Physical Sciences and Mathematics Commons^™

Inhibitors Of Bacterial N-Succinyl-L,L-Diaminopimelic Acid Desuccinylase (Dape) And Demonstration Of In Vitro Antimicrobial Activity, Danuta Gillner, Nicola Armoush, Richard Holz, Daniel Becker

Richard C. Holz

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor L-captopril (IC₅₀ = 3.3 μM, K_i = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli.

Lysine Biosynthesis In Bacteria: A Metallodesuccinylase As A Potential Antimicrobial Target, Danuta Gillner, Daniel P. Becker, Richard C. Holz

Richard C. Holz

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor.

The Fe-Type Nitrile Hydratase From Comamonas Testosteroni Ni1 Does Not Require An Activator Accessory Protein For Expression In Escherichia Coli, Misty Kuhn, Salette Martinez, Natalie Gumataotao, Uwe Bornscheuer, Dali Liu, Richard Holz

Richard C. Holz

We report herein the functional expression of an Fe-type nitrile hydratase (NHase) without the co-expression of an activator protein or the Escherichia coli chaperone proteins GroES/EL. Soluble protein was obtained when the α- and β-subunit genes of the Fe-type NHase Comamonas testosteroni Ni1 (CtNHase) were synthesized with optimized E. coli codon usage and co-expressed. As a control, the Fe-type NHase from Rhodococcus equi TG328–2 (ReNHase) was expressed with (ReNHase+Act) and without (ReNHase−Act) its activator protein, establishing that expression of a fully functional, metallated ReNHase enzyme requires the co-expression of its activator protein, similar to all other Fe-type NHase enzymes reported …

Immobilization Of Motile Bacterial Cells Via Dip-Pen Nanolithography, Dorjderem Nyamjav, Sergey Rozhok, Richard Holz

Richard C. Holz

A strategy to bind bacterial cells to surfaces in a directed fashion via dip-pen nanolithography (DPN) is presented. Cellular attachment to pre-designed DPN generated microarrays was found to be dependent on the shape and size of the surface feature. While this observation is likely due in part to a dense, well formed mercaptohexadecanoic acid (MHA) monolayer generated via DPN, it may also simply be due to the physical shape of the surface structure. Motile Pseudomonas aeruginosa bacterial cells were observed to bind to DPN generated mercaptohexadecanoic acid/poly-L-lysine (MHA/PLL) line patterns, 'blocks' made up of eight lines with 100 nm spacings, …

Structural Characterization Of Zn(Ii)-, Co(Ii)-, And Mn(Ii)-Loaded Forms Of The Arge-Encoded N-Acetyl-L-Ornithine Deacetylase From Escherichia Coli, Ye Tao, Jacob Shokes, Wade Mcgregor, Robert Scott, Richard Holz

Richard C. Holz

The Zn, Co, and Mn K-edge extended X-ray absorption fine structure (EXAFS) spectra of the N-acetyl-l-ornithine deacetylase (ArgE) from Escherichia coli, loaded with one or two equivalents of divalent metal ions (i.e., [Zn(II)_(ArgE)], [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)], [Co(II)Co(II)(ArgE)], [Mn(II)_(ArgE)], and [Mn(II)Mn(II)(ArgE)]), were recorded. The Fourier transformed data (FT) for [Zn(II)_(ArgE)], [Zn(II)Zn(II)(ArgE)], [Co(II)_(ArgE)] and [Co(II)Co(II)(ArgE)] are dominated by a peak at 2.05 Å, that can be fit assuming five or six light atom (N,O) scatterers. Inclusion of multiple-scattering contributions from the outer-shell atoms of a histidine-imidazole ring resulted in reasonable Debye–Waller factors for these contributions and a slight reduction in the goodness-of-fit value …

Synthesis Of N-Succinyl-L,L-Diaminopimelic Acid Mimetics Via Selective Protection, V. Vanek, J. Picha, M. Budesinsky, M. Sanda, J. Jiracek, Richard Holz, J. Hlavacek

Richard C. Holz

The search for potential inhibitors that target so far unexplored bacterial enzyme mono-N-succinyl-L,Ldiaminopimelic acid desuccinylase (DapE) has stimulated a development of methodology for quick and efficient preparation of mono-N-acylated 2,6-diaminopimelic acid (DAP) derivatives bearing the different carboxyl groups or lipophilic moieties on their amino group.

On The Data Of Images, Lori Ziegelmeier

Lori Beth Ziegelmeier

No abstract provided.

Health Professionals’ Roles In Animal Agriculture, Climate Change, And Human Health, Aysha Z. Akhtar, Michael Greger, Hope Ferdowsian, Erica Frank

Michael Greger, MD, FACLM

What we eat is rapidly becoming an issue of global concern. With food shortages, the rise in chronic disease, and global warming, the impact of our dietary choices seems more relevant today than ever. Globally, a transition is taking place toward greater consumption of foods of animal origin, in lieu of plantbased diets. With this transition comes intensification of animal agriculture that in turn is associated with the emergence of zoonotic infectious diseases, environmental degradation, and the epidemics of chronic disease and obesity. Health professionals should be aware of these trends and consider them as they promote healthier and more …

An Abstract View On Modularity In Knowledge Representation, Yuliya Lierler, Miroslaw Truszczyński

Yuliya Lierler

Modularity is an essential aspect of knowledge representation and reasoning theory and practice. It has received substantial attention. We introduce model-based modular systems, an abstract framework for modular knowledge representation formalisms, similar in scope to multi-context systems but employing a simpler information-flow mechanism. We establish the precise relationship between the two frameworks, showing that they can simulate each other. We demonstrate that recently introduced modular knowledge representation formalisms integrating logic programming with satisfiability and, more generally, with constraint satisfaction can be cast as modular systems in our sense. These results show that our formalism offers a simple unifying framework for …

In Service For Sharing: Leadership And Leader - Follower Relationship Factors As Influencers Of Tacit Knowledge Sharing In The It Industry, Billy Whisnant, Odai Khasawneh

Odai Khasawneh

An Unnoticed Consequence Of Szego's Distribution Theorem, William F. Trench

William F. Trench

No abstract provided.

Investigating Mesospheric Gravity Wave Dynamics Over Mcmurdo Station, Antarctica, Jonathan R. Pugmire, Mike J. Taylore, Yucheng Zhao, P Dominique Pautet

Jonathan Pugmire

The ANtarctic Gravity Wave Instrument Network (ANGWIN) is an NSF sponsored international program designed to develop and utilize a network of gravity wave observatories using existing and new instrumentation operated at several established research stations around the continent. The primary goal is to better understand and quantify large-scale gravity wave climatology and their effects on the upper atmosphere over Antarctica. ANGWIN currently comprises research measurements from five nations (U.S., U.K., Australia, Japan, and Brazil) at seven international stations. Utah State University's Atmospheric Imaging Lab operates an all-sky CCD, all-sky infrared imagers and an Advanced Mesospheric Temperature Mapper (AMTM) imager at …

Aspccgtk: Towards Syntactic Parsing With Semantic Disambiguation, Yuliya Lierler, Peter Schueller

Yuliya Lierler

Integration Of Ethics Across The Curriculum: From First Year Through Senior Seminar, Gail E. Gasparich, Larry Wimmers

Gail Gasparich

Amphipathic Co-Oligomers For The Delivery Of Sirna, Christina Cooley, Erika Geihe, Robert Waymouth, Paul Wender

Christina B Cooley

Co-oligomer compounds, complexes of the same with polyanions, such as siRNAs, and methods for using the same are provided. the delivery of polynucleotides, into a cell. The subject co-oligomers include at least a liphopilic monomer and at least a hydrophilic monomer (e.g., a guanidinium containing monomer). In some embodiments, the co-oligomer compounds are capable of complexing a siRNA of interest, thereby increasing the cell permeability of the siRNA, prior to release of the siRNA into the cell. In some embodiments, the subject method is a method of delivery a siRNA into a cell. In some embodiments, the subject method is …

Cutoff: A Spatio-Temporal Imputation Method, Lingbing Feng, Gen Nowak, Terry O'Neill, Alan H. Welsh

Terry O'Neill

A Semi-Analytical Solution For Transient Streaming Potentials Associated With Confined Aquifer Pumping Tests, B. Malama, A. Revil, K. L. Kuhlman

Bwalya Malama

We consider the transient streaming potential response due to pumping from a confined aquifer through a fully penetrating line sink. Confined aquifer flow is assumed to occur without fluid leakage from the confining units. However, since confining units are typically clayey, and hence more electrically conductive than the aquifer, they are treated as non-insulating in our three-layer conceptual model. We develop a semi-analytical solution for the transient streaming potentials response of the aquifer and the confining units to pumping of the aquifer. The solution is fitted to field measurements of streaming potentials associated with an aquifer test performed at a …

Tomography Of The Darcy Velocity From Self-Potential Measurements, A. Jardani, A. Revil, A. Bolève, A. Crespy, J.-P. Dupont, W. Barrash, Bwalya Malama

Bwalya Malama

An algorithm is developed to interpret self-potential (SP) data in terms of distribution of Darcy velocity of the ground water. The model is based on the proportionality existing between the streaming current density and the Darcy velocity. Because the inverse problem of current density determination from SP data is underdetermined, we use Tikhonov regularization with a smoothness constraint based on the differential Laplacian operator and a prior model. The regularization parameter is determined by the L-shape method. The distribution of the Darcy velocity depends on the localization and number of non-polarizing electrodes and information relative to the distribution of the …

The Role Of Transformative Learning In Environmental Education, Jospeh Chen, Akilah Martin

Akilah Martin

Knowledge-based environmental education has been consistently found to be limited in its effectiveness due to its small and indirect role in promoting sustainable behavior, while focusing on the impact of social context has been found to be more conceptually relevant. Transformative learning theory is positioned to be foundational to environmental education based on its increasing focus on promoting social activism through personal transformations. We suggest four criteria in the development of an effective transformative environmental education methodology. Methodologies should (1) focus on change and not just knowledge attainment, (2) reveal behaviors in a real-world context, (3) highlight internal and external …

Free-Standing Inflatable Solar Chimney: Experiment And Theory, Peter Vorobieff, Andrea Mammoli, Nima Fathi, Vakhtang Putkaradze

Nima Fathi

Stilling Basin Performance Analysis By Adv, Seyed Sobhan Aleyasin, Nima Fathi, Peter Vorobieff

Nima Fathi

Exact P-Adic Orders For Differences Of Motzkin Numbers, Tamas Lengyel

Tamas Lengyel

For any prime p, we establish congruences modulo pn+1 for the difference of the pn+1th and pnth Motzkin numbers and determine the p-adic order of the difference. The results confirm recent conjectures on the order. The applied techniques involve the use of congruences for the differences of certain Catalan numbers and binomial coefficients, congruential identities for sums of Catalan numbers, central binomial and trinomial coefficients, infinite incongruent disjoint covering systems and the solution of congruential recurrences.

Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey

Gill Langley, PhD

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Gill Langley, PhD

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses. It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.

Conversion Of Red Fluorescent Protein Into A Bright Blue Probe, Oksana M. Subach, Illia S. Gundorov, Masami Yoshimura, Fedor V. Subach, Jinghang Zhang, David Grunwald, Ekaterina A. Souslova, Dmitriy M. Chudakov, Vladislav V. Verkhusha

David Grünwald

We used a red chromophore formation pathway, in which the anionic red chromophore is formed from the neutral blue intermediate, to suggest a rational design strategy to develop blue fluorescent proteins with a tyrosine-based chromophore. The strategy was applied to red fluorescent proteins of the different genetic backgrounds, such as TagRFP, mCherry, HcRed1, M355NA, and mKeima, which all were converted into blue probes. Further improvement of the blue variant of TagRFP by random mutagenesis resulted in an enhanced monomeric protein, mTagBFP, characterized by the substantially higher brightness, the faster chromophore maturation, and the higher pH stability than blue fluorescent proteins …

Characterization Of The Differentiation And Leptin Secretion Profile Of Adult Stem Cells On Patterned Polylactide Films, Aditya Chaubey, Kevin J. Ross, Malcolm R. Leadbetter, Cheryl T. Gomillion, Karen J.L. Burg

Kevin J. Ross

Several issues need to be better understood before breast tissue engineering becomes a clinically viable option. One of the most important aspects is the interaction between cells and the microtopography of the implant surface. The aim of this study was to evaluate the efficacy of D1 cells, multipotent mouse bone marrow stromal precursors, in differentiating to adipocytes and to characterize their metabolic activity (lactic acid released and glucose consumed), leptin secretion and lipid production when cultured on patterned poly(L-lactide) (PLLA) films. It was determined that, by appropriate stimulation, the D1 cells displayed morphological characteristics of adipocytes and produced lipid. The …

Cefepime Neurotoxicity In An Adolescent Cystic Fibrosis Patient With Aminoglycoside-Induced Acute Kidney Injury, Kristen R. Nichols, Danielle M. Brown, Chad A. Knoderer, Sharon P. Andreoli

Chad A. Knoderer

Objective: To describe a case of cefepime neurotoxicity in an adolescent with cystic fibrosis and aminoglycoside-associated acute kidney injury (AKI). Case Summary: A 15-year-old, 46-kg male with cystic fibrosis (CF) and chronic sinusitis was admitted to the hospital for CF exacerbation. The patient was subsequently discharged to complete home antibiotic therapy with intravenous gentamicin and cefepime. Thirteen days after discharge, while still receiving intravenous antibiotics, the patient presented to an outside hospital complaining of vomiting, fatigue, decreased appetite, and decreased urine output. The patient was diagnosed with AKI and was transferred to our institution, where he displayed signs and symptoms …

Making The Journey From A Traditional Model To An Online Model, Jenny Shrensker, Nazire Koc

Jenny Shrensker

An Approach To Identity Management In Clouds Without Trusted Third Parties, Akram Y. Sarhan, Leszek T. Lilien

Akram YM Sarhan

The management of sensitive data, including identity management (IDM), is an important problem in cloud computing, fundamental for authentication and fine-grained service access control. Our goal is creating an efficient and robust IDM solution that addresses critical issues in cloud computing. The proposed IDM scheme does not rely on trusted third parties (TTPs) or trusted dealers. The scheme is a multiparty interactive solution that combines RSA distributed key generation and attribute-based encryption. We believe that it will be a robust IDM privacy-preserving solution in cloud computing, because it has the following features: (i) protects sensitive data on untrusted hosts using …

Paul Ion Trap As A Diagnostic For Plasma Focus, S.M. Kiai, .. ., Ahmad Talaei, Et Al.

Ahmad Talaei

The plasma discharge contamination by high and low Z Impurities affect the rate of nuclear fusion reaction products, specially when light particles have to be confined. These impurities should be analyzed and can be fairly controlled. This paper reports on the development of a Paul ion trap with ion sources by impact electron ionization as a diagnostic for the 10 kJ Iranian sunshine plasma focus device. Preliminary results of the residual gas are analyzed and presented.