gebhart/patrepeval huggingface dataset:
One‐Bead–One‐Inhibitor–One‐Substrate Screening of Neuraminidase Activity (2005)

Given the eminent threat of a 21st century flu pandemic, the search for novel antiviral compounds is an increasingly important area of research. Recent developments in antiviral research have established the viability of targeting viral neuraminidase (NA), an enzyme that cleaves sialic acid from the cell-surface-mediating passage of the virus in the respiratory tract. N-acetyl neuraminic acid (NeuAc) is the substrate for NA, and analogues of this core structure have been commercialized as antiviral therapeutics. Recent studies have established that this system is well suited for combinatorial approaches to drug discovery. An important step in the process is to develop solid-phase screening technologies. The feasibility of performing competitive solid-phase NA assays is reported herein. Initially, a fluorogenic NeuAc substrate was immobilized on solid support, and the ability of three NAs (Clostridium perfringens, Salmonella typhimurium, and Vibrio cholerae) to cleave the substrate was shown to be analogous to solution-phase assays. The solid support was then bifunctionalized with the fluorogenic NeuAc substrate and one of two known inhibitors (DANA and Zanamivir). The ability of NA to cleave NeuAc from the solid support when simultaneously presented with an inhibitor was shown to be enzyme dependent. As expected, simultaneous presentation of NeuAc and DANA, a nonspecific inhibitor, led to diminished activity for all three enzymes tested. In contrast, dual presentation of NeuAc and the selective inhibitor Zanamivir only showed significant activity against Vibrio cholerae.
Enantio‐ and Diastereoselective Michael Addition Reactions of Unmodified Aldehydes and Ketones with Nitroolefins Catalyzed by a Pyrrolidine Sulfonamide (2006)

Chiral (S)-pyrrolidine trifluoromethanesulfonamide has been shown to serve as an effective catalyst for direct Michael addition reactions of aldehydes and ketones with nitroolefins. A wide range of aldehydes and ketones as Michael donors and nitroolefins as acceptors participate in the process, which proceeds with high levels of enantioselectivity (up to 99 % ee) and diastereoselectivity (up to 50:1 d.r.). The methodology has been employed successfully in an efficient synthesis of the potent H(3) agonist Sch 50917. In addition, a practical three-step procedure for the preparation of (S)-pyrrolidine trifluoromethanesulfonamide has been developed. The high levels of stereochemical control attending Michael addition reactions catalyzed by this pyrrolidine sulfonamide, have been investigated by using ab initio and density functional methods. Transition state structures for the rate-limiting C--C bond-forming step, corresponding to re- and si-face addition to the reactive conformation of the key enamine intermediates have been calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis and that the energy barrier for si-face attack in reactions of aldehydes to form 2R,3S products is lower than that for the re-face attack leading to 2S,3R products. In contrast, the energy barrier for re-face addition is lower than that for si-face addition in reactions of ketones. The computational results, which are in good agreement with the experimental observations, are discussed in the context of the stereochemical course of these Michael addition reactions.
Photonics-on-a-chip: recent advances in integrated waveguides as enabling detection elements for real-world, lab-on-a-chip biosensing applications (2010)

By leveraging advances in semiconductor microfabrication technologies, chip-integrated optical biosensors are poised to make an impact as scalable and multiplexable bioanalytical measurement tools for lab-on-a-chip applications. In particular, waveguide-based optical sensing technology appears to be exceptionally amenable to chip integration and miniaturization, and, as a result, the recent literature is replete with examples of chip-integrated waveguide sensing platforms developed to address a wide range of contemporary analytical challenges. As an overview of the most recent advances within this dynamic field, this review highlights work from the last 2-3 years in the areas of grating-coupled, interferometric, photonic crystal, and microresonator waveguide sensors. With a focus towards device integration, particular emphasis is placed on demonstrations of biosensing using these technologies within microfluidically controlled environments. In addition, examples of multiplexed detection and sensing within complex matrices--important features for real-world applicability--are given special attention.
Electrochromic vanadium–pentoxide–based films: Structural, electrochemical, and optical properties (1995)

Crystalline VO2.5 films were prepared by reactive dc magnetron sputtering followed by annealing posttreatment. Lithium was inserted electrochemically from an electrolyte so that LixVO2.5 (0&amp;lt;x&amp;lt;1.5) was formed. The evolution of the electromotive force (EMF) was recorded during Li intercalation. For lithiated samples, structure by x-ray diffraction, optical properties by spectrophotometry in the 0.3–2.5 μm range, infrared reflectance by spectrophotometry in the 400–1200 cm−1 interval, and the mechanical stress by beam deflectometry were studied. Changes in lattice parameters, phonon spectra, and stress levels gave a consistent picture of the structural evolution. Measurements of optical absorption and EMF were interpreted within a conceptual model of interband transitions between the O 2p band and a split V 3d band. Durability and reversibility of the Li intercalation/deintercalation were verified by potentiodynamic measurements. For comparison, the properties of highly disordered films were also measured.
Toward therapy for DYT1 dystonia: Allele‐specific silencing of mutant TorsinA (2003)

A three-nucleotide (GAG) deletion in the TOR1A gene is the most common cause of inherited dystonia, DYT1. Because the mutant protein, TorsinA (TA), is thought to act in a dominant manner to cause disease, inhibiting expression from the mutant gene represents a potentially powerful therapeutic strategy. In an effort to develop therapy for this disease, we tested whether small interfering RNA (siRNA) could selectively silence expression of mutant TA. Exploiting the three-base pair difference between wild-type and mutant alleles, we designed siRNAs to silence expression of mutant, wild-type, or both forms of TA. In transfected cells, siRNA successfully suppressed wild-type or mutant TA in an allele-specific manner: for example, mutant-specific siRNA reduced the levels of mutant TA to less than 1% of controls with minimal effect on wild-type TA expression. In cells expressing both alleles, thus simulating the heterozygous state, siRNA-mediated suppression remained robust and allele specific. Our siRNA studies demonstrate allele-specific targeting of a dominant neurogenetic disease gene and suggest the broad therapeutic potential of siRNA for DYT1 dystonia and other dominantly inherited neurological diseases.
Antigen Drives Very Low Affinity B Cells to Become Plasmacytes and Enter Germinal Centers (1998)

In the first week of the primary immune response to the (4-hydroxy-3-nitrophenyl)acetyl (NP) hapten, plasmacytic foci and germinal centers (GCs) in C57BL/6 mice are comprised of polyclonal populations of B lymphocytes bearing the lambda1 L-chain (lambda1+). The Ig H-chains of these early populations of B cells are encoded by a variety of VH and D exons undiversified by hypermutation while later, oligoclonal populations are dominated by mutated rearrangements of the VH186.2 and DFL16.1 gene segments. To assess directly Ab affinities within these defined splenic microenvironments, representative VDJ rearrangements were recovered from B cells participating in the early immune response to NP, inserted into Ig H-chain expression cassettes, and transfected into J558L (H-; lambda1+) myeloma cells. These transfectoma Abs expressed a remarkably wide range of measured affinities (Ka = 5 x 10(4)-1.3 x 10(6) M(-1)) for NP. VDJs recovered from both foci and early GCs generated comparable affinities, suggesting that initial differentiation into these compartments occurs stochastically. We conclude that Ag normally activates B cells bearing an unexpectedly wide spectrum of Ab affinities and that this initial, promiscuous clonal activation is followed by affinity-driven competition to determine survival and clonal expansion within GCs and entry into the memory and bone marrow plasmacyte compartments.
Ultra light-sensitive and fast neuronal activation with the Ca2+-permeable channelrhodopsin CatCh (2011)

The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become an important tool in neuroscience, and its use is being considered in therapeutic interventions. Although wild-type and known variant ChR2s are able to drive light-activated spike trains, their use in potential clinical applications is limited by either low light sensitivity or slow channel kinetics. We present a new variant, calcium translocating channelrhodopsin (CatCh), which mediates an accelerated response time and a voltage response that is ~70-fold more light sensitive than that of wild-type ChR2. CatCh's superior properties stem from its enhanced Ca²(+) permeability. An increase in [Ca²(+)](i) elevates the internal surface potential, facilitating activation of voltage-gated Na(+) channels and indirectly increasing light sensitivity. Repolarization following light-stimulation is markedly accelerated by Ca²(+)-dependent BK channel activation. Our results demonstrate a previously unknown principle: shifting permeability from monovalent to divalent cations to increase sensitivity without compromising fast kinetics of neuronal activation. This paves the way for clinical use of light-gated channels.
Learning Neural Network Policies with Guided Policy Search under Unknown Dynamics (2014)

We present a policy search method that uses iteratively refitted local linear models to optimize trajectory distributions for large, continuous problems. These tra-jectory distributions can be used within the framework of guided policy search to learn policies with an arbitrary parameterization. Our method fits time-varying linear dynamics models to speed up learning, but does not rely on learning a global model, which can be difficult when the dynamics are complex and discontinuous. We show that this hybrid approach requires many fewer samples than model-free methods, and can handle complex, nonsmooth dynamics that can pose a challenge for model-based techniques. We present experiments showing that our method can be used to learn complex neural network policies that successfully execute simulated robotic manipulation tasks in partially observed environments with nu-merous contact discontinuities and underactuation. 1
Therapeutic targets in the ASK1-dependent stress signaling pathways (2012)

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.
Get a KISS---communication infrastructure for streaming services in a heterogeneous environment (1998)

Article Free Access Share on Get a KISS—communication infrastructure for streaming services in a heterogeneous environment Authors: K. Jonas German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, Germany German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, GermanyView Profile , M. Kretschmer German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, Germany German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, GermanyView Profile , J. Mödeker German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, Germany German National Research Institute for Information Technology, Schloβ Birlighoven, 53754 St. Augustin, GermanyView Profile Authors Info & Claims MULTIMEDIA '98: Proceedings of the sixth ACM international conference on MultimediaSeptember 1998 Pages 401–410https://doi.org/10.1145/290747.290809Published:01 September 1998Publication History 5citation316DownloadsMetricsTotal Citations5Total Downloads316Last 12 Months21Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Production of Neisseria gonorrhoeae pili (fimbriae) in Pseudomonas aeruginosa (1992)

Pseudomonas aeruginosa K/2PfS, when transformed with an expression plasmid harboring the pilin gene (pilE1) of Neisseria gonorrhoeae MS11, was able to express and assemble gonococcal pilin monomers into surface-associated pili, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and immunoelectron microscopy. Concomitant with the expression of gonococcal pili in P. aeruginosa was the virtual loss of production of P. aeruginosa K/2PfS pili normally associated with the host cell.
Characterization of a Thiol-Ene/Acrylate-Based Polymer for Neuroprosthetic Implants (2017)

Thiol-ene/acrylate shape-memory polymers can be used as base substrates for neural electrodes to treat neurological dysfunction. Neural electrodes are implanted into the body to alter or record impulse conduction. This study characterizes thiol-ene/acrylate polymers to determine which synthesis methods constitute an ideal substrate for neural implants. To achieve a desired <i>T</i><sub>g</sub> between 50 and 56.5 °C, curing conditions, polymer thickness, monomer ratios, and water uptake were all examined and controlled for. Characterization with dynamic mechanical analysis and thermal gravimetric analysis reveals that thin, thiol-ene/acrylate polymers composed of at least 50 mol % acrylate content and cured for at least 1 h at 365 nm are promising as substrates for neural electrodes.
Application of 13C NMR spectroscopy to chemistry of natural glycosides: Rebaudioside-C, a new sweet diterpene glycoside of Stevia rebaudiana. (1977)

From leaves of Stevia rebaudiana BERTONI (Compositae), there were isolated three new sweet glycosides, named rebaudioside-C, -D, and -E. Application of 13C NMR spectroscopy as well as chemical evidences led to assign the structure V in Chart 1 to rebaudioside-C.
Highly Porous Zirconium Metal–Organic Frameworks with β-UH3-like Topology Based on Elongated Tetrahedral Linkers (2016)

Two non-interpenetrated zirconium metal-organic frameworks (Zr-MOFs), NPF-200 and NPF-201, were synthesized via the assembly of elongated tetrahedral linkers with Zr6 and Zr8 clusters. They represent the first examples of MOFs to have the β-UH3-like, 4,12,12T1 topology. Upon activation, NPF-200 exhibits the largest BET surface area (5463 m(2) g(-1)) and void volume (81.6%) among all MOFs formed from tetrahedral ligands. Composed of negative-charged boron-centered tetrahedral linkers, NPF-201 is an anionic Zr-MOF which selectively uptakes photoactive [Ru(bpy)3](2+) for heterogeneous photo-oxidation of thioanisole.
Identification of lncRNA<em> FAM83H-AS1</em> as a novel prognostic marker in luminal subtype breast cancer (2016)

Our study provides a rich resource to the research community for further identifying lncRNAs with diagnostic and therapeutic potentials and exploring biological function of lncRNAs in luminal subtype breast cancer.
Editorial (2001)

his issue of HQ is full of surprises!The editorial board has taken a broad perspective on healthcare this quarter, and has assembled an interesting set of readings that I hope you will enjoy.We begin with an article by Trevor Hancock who is well-known for his passion for healthy communities.Quite rightly, Trevor emphasizes that health is more than health services and that the determinants of health are complex interrelated factors including but not exclusive to wealth, education, the environment and employment.How complicated our healthcare world becomes when we try to fit the role of hospitals in this broader framework.But please keep reminding us, Trevor.We need to address all determinants of health when we create healthy public policy.The theme of the second feature, by Sholom Glouberman, is also the environment.Sholom provides a step-by-step history of the Walkerton affair from 1995 onwards and offers excellent insights and lessons we can all learn from this experience.We conclude with a case study from Cambridge Memorial Hospital -the first hospital in North America to achieve ISO 14001 designation.Next, Anna Day and Leslie MacMillan make the case for implementing a model of hospitalist physicians in acute care hospitals.The plight of the "orphan patient" is on the minds of many people -both those within the system and those on the consumer side.Day and MacMillan describe the role hospitalists might play in easing the tension.They also discuss the steps that will need to be taken to support and sustain the concept.This view is shared by William MacDonald and Lynda Monick at Windsor's Hotel-Dieu Grace Hospital, which implemented a hospitalist system several years ago.Conversely, Kenneth Hook and Jan Kasperski from the Ontario College of Family Physicians offer fiery counter discussion outlining some of the problems with going in the hospitalist direction.In a related topic, what is the real story about the supply of physicians in Canada?John Millar's article, based on CIHI data, sheds some light on this issue.We are delighted to continue our on-going series on nursing issues and the impact on hospitals with a paper from Heather Clarke and her colleagues.This group of nurse researchers is participating in an international research project looking at the quality of the work experience for nurses and its negative or positive impact on nurses' satisfaction with their jobs.The authors also provide a series of strategies to help recruit and retain nurses.We are also pleased to present readers with the regular columns and features they have come to expect in Hospital Quarterly.
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma (2013)

An obstacle to cancer immunotherapy has been that the affinity of T-cell receptors (TCRs) for antigens expressed in tumors is generally low. We initiated clinical testing of engineered T cells expressing an affinity-enhanced TCR against HLA-A*01-restricted MAGE-A3. Open-label protocols to test the TCRs for patients with myeloma and melanoma were initiated. The first two treated patients developed cardiogenic shock and died within a few days of T-cell infusion, events not predicted by preclinical studies of the high-affinity TCRs. Gross findings at autopsy revealed severe myocardial damage, and histopathological analysis revealed T-cell infiltration. No MAGE-A3 expression was detected in heart autopsy tissues. Robust proliferation of the engineered T cells in vivo was documented in both patients. A beating cardiomyocyte culture generated from induced pluripotent stem cells triggered T-cell killing, which was due to recognition of an unrelated peptide derived from the striated muscle-specific protein titin. These patients demonstrate that TCR-engineered T cells can have serious and not readily predictable off-target and organ-specific toxicities and highlight the need for improved methods to define the specificity of engineered TCRs.
GENETIC CONTROL OF NITROGEN ASSIMILATION IN BACTERIA (1982)

Biochemistry and Physiology .. Glutamine Synthetase as Regulator of Gene Expression; the Rise and Fall of a Genetics ot!!:;1:�y;i�� .. :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::: The genes and their products .. Hierarchy oj the regulators .. The complex glnALG operon ...... ; , Respice et pros pice . Genetics of Nitrogen Regulated (Ntr) Systems .. Genetics and Physiology of Enzymes Responsible for Utilization of Ammonia and Glutamine .. NITROGEN REGULATION IN MICROORGANISMS OTHER THAN ENTERIC BACTERIA ..
Roles of Integrins in Human Induced Pluripotent Stem Cell Growth on Matrigel and Vitronectin (2009)

Human induced pluripotent stem cells (iPSCs) hold promise as a source of adult-derived, patient-specific pluripotent cells for use in cell-based regenerative therapies. However, current methods of cell culture are tedious and expensive, and the mechanisms underlying cell proliferation are not understood. In this study, we investigated expression and function of iPSC integrin extracellular matrix receptors to better understand the molecular mechanisms of cell adhesion, survival, and proliferation. We show that iPSC lines generated using Oct-3/4, Sox-2, Nanog, and Lin-28 express a repertoire of integrins similar to that of hESCs, with prominent expression of subunits alpha5, alpha6, alphav, beta1, and beta5. Integrin function was investigated in iPSCs cultured without feeder layers on Matrigel or vitronectin, in comparison to human embryonic stem cells. beta1 integrins were required for adhesion and proliferation on Matrigel, as shown by immunological blockade experiments. On vitronectin, the integrin alphavbeta5 was required for initial attachment, but inhibition of both alphavbeta5 and beta1 was required to significantly decrease iPSC proliferation. Furthermore, iPSCs cultured on vitronectin for 9 passages retained normal karyotype, pluripotency marker expression, and capacity to differentiate in vitro. These studies suggest that vitronectin, or derivatives thereof, might substitute for Matrigel in a more defined system for iPSC culture.
Synthesis of N-Boc-α-amino acids with nucleobase residues as building blocks for the preparation of chiral PNA (peptidic nucleic acids) (1995)

N-Boc-Glutamic acid α-benzyl ester was transformed into 4-bromo-2-(tert-butoxycarbonylamino)-butyric acid benzyl ester using the Barton-Crich protocol. This bromo derivative undergoes nucleophilic substitution with nucleobases to give optically active N-Boc-4-adeninbutyrine (Boc-Aby), N-Boc-4-thyminbutyrine (Boc-Tby), N-Boc-4-guaninbutyrine (Boc-Gby) or N-Boc-4-cytosinbutyrine (Boc-Cby), useful building blocks for the synthesis of chiral peptidic nucleic acids (PNA).