron (Author) / Vogeley, Lutz (Author) / Howe, Nicole (Author) / Lyons, Joseph A. (Author) / Aragao, David (Author) / Fromme, Petra (Author) / Fromme, Raimund (Author) / Basu, Shibom (Author) / Grotjohann, Ingo (Author) / Kupitz, Christopher (Author) / Rendek, Kimberley (Author) / Weierstall, Uwe (Author) / Zatsepin, Nadia (Author) / Cherezov, Vadim (Author) / Liu, Wei (Author) / Bandaru, Sateesh (Author) / English, Niall J. (Author) / Gati, Cornelius (Author) / Barty, Anton (Author) / Yefanov, Oleksandr (Author) / Chapman, Henry N. (Author) / Diederichs, Kay (Author) / Messerschmidt, Marc (Author) / Boutet, Sebastien (Author) / Williams, Garth J. (Author) / Seibert, M. Marvin (Author) / Caffrey, Martin (Author) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / Department of Physics (Contributor)
Created2015-12-17
Description
Phytochromes are a family of photoreceptors that control light responses of plants, fungi and bacteria. A sequence of structural changes, which is not yet fully understood, leads to activation of an output domain. Time-resolved serial femtosecond crystallography (SFX) can potentially shine light on these conformational changes. Here we report the room temperature crystal structure of the chromophore-binding domains of the Deinococcus radiodurans phytochrome at 2.1 Å resolution. The structure was obtained by serial femtosecond X-ray crystallography from microcrystals at an X-ray free electron laser. We find overall good agreement compared to a crystal structure at 1.35 Å resolution derived from conventional crystallography at cryogenic temperatures, which we also report here. The thioether linkage between chromophore and protein is subject to positional ambiguity at the synchrotron, but is fully resolved with SFX. The study paves the way for time-resolved structural investigations of the phytochrome photocycle with time-resolved SFX.
ContributorsEdlund, Petra (Author) / Takala, Heikki (Author) / Claesson, Elin (Author) / Henry, Leocadie (Author) / Dods, Robert (Author) / Lehtivuori, Heli (Author) / Panman, Matthijs (Author) / Pande, Kanupriya (Author) / White, Thomas (Author) / Nakane, Takanori (Author) / Berntsson, Oskar (Author) / Gustavsson, Emil (Author) / Bath, Petra (Author) / Modi, Vaibhav (Author) / Roy Chowdhury, Shatabdi (Author) / Zook, James (Author) / Berntsen, Peter (Author) / Pandey, Suraj (Author) / Poudyal, Ishwor (Author) / Tenboer, Jason (Author) / Kupitz, Christopher (Author) / Barty, Anton (Author) / Fromme, Petra (Author) / Koralek, Jake D. (Author) / Tanaka, Tomoyuki (Author) / Spence, John (Author) / Liang, Mengning (Author) / Hunter, Mark S. (Author) / Boutet, Sebastien (Author) / Nango, Eriko (Author) / Moffat, Keith (Author) / Groenhof, Gerrit (Author) / Ihalainen, Janne (Author) / Stojkovic, Emina A. (Author) / Schmidt, Marius (Author) / Westenhoff, Sebastian (Author) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / Department of Physics (Contributor)
Created2016-10-19
Description
Serial femtosecond crystallography (SFX) using X-ray free-electron laser sources is an emerging method with considerable potential for time-resolved pump-probe experiments. Here we present a lipidic cubic phase SFX structure of the light-driven proton pump bacteriorhodopsin (bR) to 2.3 Å resolution and a method to investigate protein dynamics with modest sample requirement. Time-resolved SFX (TR-SFX) with a pump-probe delay of 1 ms yields difference Fourier maps compatible with the dark to M state transition of bR. Importantly, the method is very sample efficient and reduces sample consumption to about 1 mg per collected time point. Accumulation of M intermediate within the crystal lattice is confirmed by time-resolved visible absorption spectroscopy. This study provides an important step towards characterizing the complete photocycle dynamics of retinal proteins and demonstrates the feasibility of a sample efficient viscous medium jet for TR-SFX.
ContributorsNogly, Przemyslaw (Author) / Panneels, Valerie (Author) / Nelson, Garrett (Author) / Gati, Cornelius (Author) / Kimura, Tetsunari (Author) / Milne, Christopher (Author) / Milathianaki, Despina (Author) / Kubo, Minoru (Author) / Wu, Wenting (Author) / Conrad, Chelsie (Author) / Coe, Jesse (Author) / Bean, Richard (Author) / Zhao, Yun (Author) / Bath, Petra (Author) / Dods, Robert (Author) / Harimoorthy, Rajiv (Author) / Beyerlein, Kenneth R. (Author) / Rheinberger, Jan (Author) / James, Daniel (Author) / Deponte, Daniel (Author) / Li, Chufeng (Author) / Sala, Leonardo (Author) / Williams, Garth J. (Author) / Hunter, Mark S. (Author) / Koglin, Jason E. (Author) / Berntsen, Peter (Author) / Nango, Eriko (Author) / Iwata, So (Author) / Chapman, Henry N. (Author) / Fromme, Petra (Author) / Frank, Matthias (Author) / Abela, Rafael (Author) / Boutet, Sebastien (Author) / Barty, Anton (Author) / White, Thomas A. (Author) / Weierstall, Uwe (Author) / Spence, John (Author) / Neutze, Richard (Author) / Schertler, Gebhard (Author) / Standfuss, Jorg (Author) / College of Liberal Arts and Sciences (Contributor) / Department of Physics (Contributor) / Department of Chemistry and Biochemistry (Contributor) / Biodesign Institute (Contributor) / Applied Structural Discovery (Contributor) / School of Molecular Sciences (Contributor)
Created2016-08-22
Description
The development of stab-resistant Kevlar armor has been an ongoing field of research
since the late 1990s, with the ultimate goal of improving the multi-threat capabilities of
traditional soft-body armor while significantly improving its protective efficiency - the amount
of layers of armor material required to defeat threats. To create a novel, superior materials
system to reinforce Kevlar armor for the Norica Capstone project, this thesis set out to
synthesize, recover, and characterize zinc oxide nanowire colloids.
The materials synthesized were successfully utilized in the wider Capstone effort to
dramatically enhance the protective abilities of Kevlar, while the data obtained on the 14
hydrothermal synthesis attempts and numerous challenges at recovery provided critical
information on the synthesis parameters involved in the reliable, scalable mass production of the
nanomaterial additive. Additionally, recovery was unconventionally facilitated in the absence of
a vacuum filtration apparatus with nanoscale filters by intentionally inducing electrostatic
agglomeration of the nanowires during standard gravity filtration. The subsequent application of
these nanowires constituted a pioneering use in the production of nanowire-reinforced
STF-based Kevlar coatings, and support the future development and, ultimately, the
commercialization of lighter and more-protective soft armor systems.
since the late 1990s, with the ultimate goal of improving the multi-threat capabilities of
traditional soft-body armor while significantly improving its protective efficiency - the amount
of layers of armor material required to defeat threats. To create a novel, superior materials
system to reinforce Kevlar armor for the Norica Capstone project, this thesis set out to
synthesize, recover, and characterize zinc oxide nanowire colloids.
The materials synthesized were successfully utilized in the wider Capstone effort to
dramatically enhance the protective abilities of Kevlar, while the data obtained on the 14
hydrothermal synthesis attempts and numerous challenges at recovery provided critical
information on the synthesis parameters involved in the reliable, scalable mass production of the
nanomaterial additive. Additionally, recovery was unconventionally facilitated in the absence of
a vacuum filtration apparatus with nanoscale filters by intentionally inducing electrostatic
agglomeration of the nanowires during standard gravity filtration. The subsequent application of
these nanowires constituted a pioneering use in the production of nanowire-reinforced
STF-based Kevlar coatings, and support the future development and, ultimately, the
commercialization of lighter and more-protective soft armor systems.
ContributorsDurso, Michael Nathan (Author) / Tongay, Sefaattin (Thesis director) / Zhuang, Houlong (Committee member) / Materials Science and Engineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Magnetic resonance imaging (MRI) data of metastatic brain cancer patients at the Barrow Neurological Institute sparked interest in the radiology department due to the possibility that tumor size distributions might mimic a power law or an exponential distribution. In order to consider the question regarding the growth trends of metastatic brain tumors, this thesis analyzes the volume measurements of the tumor sizes from the BNI data and attempts to explain such size distributions through mathematical models. More specifically, a basic stochastic cellular automaton model is used and has three-dimensional results that show similar size distributions of those of the BNI data. Results of the models are investigated using the likelihood ratio test suggesting that, when the tumor volumes are measured based on assuming tumor sphericity, the tumor size distributions significantly mimic the power law over an exponential distribution.
ContributorsFreed, Rebecca (Co-author) / Snopko, Morgan (Co-author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / WPC Graduate Programs (Contributor) / School of Accountancy (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Graphene is a very strong two-dimensional material with a lot of potential applications in microelectromechanical systems (MEMS). In this research, graphene is being optimized for use in a 5 m x 5 m graphene resonator. To work properly, this graphene resonator must have a uniform strain across all manufactured devices. To reduce strain induced in graphene sheets grown for use in these resonators, evaporated platinum has been used in this investigation due to its relatively lower surface roughness compared to copper films. The final goal is to have the layer of ultrathin platinum (<=200 nm) deposited on the MEMS graphene resonator and used to grow graphene directly onto the devices to remove the manual transfer step due to its inscalability. After growth, graphene is coated with polymer and the platinum is then etched. This investigation concentrated on the transfer process of graphene onto Si/SiO2 substrate from the platinum films. It was determined that the ideal platinum etchant was aqua regia at a volumetric ratio of 6:3:1 (H2O:HCl:HNO3). This concentration was dilute enough to preserve the polymer and graphene layer, but strong enough to etch within a day. Type and thickness of polymer support layers were also investigated. PMMA at a thickness of 200 nm was ideal because it was easy to remove with acetone and strong enough to support the graphene during the etch process. A reference growth recipe was used in this investigation, but now that the transfer has been demonstrated, growth can be optimized for even thinner films.
ContributorsCayll, David Richard (Author) / Tongay, Sefaattin (Thesis director) / Lee, Hyunglae (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Prostate cancer is the second most common kind of cancer in men. Fortunately, it has a 99% survival rate. To achieve such a survival rate, a variety of aggressive therapies are used to treat prostate cancers that are caught early. Androgen deprivation therapy (ADT) is a therapy that is given in cycles to patients. This study attempted to analyze what factors in a group of 79 patients caused them to stick with or discontinue the treatment. This was done using naïve Bayes classification, a machine-learning algorithm. The usage of this algorithm identified high testosterone as an indicator of a patient persevering with the treatment, but failed to produce statistically significant high rates of prediction.
ContributorsMillea, Timothy Michael (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Solid-state lithium-ion batteries are a major area of research due to their increased safety characteristics over conventional liquid electrolyte batteries. Lithium lanthanum zirconate (LLZO) is a promising garnet-type ceramic for use as a solid-state electrolyte due to its high ionic conductivity. The material exists in two dierent phases, one that is cubic in structure and one that is tetragonal. One potential synthesis method that results in LLZO in the more useful, cubic phase, is electrospinning, where a mat of nanowires is spun and then calcined into LLZO. A phase containing lanthanum zirconate (LZO) and amorphous lithium occursas an intermediate during the calcination process. LZO has been shown to be a sintering aid for LLZO, allowing for lower sintering temperatures. Here it is shown the eects of internal LZO on the sintered pellets. This is done by varying the 700C calcination time to transform diering amounts of LZO and LLZO in electrospun nanowires, and then using the same sintering parameters for each sample. X-ray diraction was used to get structural and compositional analysis of both the calcined powders and sintered pellets. Pellets formed from wires calcined at 1 hour or longer contained only LLZO even if the calcined powder had only undergone the rst phase transformation. The relative density of the pellet with no initial LLZO of 61.0% was higher than that of the pellet with no LZO, which had a relative density of 57.7%. This allows for the same, or slightly higher, quality material to be synthesized with a shorter amount of processing time.
ContributorsLondon, Nathan Harry (Author) / Chan, Candace (Thesis director) / Tongay, Sefaattin (Committee member) / Department of Physics (Contributor) / Materials Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
In the Rare-earth-Tri-telluride family, (RTe3s) [R=La, Ce, Nd, Sm, Gd, Tb, Dy, Er, Ho, Tm] the emergence of Charge Density Waves, (CDW) has been under investigation for a long time due to broadly tunable properties by either chemical substitution or pressure application. These quasi 2D Layered materials RTe3s undergo Fermi Surface Nesting leading to CDW instability. CDWs are electronic instabilities found in low-dimensional materials with highly anisotropic electronic structures. Since the CDW is predominantly driven by Fermi-surface (FS) nesting, it is especially sensitive to pressure-induced changes in the electronic structure. The FS of RTe3s is a function of p-orbitals of Tellurium atoms, which are arranged in two adjacent planes in the crystal structure. Although the FS and electronic structure possess a nearly four-fold symmetry, RTe3s form an incommensurate CDW.This dissertation is structured as follows: Chapter 1 includes basic ideas of Quantum materials, followed by an introduction to CDW and RTe3s. In Chapter 2, there are fundamentals of crystal growth by Chemical Vapor Transport, including various precursors, transport agent, temperature gradient, and rate of the reaction. After the growth, the crystals were confirmed for lattice vibrations by Raman, for composition by Energy Dispersive Spectroscopy; crystal structure and orientation were confirmed by X-ray Diffraction; magnetic ordering was established by Vibrating sample measurement. Detailed CDW study was done on various RTe3s by Raman spectroscopy. The basic mechanism and instrumentations used in these characterizations are explained in Chapter 3. Chapter 4 includes experimental data for crystal growth and results of these characterizations for Parent RTe3s. Chapter 5 includes fundamental insights on Cationic alloying of RTe3s, along with one alloy system’s crystal growth and characterization. This work tries to explain the behavior of CDW by a Temperature-dependent Raman study of RTe3s established the CDW transition temperature accompanied by Phonon softening; Angle-resolved Raman data confirming the nearly four-fold symmetry; thickness-dependent Raman spectroscopy resulting in the conclusion that as thickness decreases CDW transition temperature increases. Also, CDW transition is analyzed as a function of alloying.
ContributorsAttarde, Yashika (Author) / Tongay, Sefaattin (Thesis advisor) / Botana, Antia (Committee member) / Alford, Terry (Committee member) / Arizona State University (Publisher)
Created2021