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Item Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks Involved in the Central Circadian Clock(Frontiers Media Sa, 10/25/16) Park,James; Zhu,Haisun; O'Sullivan,Sean; Ogunnaike,Babatunde A.; Weaver,David P.; Schwaber,James S.; Vadigepalli,Rajanikanth; James Park, Haisun Zhu, Sean O'Sullivan, Babatunde A. Ogunnaike, David R.Weaver , James S. Schwaber and RajanikanthVadigepalli; Ogunnaike, Babatunde A; Schwaber, James S; Vadigepalli, RajanikanthSingle-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we Developmenteloped a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies toward understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.Item Development of Physiologically Based Pharmacokinetic Model (PBPK) of BMP2 in Mice(OMICS Group, 2013) Utturkar, A.; Paul, B.; Akkiraju, H.; Bonor, J.; Dhurjati, Prasad; Nohe, Anja; Utturkar A, Paul B, Akkiraju H, Bonor J, Dhurjati P, Nohe A; Utturkar, A.; Paul, B.; Akkiraju, H.; Bonor, J.; Dhurjati, Prasad; Nohe, AnjaBone Morphogenetic protein 2 holds great promise for potential applications in the clinic. It is a potent growth factor for the use in the cervical spine surgery (FDA approved 2002) and has been marketed as “Infuse” for treating open tibial shaft fractures (FDA approved 2004). However, its use is limited by several significant side effects that maybe due to its potency and effect on different stem cell populations in the spine. BMP2 is expressed throughout the human body in several tissues and at a very high concentration in the blood. BMP receptors, especially BMP receptor type Ia, is ubiquitously expressed in most tissues. Currently, it is difficult to determine how BMP2 is physiologically distributed in mice or humans and no quantitative models are available. A Physiologically-Based Pharmaco-Kinetic (PBPK) model has been developed to determine steady-state distribution of BMP2 in mice. The multi-compartmental PBPK model represents relevant organ/tissues with physiological accuracy. The organs/tissue compartments chosen were brain, lung, heart, liver, pancreas, kidney, uterus, bone and fat. A blood compartment maintained connectivity among the various organs. Four processes characterized the change in the concentration of the protein in every compartment: blood flow in, blood flow out, protein turnover and receptor binding in the organ. The unique aspects of the model are the determination of elimination using receptor kinetics and generation using protein turnover. The model also predicts steady state concentrations of BMP2 in tissues in mice and may be used for possible scale-up of dosage regimens in humans.Item PEG−Polypeptide Block Copolymers as pH-Responsive Endosome- Solubilizing Drug Nanocarriers(American Chemical Society, 2014-05-12) Quadir, Mohiuddin A.; Morton, Stephen W.; Deng, Zhou J.; Shopsowitz, Kevin E.; Murphy, Ryan P.; Epps, Thomas H. III; Hammond, Paula T.; Mohiuddin A. Quadir, Stephen W. Morton, Zhou J. Deng, Kevin E. Shopsowitz, Ryan P. Murphy, Thomas H. Epps, III, and Paula T. Hammond; Murphy, Ryan P.; Epps, Thomas H. IIIHerein we report the potential of click chemistry-modified polypeptide-based block copolymers for the facile fabrication of pH-sensitive nanoscale drug delivery systems. PEG−polypeptide copolymers with pendant amine chains were synthesized by combining N-carboxyanhydridebased ring-opening polymerization with post-functionalization using azide−alkyne cycloaddition. The synthesized block copolymers contain a polypeptide block with amine-functional side groups and were found to self-assemble into stable polymersomes and disassemble in a pH-responsive manner under a range of biologically relevant conditions. The selfassembly of these block copolymers yields nanometer-scale vesicular structures that are able to encapsulate hydrophilic cytotoxic agents like doxorubicin at physiological pH but that fall apart spontaneously at endosomal pH levels after cellular uptake. When drug-encapsulated copolymer assemblies were delivered systemically, significant levels of tumor accumulation were achieved, with efficacy against the triple-negative breast cancer cell line, MDA-MB-468, and suppression of tumor growth in an in vivo mouse model.Item Catch and release: photocleavable cationic diblock copolymers as a potential platform for nucleic acid delivery(Royal Society of Chemistry, 2014-06-05) Green, Matthew D.; Foster, Abbygail A.; Greco, Chad T.; Roy, Raghunath; Lehr, Rachel M.; Epps, Thomas H. III; Sullivan, Millicent O.; Matthew D. Green, Abbygail A. Foster, Chad T. Greco, Raghunath Roy, Rachel M. Lehr, Thomas H. Epps, III and Millicent O. Sullivan; Green, Matthew D.; Foster, Abbygail A.; Greco, Chad T.; Roy, Raghunath; Lehr, Rachel M.; Epps, Thomas H. III; Sullivan, Millicent O.Binding interactions between DNA and cationic nanocarriers must be sufficiently strong to prevent nuclease-mediated degradation, yet weak enough to permit transcription. We demonstrate cationic diblock copolymers containing PEG and o-nitrobenzyl moieties that facilitated tailorable DNA complexation and light-activated release. This design unlocks a new approach to improved non-viral gene packaging.Item Unlocking Chain Exchange in Highly Amphiphilic Block Polymer Micellar Systems: Influence of Agitation(American Chemical Society, 2014-10-14) Murphy, Ryan P.; Kelley, Elizabeth G.; Rogers, Simon A.; Sullivan, Millicent O.; Epps, Thomas H. III; Ryan P. Murphy, Elizabeth G. Kelley, Simon A. Rogers, Millicent O. Sullivan, and Thomas H. Epps, III; Murphy, Ryan P.; Kelley, Elizabeth G.; Rogers, Simon A.; Sullivan, Millicent O.; Epps, Thomas H. IIIChain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene-b-ethylene oxide) or pure poly(butadiene-b-ethylene oxide-d4) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air–water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.Item Determination of Lithium-Ion Distributions in Nanostructured Block Polymer Electrolyte Thin Films by X‑ray Photoelectron Spectroscopy Depth Profiling(American Chemical Society, 2014-12-19) Gilbert, Jonathan B.; Luo, Ming; Shelton, Cameron K.; Rubner, Michael F.; Cohen, Robert E.; Epps, Thomas H. III; Jonathan B. Gilbert, Ming Luo, Cameron K. Shelton, Michael F. Rubner, Robert E. Cohen, and Thomas H. Epps, III; Shelton, Cameron K.; Epps, Thomas H. III; Luo, MingX-ray photoelectron spectroscopy (XPS) depth profiling with C60 þ sputtering was used to resolve the lithium-ion distribution in the nanometer-scale domain structures of block polymer electrolyte thin films. The electrolytes of interest are mixtures of lithium trifluoromethanesulfonate and lamellar-forming polystyrene poly(oligo(oxyethylene)methacrylate) (PS POEM) copolymer. XPS depth profiling results showed that the lithium-ion concentration was directly correlated with the POEM concentration. Furthermore, chemical state and atomic composition of the film were analyzed through the deconvolution of the C1s signal, indicating that the lithium ions appear to be uniformly distributed in the POEM domains. Overall, the unique capabilities of C60 þ depth profiling XPS provide a powerful tool for the analysis of nanostructured polymer thin films in applications ranging from energy storage and generation to surface coatings and nanoscale templates.Item Synthesis and characterization of bicontinuous cubic poly(3,4-ethylene dioxythiophene) gyroid (PEDOT GYR) gels(Royal Society of Chemsitry, 2015-01-12) Cho, Whirang; Wu, Jinghang; Shim, Bong Sup; Kuan, Wei-Fan; Mastroianni, Sarah E.; Young, Wen-Shiue; Kuo, Chin-Chen; Epps, Thomas H. III; Martin, David C.; Whirang Cho, Jinghang Wu, Bong Sup Shim, Wei-Fan Kuan, Sarah E. Mastroianni, Wen-Shiue Young, Chin-Chen Kuo, Thomas H. Epps, III and David C. Martin; Cho, Whirang; Wu, Jinghang; Shim, Bong Sup; Kuan, Wei-Fan; Mastroianni, Sarah E.; Young, Wen-Shiue; Kuo, Chin-Chen; Epps, Thomas H. III; Martin, David C.We describe the synthesis and characterization of bicontinuous cubic poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer gels prepared within lyotropic cubic poly(oxyethylene)10 nonylphenol ether (NP-10) templates with Ia[3 with combining macron]d (gyroid, GYR) symmetry. The chemical polymerization of EDOT monomer in the hydrophobic channels of the NP-10 GYR phase was initiated by AgNO3, a mild oxidant that is activated when exposed to ultraviolet (UV) radiation. The morphology and physical properties of the resulting PEDOT gels were examined as a function of temperature and frequency using optical and electron microscopy, small-angle X-ray scattering (SAXS), dynamic mechanical spectroscopy, and electrochemical impedance spectroscopy (EIS). Microscopy and SAXS results showed that the PEDOT gels remained ordered and stable after the UV-initiated chemical polymerization, confirming the successful templated-synthesis of PEDOT in bicontinuous GYR nanostructures. In comparison to unpolymerized 3,4-ethylenedioxythiophene (EDOT) gel phases, the PEDOT structures had a higher storage modulus, presumably due to the formation of semi-rigid PEDOT-rich nanochannels. Additionally, the storage modulus (G′) for PEDOT gels decreased only modestly with increasing temperature, from ∼1.2 × 105 Pa (10 °C) to ∼7 × 104 Pa (40 °C), whereas G′ for the NP-10 and EDOT gels decreased dramatically, from ∼5.0 × 104 Pa (10 °C) to ∼1.5 × 102 Pa (40 °C). EIS revealed that the impedance of the PEDOT gels was smaller than the impedance of EDOT gels at both high frequencies (PEDOT ∼102 Ω and EDOT 2–3 × 104 Ω at 105 Hz) and low frequencies (PEDOT 103–105 Ω and EDOT ∼5 × 105 Ω at 10−1 Hz). These results indicated that PEDOT gels were highly ordered, mechanically stable and electrically conductive, and thus should be of interest for applications for which such properties are important, including low impedance and compliant coatings for biomedical electrodes.Item Controlled ionic conductivity via tapered block polymer electrolytes(Royal Society of Chemistry, 2015-01-23) Kuan, Wei-Fan; Remy, Roddel; Mackay, Michael E.; Epps, Thomas H. III; Wei-Fan Kuan, Roddel Remy, Michael E. Mackay and Thomas H. Epps, III; Kuan, Wei-Fan; Remy, Roddel; Mackay, Michael E.; Epps, Thomas H. IIIWe present the design of novel solid electrolytes using tapered block polymers (TBPs). In this work, we synthesize a series of TBPs via atom transfer radical polymerization (ATRP) consisting of rigid polystyrene and ion-conducting poly(oligo-oxyethylene methacrylate) segments and explore the role of tapered interfaces on ion transport. Previous studies on TBPs have shown that manipulating the taper composition in block polymers can reduce the unfavorable polymer–polymer interactions between blocks, enabling the design for highly-processable (lower order–disorder transition temperature) polymer electrolytes. Herein, we demonstrate that the taper profile and taper volume fraction significantly impact the glass transition temperatures (Tgs) in block polymer electrolytes, thus affecting the ionic conductivity. Additionally, we find that the normal-tapered materials with z60 vol% tapering exhibit remarkable improvements in ionic conductivity (increase z190% at 20 C and increase z90% at 80 C) in comparison to their non-tapered counterparts. Overall, our TBPs, with controllable interfacial interactions, present an exciting opportunity for the fabrication of cost-effective, highly-efficient, and stable energy storage membranes.Item Manipulating Water in High-Performance Hydroxide Exchange Membrane Fuel Cells through Asymmetric Humidification and Wetproofing(The Electrochemical Society, 2015-02-20) Kaspar, Robert B.; Letterio, Michael P.; Wittkopf, Jarrid A.; Gong, Ke; Gu, Shuang; Yan, Yushan; Robert B. Kaspar, Michael P. Letterio, Jarrid A.Wittkopf, Ke Gong, Shuang Gu and Yushan Yan; Kaspar, Robert B.; Letterio, Michael P.; Wittkopf, Jarrid A.; Gong, Ke; Gu, Shuang; Yan, YushanHydroxide exchange membrane fuel cells (HEMFCs) are an emerging low-cost alternative to conventional proton exchange membrane fuel cells. In addition to producing water at the anode, HEMFCs consume water at the cathode, leading to distinctive water transport behavior. We report that gas diffusion layer (GDL) wetproofing strictly lowers cell performance, but that the penalty is much higher when the anode side is wetproofed compared to the cathode side. We attribute this penalty primarily to mass transport losses from anode flooding, suggesting that cathode humidification may be more beneficial than anode humidification for this device. GDLs with little or no wetproofing perform best, yielding a competitive peak power density of 737 mW cm−2.Item Metal oxide arrays from block copolymer thin film templates(Royal Society of Chemistry, 2015-03-02) Mayeda, Michael K.; Hayat, Jeffery; Epps, Thomas H. III; Lauterbach, Jochen; Michael K. Mayeda, Jeffery Hayat, Thomas H. Epps, III and Jochen Lauterbach; Mayeda, Michael K.; Epps, Thomas H. IIIWe present a simple, though uncommonly used, method to produce versatile, well-ordered, nanoscale arrays of metal oxides such as MgO, Al2O3, TiO2, MnO2, Fe2O3, Co3O4, NiO, CuO, ZnO, ZrO2, RuO2, SnO2, or Ce2 O3 by decoupling metal oxide precursor incorporation from block copolymer (BCP) template formation. In this work, neat BCP thin films were cast and annealed, using standard techniques, to generate templates. The templates were immersed in a precursor solution and formed metal– polymer complexes in one polymer domain. Finally, the organics were removed in an oxidative environment to leave the templated metal oxides. As a concrete example of the method's applicability, we show that the templating method produced ordered TiO2 arrays that exhibited a 13% increase in photocatalytic activity over TiO2 produced by EISA. Furthermore, the addition of gold nanoparticles further improved photocatalytic activity by 43% on our templated TiO2, whereas gold nanoparticles on EISA TiO2 exhibited no improvement. The simplicity and modularity of the templating method makes it amenable to additional applications in catalysis, optics, and sensors.Item RAFT polymerization and associated reactivity ratios of methacrylate-functionalized mixed bio-oil constituents(Royal Society of Chemsitry, 2015-04-22) Holmberg, Angela L.; Karavolias, Michael G.; Epps, Thomas H. III; Angela L. Holmberg, Michael G. Karavolias and Thomas H. Epps, III; Holmberg, Angela L.; Karavolias, Michael G.; Epps, Thomas H. IIIThis work features a new suite of correlations for estimating kinetic parameters from multicomponent reversible addition–fragmentation chain-transfer (RAFT) polymerizations and an improved methodology for determining reactivity ratios in the pursuit of cost-effective and renewable plastics prepared from moderately processed bio-oils. Select monomers representing possible derivatives of compounds found in renewable bio-oils, such as pyrolyzed Kraft lignin and vegetable oils, were polymerized to investigate the consequences of structural diversity on the kinetics of RAFT polymerization. To facilitate predictions of heteropolymer dispersities and molecular weights, apparent chain-transfer coefficients (Capptr's) and propagation rate constants (kappp's) from homopolymerizations were correlated to kinetic parameters associated with the polymerization of bio-oil mixtures. Capptr depended on the reactivity ratios of the bio-oil components and the composition of the bio-oil feed, whereas kappp was related to only the composition of the bio-oil feed. A modified approach for analyzing Mayo–Lewis plots resulted in more accurate reactivity ratios and with greater precision in comparison to conventional nonlinear fitting procedures and traditional linearization fitting methods, respectively. The measured compositional data readily mapped onto the predicted monomer distribution profiles in multicomponent polymers, confirming the validity of the improved method described herein to determine reactivity ratios. Altogether, this manuscript offers a strategy for improving the viability of biobased polymers, addressing two key factors: minimizing separations costs by polymerizing bio-oil mixtures and preventing batch-to-batch inconsistencies in polymer properties by applying a priori knowledge about the bio-oil constituents’ individual kinetic parameters.Item Novel Systems Modeling Methodology in Comparative Microbial Metabolomics: Identifying Key Enzymes and Metabolites Implicated in Autism Spectrum Disorders(MDPI AG, Basel, Switzerland, 2015-04-22) Heberling, Colin; Dhurjati, Prasad; Colin Heberling and Prasad Dhurjati; Heberling, Colin; Dhurjati, PrasadAutism spectrum disorders are a group of mental illnesses highly correlated with gastrointestinal dysfunction. Recent studies have shown that there may be one or more microbial “fingerprints” in terms of the composition characterizing individuals with autism, which could be used for diagnostic purposes. This paper proposes a computational approach whereby metagenomes characteristic of “healthy” and autistic individuals are artificially constructed via genomic information, analyzed for the enzymes coded within, and then these enzymes are compared in detail. This is a text mining application. A custom-designed online application was built and used for the comparative metabolomics study and made publically available. Several of the enzyme-catalyzing reactions involved with the amino acid glutamate were curiously missing from the “autism” microbiome and were coded within almost every organism included in the “control” microbiome. Interestingly, there exists a leading hypothesis regarding autism and glutamate involving a neurological excitation/inhibition imbalance; but the association with this study is unclear. The results included data on the transsulfuration and transmethylation pathways, involved with oxidative stress, also of importance to autism. The results from this study are in alignment with leading hypotheses in the field, which is impressive, considering the purely in silico nature of this study. The present study provides new insight into the complex metabolic interactions underlying autism, and this novel methodology has potential to be useful for developing new hypotheses. However, limitations include sparse genome data availability and conflicting literature experimental data. We believe our software tool and methodology has potential for having great utility as data become more available, comprehensive and reliable.Item Novel Systems Modeling Methodology in Comparative Microbial Metabolomics: Identifying Key Enzymes and Metabolites Implicated in Autism Spectrum Disorders(MDPI AG, 2015-04-22) Heberling, Colin; Dhurjati, Prasad; Colin Heberling, and Prasad Dhurjati.; Heberling, Colin; Dhurjati, PrasadAutism spectrum disorders are a group of mental illnesses highly correlated with gastrointestinal dysfunction. Recent studies have shown that there may be one or more microbial “fingerprints” in terms of the composition characterizing individuals with autism, which could be used for diagnostic purposes. This paper proposes a computational approach whereby metagenomes characteristic of “healthy” and autistic individuals are artificially constructed via genomic information, analyzed for the enzymes coded within, and then these enzymes are compared in detail. This is a text mining application. A custom-designed online application was built and used for the comparative metabolomics study and made publically available. Several of the enzyme-catalyzing reactions involved with the amino acid glutamate were curiously missing from the “autism” microbiome and were coded within almost every organism included in the “control” microbiome. Interestingly, there exists a leading hypothesis regarding autism and glutamate involving a neurological excitation/inhibition imbalance; but the association with this study is unclear. The results included data on the transsulfuration and transmethylation pathways, involved with oxidative stress, also of importance to autism. The results from this study are in alignment with leading hypotheses in the field, which is impressive, considering the purely in silico nature of this study. The present study provides new insight into the complex metabolic interactions underlying autism, and this novel methodology has potential to be useful for developing new hypotheses. However, limitations include sparse genome data availability and conflicting literature experimental data. We believe our software tool and methodology has potential for having great utility as data become more available, comprehensive and reliable.Item Palladium Coated Copper Nanowires as a Hydrogen Oxidation Electrocatalyst in Base(The Electrochemical Society, 2015-05-09) Alia, Shaun M.; Yan, Yushan; Shaun M. Aliaa and Yushan Yan; Alia, Shaun M.Palladium (Pd) nanotubes are synthesized by the spontaneous galvanic displacement of copper (Cu) nanowires, forming extended surface nanostructures highly active for the hydrogen oxidation reaction (HOR) in base. The synthesized catalysts produce specific activities in rotating disk electrode half-cells 20 times greater than Pd nanoparticles and about 80% higher than polycrystalline Pd. Although the surface area of the Pd nanotubes was low compared to conventional catalysts, partial galvanic displacement thrifted the noble metal layer and increased the Pd surface area. The use of Pd coated Cu nanowires resulted in a HOR mass exchange current density 7 times greater than the Pd nanoparticles. The activity of the Pd coated Cu nanowires further nears Pt/C, producing 95% of the mass activity.Item A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation(PLOS (Public Library of Science), 2015-05-21) Zhao, Huaying; Ghirlando, Rodolfo; Alfonso, Carlos; Arisaka, Fumio; Attali, Ilan; Bain, David L.; Bakhtina, Marina M.; Becker, Donald F.; Bedwell, Gregory J.; Bekdemir, Ahmet; Besong, Tabot M. D.; Birck, Catherine; Brautigam, Chad A.; Brennerman, William; Byron, Olwyn; Bzowska, Agnieszka; Chaires, Jonathan B.; Chaton, Catherine T.; Cölfen, Helmut; Connaghan, Keith D.; Crowley, Kimberly A.; Curth, Ute; Daviter, Tina; Dean, William L.; Díez, Ana I.; Ebel, Christine; Eckert, Debra M.; Eisele, Leslie E.; Eisenstein, Edward; England, Patrick; Escalante, Carlos; Fagan, Jeffrey A.; Fairman, Robert; Finn, Ron M.; Fischle, Wolfgang; García de la Torre, José; Gor, Jayesh; Gustafsson, Henning; Hall, Damien; Harding, Stephen E.; Hernández Cifre, José G.; Herr, Andrew B.; Howell, Elizabeth E.; Isaac, Richard S.; Jao, Shu-Chuan; Jose, Davis; Kim, Soon-Jong; Kokona, Bashkim; Kornblatt, Jack A.; Kosek, Dalibor; Krayukhina, Elena; Krzizike, Daniel; Kusznir, Eric A.; Kwon, Hyewon; Larson, Adam; Laue, Thomas M.; Le Roy, Aline; Leech, Andrew P.; Lilie, Hauke; Luger, Karolin; Luque-Ortega, Juan R.; Ma, Jia; May, Carrie A.; Maynard, Ernest L.; Modrak-Wojcik, Anna; Mok, Yee-Foong; Mücke, Norbert; Nagel-Steger, Luitgard; Narlikar, Geeta J.; Noda, Masanori; Nourse, Amanda; Obsil, Tomas; Park, Chad K.; Park, Jin-Ku; Pawelek, Peter D.; Perdue, Erby E.; Perkins, Stephen J.; Perugini, Matthew A.; Peterson, Craig L.; Peverelli, Martin G.; Piszczek, Grzegorz; Prag, Gali; Prevelige, Peter E.; Raynal, Bertrand D. E.; Rezabkova, Lenka; Richter, Klaus; Ringel, Alison E.; Rosenberg, Rose; Rowe, Arthur J.; Rufer, Arne C.; Scott, David J.; Seravalli, Javier G.; Solovyova, Alexandra S.; Song, Renjie; Staunton, David; Stoddard, Caitlin; Stott, Katherine; Strauss, Holger M.; Streicher, Werner W.; Sumida, John P.; Swygert, Sarah G.; Szczepanowski, Roman H.; Tessmer, Ingrid; Toth, Ronald T. IV; Tripathy, Ashutosh; Uchiyama, Susumu; Uebel, Stephan F. W.; Unzai, Satoru; Vitlin Gruber, Anna; von Hippel, Peter H.; Wandrey, Christine; Wang, Szu-Huan; Weitzel, Steven E.; Wielgus-Kutrowska, Beata; Wolberger, Cynthia; Wolff, Martin; Wright, Edward; Wu, Yu-Sung; Wubben, Jacinta M.; Schuck, Peter; Huaying Zhao , Rodolfo Ghirlando , Carlos Alfonso , Fumio Arisaka , Ilan Attali , David L. Bain , Marina M. Bakhtina , Donald F. Becker , Gregory J. Bedwell , Ahmet Bekdemir , Tabot M. D. Besong , Catherine Birck , Chad A. Brautigam , William Brennerman , Olwyn Byron , Agnieszka Bzowska , Jonathan B. Chaires , Catherine T. Chaton , Helmut Cölfen , Keith D. Connaghan , Kimberly A. Crowley , Ute Curth , Tina Daviter , William L. Dean , Ana I. Díez , Christine Ebel , Debra M. Eckert , Leslie E. Eisele , Edward Eisenstein , Patrick England , Carlos Escalante , Jeffrey A. Fagan , Robert Fairman , Ron M. Finn , Wolfgang Fischle , José García de la Torre , Jayesh Gor , Henning Gustafsson , Damien Hall , Stephen E. Harding , José G. Hernández Cifre , Andrew B. Herr , Elizabeth E. Howell , Richard S. Isaac , Shu-Chuan Jao , Davis Jose , Soon-Jong Kim , Bashkim Kokona , Jack A. Kornblatt , Dalibor Kosek , Elena Krayukhina , Daniel Krzizike , Eric A. Kusznir , Hyewon Kwon , Adam Larson , Thomas M. Laue , Aline Le Roy , Andrew P. Leech , Hauke Lilie , Karolin Luger , Juan R. Luque-Ortega , Jia Ma , Carrie A. May , Ernest L. Maynard , Anna Modrak-Wojcik , Yee-Foong Mok , Norbert Mücke , Luitgard Nagel-Steger , Geeta J. Narlikar , Masanori Noda , Amanda Nourse , Tomas Obsil , Chad K. Park , Jin-Ku Park , Peter D. Pawelek , Erby E. Perdue , Stephen J. Perkins , Matthew A. Perugini , Craig L. Peterson , Martin G. Peverelli , Grzegorz Piszczek , Gali Prag , Peter E. Prevelige , Bertrand D. E. Raynal , Lenka Rezabkova , Klaus Richter , Alison E. Ringel , Rose Rosenberg , Arthur J. Rowe , Arne C. Rufer , David J. Scott , Javier G. Seravalli , Alexandra S. Solovyova , Renjie Song , David Staunton , Caitlin Stoddard , Katherine Stott , Holger M. Strauss , Werner W. Streicher , John P. Sumida , Sarah G. Swygert , Roman H. Szczepanowski , Ingrid Tessmer , Ronald T. Toth IV , Ashutosh Tripathy , Susumu Uchiyama , Stephan F. W. Uebel , Satoru Unzai , Anna Vitlin Gruber , Peter H. von Hippel , Christine Wandrey , Szu-Huan Wang , Steven E. Weitzel , Beata Wielgus-Kutrowska , Cynthia Wolberger , Martin Wolff , Edward Wright , Yu-Sung Wu , Jacinta M. Wubben , Peter Schuck; Wu, Yu-SungAnalytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304 ± 0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of ± 0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.Item Design, Operation, Control, and Economics of a Photovoltaic/Fuel Cell/Battery Hybrid Renewable Energy System for Automotive Applications(MDPI AG, 2015-06-09) Whiteman, Zachary S.; Bubna, Piyush; Prasad, Ajay K.; Ogunnaike, Babatunde A.; Zachary S. Whiteman, Piyush Bubna, Ajay K. Prasad and Babatunde A. Ogunnaike; Whiteman, Zachary S.; Bubna, Piyush; Prasad, Ajay K.; Ogunnaike, Babatunde A.Meeting rapidly growing global energy demand—without producing greenhouse gases or further diminishing the availability of non-renewable resources—requires the development of affordable low-emission renewable energy systems. Here, we develop a hybrid renewable energy system (HRES) for automotive applications—specifically, a roof-installed photovoltaic (PV) array combined with a PEM fuel cell/NiCd battery bus currently operating shuttle routes on the University of Delaware campus. The system’s overall operating objectives—meeting the total power demand of the bus and maintaining the desired state of charge (SOC) of the NiCd battery—are achieved with appropriately designed controllers: a logic-based “algebraic controller” and a standard PI controller. The design, implementation, and performance of the hybrid system are demonstrated via simulation of real shuttle runs under various operating conditions. The results show that both control strategies perform equally well in enabling the HRES to meet its objectives under typical operating conditions, and under sudden cloud cover conditions; however, at consistently high bus speeds, battery SOC maintenance is better, and the system consumes less hydrogen, with PI control. An economic analysis of the PV investment necessary to realize the HRES design objectives indicates a return on investment of approximately 30% (a slight, but nonetheless positive, ~$550 profit over the bus lifetime) in Newark, DE, establishing the economic viability of the proposed addition of a PV array to the existing University of Delaware fuel cell/battery bus.Item Complex and extensive post-transcriptional regulation revealed by integrative proteomic and transcriptomic analysis of metabolite stress response in Clostridium acetobutylicum(BioMed Central Ltd., 2015-06-10) Venkataramanan, Keerthi P.; Min, Lie; Hou, Shuyu; Jones, Shawn W.; Ralston, Matthew T.; Lee, Kelvin H.; Papoutsakis, E. Terry; Keerthi P. Venkataramanan, Lie Min, Shuyu Hou, Shawn W. Jones, Matthew T. Ralston, Kelvin H. Lee and E. Terry Papoutsakis; Venkataramanan, Keerthi P.; Min, Lie; Hou, Shuyu; Ralston, Matthew T.; Lee, Kelvin H.; Papoutsakis, E. TerryBACKGROUND: Clostridium acetobutylicum is a model organism for both clostridial biology and solvent production. The organism is exposed to its own toxic metabolites butyrate and butanol, which trigger an adaptive stress response. Integrative analysis of proteomic and RNAseq data may provide novel insights into post-transcriptional regulation. RESULTS: The identified iTRAQ-based quantitative stress proteome is made up of 616 proteins with a 15 % genome coverage. The differentially expressed proteome correlated poorly with the corresponding differential RNAseq transcriptome. Up to 31 % of the differentially expressed proteins under stress displayed patterns opposite to those of the transcriptome, thus suggesting significant post-transcriptional regulation. The differential proteome of the translation machinery suggests that cells employ a different subset of ribosomal proteins under stress. Several highly upregulated proteins but with low mRNA levels possessed mRNAs with long 5'UTRs and strong RBS scores, thus supporting the argument that regulatory elements on the long 5'UTRs control their translation. For example, the oxidative stress response rubrerythrin was upregulated only at the protein level up to 40-fold without significant mRNA changes. We also identified many leaderless transcripts, several displaying different transcriptional start sites, thus suggesting mRNA-trimming mechanisms under stress. Downregulation of Rho and partner proteins pointed to changes in transcriptional elongation and termination under stress. CONCLUSIONS: The integrative proteomic-transcriptomic analysis demonstrated complex expression patterns of a large fraction of the proteome. Such patterns could not have been detected with one or the other omic analyses. Our analysis proposes the involvement of specific molecular mechanisms of post-transcriptional regulation to explain the observed complex stress responseItem Revealing New Structural Insights from Surfactant Micelles through DLS, Microrheology and Raman Spectroscopy(MDPI AG, 2015-06-19) Amin, Samiul; Blake, Steven; Kennel, Rachel C.; Lewis, E. Neil; Samiul Amin, Steven Blake, Rachel C. Kennel and E. Neil Lewis; Kennel, Rachel C.The correlation between molecular changes and microstructural evolution of rheological properties has been demonstrated for the first time in a mixed anionic/zwitterionic surfactant-based wormlike micellar system. Utilizing a novel combination of DLS-microrheology and Raman Spectroscopy, the effect of electrostatic screening on these properties of anionic (SLES) and zwitterionic (CapB) surfactant mixtures was studied by modulating the NaCl concentration. As Raman Spectroscopy delivers information about the molecular structure and DLS-microrheology characterizes viscoelastic properties, the combination of data delivered allows for a deeper understanding of the molecular changes underlying the viscoelastic ones. The high frequency viscoelastic response obtained through DLS-microrheology has shown the persistence of the Maxwell fluid response for low viscosity solutions at high NaCl concentrations. The intensity of the Raman band at 170 cm−1 exhibits very strong correlation with the viscosity variation. As this Raman band is assigned to hydrogen bonding, its variation with NaCl concentration additionally indicates differences in water structuring due to potential microstructural differences at low and high NaCl concentrations. The microstructural differences at low and high NaCl concentrations are further corroborated by persistence of a slow mode at the higher NaCl concentrations as seen through DLS measurements. The study illustrates the utility of the combined DLS, DLS-optical microrheology and Raman Spectroscopy in providing new molecular structural insights into the self-assembly process in complex fluids.Item Permethyl Cobaltocenium (Cp* 2Co+) as an Ultra-Stable Cation for Polymer Hydroxide-Exchange Membranes(Nature Publishing Group, 2015-06-29) Gu, Shuang; Wang, Junhua; Kaspar, Robert B.; Fang, Qianrong; Zhang, Bingzi; Coughlin, E. Bryan; Yan, Yushan; Shuang Gu, Junhua Wang, Robert B. Kaspar, Qianrong Fang, Bingzi Zhang, E. Bryan Coughlin & Yushan Yan; Gu, Shuang; Wang, Junhua; Kspar, Robert B.; Fang, Qianrong; Zhang, Bingzi; Yan, YushanHydroxide (OH−)-exchange membranes (HEMs) are important polymer electrolytes enabling the use of affordable and earth-abundant electrocatalysts for electrochemical energy-conversion devices such as HEM fuel cells, HEM electrolyzers, and HEM solar hydrogen generators. Many HEM cations exist, featuring desirable properties, but new cations are still needed to increase chemical stability at elevated temperatures. Here we introduce the permethyl cobaltocenium [(C5Me5)2Co(III)+ or Cp*2Co+] as an ultra-stable organic cation for polymer HEMs. Compared with the parent cobaltocenium [(C5H5)2Co(III)+ or Cp2Co+], Cp*2Co+ has substantially higher stability and basicity. With polysulfone as an example, we demonstrated the feasibility of covalently linking Cp*2Co+ cation to polymer backbone and prepared Cp*2Co+-functionalized membranes as well. The new cation may be useful in designing more durable HEM electrochemical devices.Item A novel, dynamic pattern-based analysis of NF-κB binding during the priming phase of liver regeneration reveals switch-like functional regulation of target genes(Frontiers Media S.A., 2015-07-07) Cook, Daniel J.; Patra, Biswanath; Kuttippurathu, Lakshmi; Hoek, Jan B.; Vadigepalli, Rajanikanth; Cook, Daniel J.; Vadigepalli, RajanikanthFollowing partial hepatectomy, a coordinated series of molecular events occurs to regulate hepatocyte entry into the cell cycle to recover lost mass. In rats during the first 6 h following resection, hepatocytes are primed by a tightly controlled cytokine response to prepare hepatocytes to begin replication. Although it appears to be a critical element driving regeneration, the cytokine response to resection has not yet been fully characterized. Specifically, the role of one of the key response elements to cytokine signaling (NF-κB) remains incompletely characterized. In this study, we present a novel, genome-wide, pattern-based analysis characterizing NF-κB binding during the priming phase of liver regeneration. We interrogated the dynamic regulation of priming by NF-κB through categorizing NF-κB binding in different temporal profiles: immediate sustained response, early transient response, and delayed response to partial hepatectomy. We then identified functional regulation of NF-κB binding by relating the temporal response profile to differential gene expression. We found that NF-κB bound genes govern negative regulation of cell growth and inflammatory response immediately following hepatectomy. NF-κB also transiently regulates genes responsible for lipid biosynthesis and transport as well as induction of apoptosis following hepatectomy. By the end of the priming phase, NF-κB regulation of genes involved in inflammatory response, negative regulation of cell death, and extracellular structure organization became prominent. These results suggest that NF-κB regulates target genes through binding and unbinding in immediate, transient, and delayed patterns. Such dynamic switch-like patterns of NF-κB binding may govern different functional transitions that drive the onset of regeneration.