gebhart/patrepeval huggingface dataset:
Discovery of 1‐Hydroxypyridine‐2(1<i>H</i>)‐thione‐6‐carboxylic Acid as a First‐in‐Class Low‐Cytotoxic Nanomolar Metallo β‐Lactamase Inhibitor (2017)

VIM-2 is one of the most common carbapenem-hydrolyzing metallo β-lactamases (MBL) found in many drug-resistant Gram-negative bacterial strains. Currently, there is a lack of effective lead compounds with optimal therapeutic potential within our drug development pipeline. Here we report the discovery of 1-hydroxypyridine-2(1H)-thione-6-carboxylic acid (3) as a first-in-class metallo β-lactamase inhibitor (MBLi) with a potent inhibition K<sub>i</sub> of 13 nm against VIM-2 that corresponds to a remarkable 0.99 ligand efficiency. We further established that 3 can restore the antibiotic activity of amoxicillin against VIM-2-producing E. coli in a whole cell assay with an EC<sub>50</sub> of 110 nm. The potential mode of binding of 3 from molecular modeling provided structural insights that could corroborate the observed changes in the biochemical activities. Finally, 3 possesses a low cytotoxicity (CC<sub>50</sub> ) of 97 μm with a corresponding therapeutic index of 880, making it a promising lead candidate for further optimization in combination antibacterial therapy.
Time-division-multiplexed degenerate optical parametric oscillator for a coherent Ising machine (2015)

We present a large-scale time-division-multiplexed degenerate optical parametric oscillator based on phase-sensitive amplification in a highly-nonlinear fiber for an application to a coherent Ising machine.
Infections Caused by<i>Kluyvera</i>Species in Humans (2001)

Kluyvera is a relatively newly described genus in the family Enterobacteriaceae that infrequently causes infections in humans. The organism has been isolated from various clinical specimens, but its significance has not been clearly established. In fact, it has been regarded alternatively as saprophytic, opportunistic, or pathogenic. Since the redefinition of this genus in 1981, case reports of diverse clinical infections occurring under various host conditions have been published. Here we present a critical review of all Kluyvera infections reported in the literature, along with our experience involving 5 additional cases. Most patients received prompt antimicrobial treatment on the basis of susceptibility testing, and overall the clinical outcomes were good. Antimicrobial agents active against most Kluyvera strains include third-generation cephalosporins, fluoroquinolones, and aminoglycosides. In contrast, the resistance to ampicillin, extended-spectrum penicillins, and first- and second-generation cephalosporins is significant. Kluyvera is a potentially virulent pathogen that deserves aggressive treatment designed with an awareness of the organism's antimicrobial resistance patterns.
Dynamically adapting GUIs to diverse input devices (2006)

Many of today's desktop applications are designed for use with a pointing device and keyboard. Someone with a disability, or in a unique environment, may not be able to use one or both of these devices. We have developed an approach for automatically modifying desktop applications to accommodate a variety of input alternatives as well as a demonstration implementation, the Input Adapter Tool (IAT). Our work is differentiated from past work by our focus on input adaptation (such as adapting a paint program to work without a pointing device) rather than output adaptation (such as adapting web pages to work on a cellphone). We present an analysis showing how different common interactive elements and navigation techniques can be adapted to specific input modalities. We also describe IAT, which supports a subset of these adaptations, and illustrate how it adapts different inputs to two applications, a paint program and a form entry program.
Gossip: harmless fun or malevolent presence? (2011)

There is a saying that goes something like: ‘the one thing worse than being gossiped about is not being gossiped about at all’ and the wealth of gossip magazines, television shows and celebrity ‘blogs’ would certainly demonstrate that gossip is a multi-billion dollar industry, certainly within the world of ‘celebrity’ and entertainment. Indeed one man, Perez Hilton, has risen from obscurity and gained celebrity status and a net worth in excess of $30 million for creating a ‘celebrity blog’. This article considers the forms gossip may take and the role it has and does play in society.
Humanized Mouse Models for Human Immunodeficiency Virus Infection (2017)

Human immunodeficiency virus (HIV) remains a significant source of morbidity and mortality worldwide. No effective vaccine is available to prevent HIV transmission, and although antiretroviral therapy can prevent disease progression, it does not cure HIV infection. Substantial effort is therefore currently directed toward basic research on HIV pathogenesis and persistence and developing methods to stop the spread of the HIV epidemic and cure those individuals already infected with HIV. Humanized mice are versatile tools for the study of HIV and its interaction with the human immune system. These models generally consist of immunodeficient mice transplanted with human cells or reconstituted with a near-complete human immune system. Here, we describe the major humanized mouse models currently in use, and some recent advances that have been made in HIV research/therapeutics using these models.
Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies (2019)

CSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease 'activity' rather than as a marker of disability or disease stage.
Remodeling of Human Plasma Lipoproteins by Detergent Perturbation (2005)

Detergent perturbation, the treatment of total human plasma lipoproteins (TLP) with sodium cholate and its subsequent removal, has been used to study lipoprotein dynamics and stability. At physiological TLP concentrations, detergent perturbation converts low-density lipoproteins (LDL) and high-density lipoproteins (HDL) to higher-particle weight species with the concomitant release of apo A-I but not apo A-II as a lipid-poor species. Detergent perturbation of isolated HDL also releases lipid-poor apo A-I and forms larger HDL species, whereas detergent perturbation of an isolated LDL has no effect on its size. A model is presented in which detergent perturbation induces transfer of PC from metastable HDL and LDL to mixed micelles with sodium cholate. The remaining LDL and HDL are unstable because of the loss of their surface components, phospholipid and/or apo A-I, and fuse to give larger LDL and HDL particles. These effects on HDL, i.e., PC transfer, apo A-I dissociation, and particle fusion, emulate the activity of human plasma phospholipid transfer protein. Thus, detergent perturbation is a new and potentially powerful method for determining lipoprotein stability, studying the mechanisms for remodeling of plasma lipoproteins, and preparing new forms of HDL and LDL with unique interactions with lipoprotein transporters and receptors.
Thiol-Epoxy “Click” Chemistry to Engineer Cytocompatible PEG-Based Hydrogel for siRNA-Mediated Osteogenesis of hMSCs (2018)

Thiol-epoxy "click" chemistry is employed for the first time to engineer a new cytocompatible PEG-based hydrogel system in aqueous media with the ability to encapsulate human mesenchymal stem cells (hMSCs) and control their fate for tissue regeneration. Cells were easily encapsulated into the hydrogels and exhibited high cell viability over 4 weeks of culture regardless of the presence of siRNA, complexed with polyethylenimine (PEI) in the form of siRNA/PEI nanocomplexes, indicating the biocompatibility of the developed hydrogel. Loading pro-osteogenic siNoggin in the hydrogel significantly enhanced the osteogenesis of encapsulated hMSCs, demonstrating the potential application of this system in tissue engineering.
The T Cell-Dependent B Cell Immune Response and Germinal Center Reaction Are Intact in A-myb-Deficient Mice (2001)

Expression of the protooncogene A-myb is restricted to the developing CNS, adult testes, breasts in late pregnancy, and germinal centers of secondary B cell follicles. The functional relevance of A-myb expression at three of these sites has been demonstrated previously via the generation and analysis of A-myb-deficient mice, which display behavioral abnormalities, male sterility, and perturbed breast development during pregnancy. In contrast, here we show that the germinal center response driven by T cell-dependent Ag immunization and the associated processes of Ab V gene somatic hypermutation, affinity maturation, and heavy chain class switching are overtly normal in A-myb-deficient mice. Nonetheless, these mice display mild splenic white pulp hypoplasia and blunted primary serum Ab responses, suggesting that although A-myb is not directly involved in the regulation of the memory B cell response, it may play a role in enhancing peripheral B cell survival or proliferative capacity.
Topical Anti-inflammatory Activity of Eupatilin, A Lipophilic Flavonoid from Mountain Wormwood (Artemisia umbelliformis Lam.) (2009)

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the major lipophilic flavonoid from Artemisia umbelliformis Lam. and Artemisia genipi Weber, two mountain wormwoods used for the production of the celebrated alpine liqueur genepy. The topical anti-inflammatory activity of eupatilin was investigated using the inhibition of the Croton-oil-induced dermatitis in the mouse ear as the end point. The oedematous response and the leukocyte infiltration were evaluated up to 48 h after the induction of phlogosis, comparing eupatilin with hydrocortisone and indomethacin as representatives of steroid and non-steroid anti-inflammatory drugs, respectively. At maximum development, eupatilin significantly reduced edema in a dose-dependent manner (ID(50) = 0.28 micromol/cm(2)), showing an anti-inflammatory potency comparable to that of indomethacin (ID(50) = 0.26 micromol/cm(2)) and only 1 order of magnitude lower than that of hydrocortisone (ID(50) = 0.03 micromol/cm(2)). Within 48 h, eupatilin (0.30 micromol/cm(2)) caused a global inhibition of the oedematous response (42%) higher than that of an equimolar dose of indomethacin (18%) and fully comparable to that of 0.03 micromol/cm(2) of hydrocortisone (55%). Moreover, the effect of eupatilin on the granulocytes infiltrate (32% inhibition) was similar to that of indomethacin (35% inhibition) and comparable to that of hydrocortisone (42% reduction), as confirmed by histological analysis. When our results are taken together, they show that eupatilin is endowed with potent in vivo topical anti-inflammatory activity, qualitatively similar to that of hydrocortisone and intermediate in terms of potency between those of steroid and non-steroid drugs.
The GalNAc-type O-Glycoproteome of CHO Cells Characterized by the SimpleCell Strategy (2014)

The Chinese hamster ovary cell (CHO) is the major host cell factory for recombinant production of biological therapeutics primarily because of its "human-like" glycosylation features. CHO is used for production of several O-glycoprotein therapeutics including erythropoietin, coagulation factors, and chimeric receptor IgG1-Fc-fusion proteins, however, some O-glycoproteins are not produced efficiently in CHO. We have previously shown that the capacity for O-glycosylation of proteins can be one limiting parameter for production of active proteins in CHO. Although the capacity of CHO for biosynthesis of glycan structures (glycostructures) on glycoproteins are well established, our knowledge of the capacity of CHO cells for attaching GalNAc-type O-glycans to proteins (glycosites) is minimal. This type of O-glycosylation is one of the most abundant forms of glycosylation, and it is differentially regulated in cells by expression of a subset of homologous polypeptide GalNAc-transferases. Here, we have genetically engineered CHO cells to produce homogeneous truncated O-glycans, so-called SimpleCells, which enabled lectin enrichment of O-glycoproteins and characterization of the O-glycoproteome. We identified 738 O-glycoproteins (1548 O-glycosites) in cell lysates and secretomes providing the first comprehensive insight into the O-glycosylation capacity of CHO (http://glycomics.ku.dk/o-glycoproteome_db/).
Piezoelectric Immunosensors - Theory and Applications (1999)

ABSTRACT ABSTRACT A Mini Review of recent advances in piezoelectric immunobiosensors is presented. First a review of the theory and history of the technique is given, followed by a critical survey of the use of this method in various fields of analysis. Keywords:: Piezoelectric ImmunosensorsBiosensorsQuartz CrystalsQCMImmunologyDetectionAirLiquid Assays
A Basic Primer on Data Mining (2002)

Abstract Just as gold mining is a process for sifting through loads of ore to find valuable nuggets, data mining is a process for sifting through massive amounts of data to find information useful for optimizing business decision making and operations. Although interest in data mining is growing, many IT professionals and business managers may not have more than a passing exposure to the term. the purpose of this paper is to provide an introductory tutorial on the topic of data mining. Included are a brief description of data mining methods, a review of data mining software tools, and a survey of examples of data mining applications.
Understanding Hidden Memories of Recurrent Neural Networks (2017)

Recurrent neural networks (RNNs) have been successfully applied to various natural language processing (NLP) tasks and achieved better results than conventional methods. However, the lack of understanding of the mechanisms behind their effectiveness limits further improvements on their architectures. In this paper, we present a visual analytics method for understanding and comparing RNN models for NLP tasks. We propose a technique to explain the function of individual hidden state units based on their expected response to input texts. We then co-cluster hidden state units and words based on the expected response and visualize co-clustering results as memory chips and word clouds to provide more structured knowledge on RNNs' hidden states. We also propose a glyph-based sequence visualization based on aggregate information to analyze the behavior of an RNN's hidden state at the sentence-level. The usability and effectiveness of our method are demonstrated through case studies and reviews from domain experts.
Reduction of Salivary Bacteria by Pre‐Procedural Rinses With Chlorhexidine 0.12% (1991)

The purpose of this study was to assess the effect of pre-procedural rinsing (2 consecutive rinses) with 0.12% chlorhexidine gluconate (CHX) on salivary bacteria during scaling and root planing procedures (S&RP). Because blood and debris arising from S&RP could inactivate CHX and decrease its antimicrobial effect, patients were evaluated throughout their appointment. Forty subjects rinsed with either 15 ml of CHX rinse or control (sterile water) for 30 seconds, expectorated and immediately rinsed again for 30 seconds. Unstimulated saliva samples were obtained at baseline (immediately before rinsing), and at 1 minute, 30 minutes, and 60 minutes after baseline. All 30 and 60 minute samples contained visible blood and debris. Samples were immediately diluted in transport fluid containing a CHX-neutralizer and then plated on trypticase soy agar for enumeration of the total aerobic and facultative bacterial load. The dual rinses with 0.12% CHX immediately reduced the salivary bacterial load 97% and this reduction persisted for 60 minutes during S&RP. At 30 minutes and at 60 minutes aerobic bacteria were reduced 77% compared to control, and 96% compared to baseline. CHX was not inactivated by the high organic load (blood and debris) present during the procedure. Pre-procedural rinsing with CHX has a profound and sustained effect on the aerobic and facultative flora of the oral cavity, which may contribute to a variety of clinical benefits. Pre-procedural rinsing may also be of value in protecting patients and dental professionals during dental manipulations.
Regulation of mitotic recombination between DNA repeats in centromeres (2017)

Centromeres that are essential for faithful segregation of chromosomes consist of unique DNA repeats in many eukaryotes. Although recombination is under-represented around centromeres during meiosis, little is known about recombination between centromere repeats in mitotic cells. Here, we compared spontaneous recombination that occurs between ade6B/ade6X inverted repeats integrated at centromere 1 (cen1) or at a non-centromeric ura4 locus in fission yeast. Remarkably, distinct mechanisms of homologous recombination (HR) were observed in centromere and non-centromere regions. Rad51-dependent HR that requires Rad51, Rad54 and Rad52 was predominant in the centromere, whereas Rad51-independent HR that requires Rad52 also occurred in the arm region. Crossovers between inverted repeats (i.e. inversions) were under-represented in the centromere as compared to the arm region. While heterochromatin was dispensable, Mhf1/CENP-S, Mhf2/CENP-X histone-fold proteins and Fml1/FANCM helicase were required to suppress crossovers. Furthermore, Mhf1 and Fml1 were found to prevent gross chromosomal rearrangements mediated by centromere repeats. These data for the first time uncovered the regulation of mitotic recombination between DNA repeats in centromeres and its physiological role in maintaining genome integrity.
Use of wood fibers in thermoplastics. VII. The effect of coupling agents in polyethylene–wood fiber composites (1989)

Abstract Linear low density polyethylene (LLDPE) was reinforced with different wood fibers, aspen chemithermomechanical pulp (bleached and unbleached), and other commerical wood pulps. Silane coupling agents A‐172, A‐174, A‐1100, and polymethylene polyphenyl isocyanate were used to improve the bonding between the fiber and matrix. LLDPE filled with pretreated wood fiber produced a significant improvement in tensile strength and modulus. Comparison of tensile and impact properties of wood fiber composites with mica and glass fiber composites shows the potential advantage (in terms of material cost and specific properties) of wood fiber as a reinforcement.
Regulation of Secondary Cell Wall Development by Cortical Microtubules during Tracheary Element Differentiation in Arabidopsis Cell Suspensions  (2005)

Cortical microtubules participate in the deposition of patterned secondary walls in tracheary element differentiation. In this study, we established a system to induce the differentiation of tracheary elements using a transgenic Arabidopsis (Arabidopsis thaliana) cell suspension stably expressing a green fluorescent protein-tubulin fusion protein. Approximately 30% of the cells differentiated into tracheary elements 96 h after culture in auxin-free media containing 1 mum brassinolide. With this differentiation system, we have been able to time-sequentially elucidate microtubule arrangement during secondary wall thickening. The development of secondary walls could be followed in living cells by staining with fluorescein-conjugated wheat germ agglutinin, and the three-dimensional structures of the secondary walls could be simultaneously analyzed. A single microtubule bundle first appeared beneath the narrow secondary wall and then developed into two separate bundles locating along both sides of the developing secondary wall. Microtubule inhibitors affected secondary wall thickening, suggesting that the pair of microtubule bundles adjacent to the secondary wall played a crucial role in the regulation of secondary wall development.
Detection and target tracking with a quadrotor using fuzzy logic (2016)

In robotics and in many other applications, computer vision, object recognition and object tracking have been subject to a lot of active research with many different approaches and interesting results. In our project, we consider the automatic target-tracking problem in order to find an efficient and useful method for UAV. We use AR.Drone 2.0 as the air platform for tracking a target. In order to guarantee that the AR.Drone can recognize the target for correctly, QR code and ar_track_alvar are used as the target marker. The control of the drone is done using Robot Operating System (ROS). In this paper, we present the tracking-target control law based on a fuzzy logic controller. Input to the fuzzy logic controller is the information acquired from the cameras. Obtained information from vision system can be easily fitted fuzzy logic rules. The proposed algorithm is based on a small number of input parameters, what results in low requirements of computational power. The algorithm was checked during simulation studies. Simulation results prove the efficiency of the proposed intelligent control strategy.
<title>Carbon fiber composite photomask stage component</title> (1999)

The semiconductor industry utilizes complex patterning tools to achieve the patterning of fine features. These tools require stiff, lightweight, dimensionally stable components in order to reliably pattern photomasks and wafers. Traditionally, these tools have used metals, ceramics, and low expansion glasses. However, a new class of materials, high performance composites, have demonstrated promise for replacing these materials. This paper discusses the design, manufacturing, and test of a carbon fiber composite stage component of an electron beam lithography tool.
Exposure to IL-15 and IL-21 Enables Autoreactive CD8 T Cells To Respond to Weak Antigens and Cause Disease in a Mouse Model of Autoimmune Diabetes (2011)

Autoreactive CD8(+) T lymphocytes play a key role in the pathogenesis of several autoimmune diseases. It is not yet well understood how autoreactive CD8(+) T cells, which express TCRs with low reactivity toward self-Ags, gain the ability to respond to autoantigens to cause disease. Previously, we have shown that prior stimulation of CD8(+) T cells with synergistic combinations of cytokines produced by the innate immune response, such as IL-21 and IL-15, induces Ag-independent proliferation. Such "cytokine-primed" CD8 T cells displayed increased responsiveness to limiting quantities of the cognate Ag. In this paper, we report that prior stimulation with IL-15 and IL-21 also enables CD8(+) T cells to respond to weakly agonistic TCR ligands, resulting in proliferation, cytokine secretion, and cytolytic activity. Using a transgenic mouse model of autoimmune diabetes, we show that cytokine-primed autoreactive CD8(+) T cells induce disease following stimulation by weak TCR ligands, but their diabetogenic potential is dependent on continuous availability of IL-15 in vivo. These findings suggest that inflammatory cytokines could facilitate the triggering of autoreactive CD8(+) T cells by weak autoantigens, and this mechanism may have important implications for autoimmune diseases associated with microbial infections and chronic inflammation.
A Robust Method for Hands Gesture Recognition from Egocentric Depth Sensor (2018)

We present a method for robust and accurate hand pose recognition from egocentric depth cameras. Our method combines CNN based hand pose estimation and joint locations based hand gesture recognition. In pose estimation stage, we use a hand geometry prior network to estimate the hand pose. In gesture recognition stage, we defined a hand language which based on a set of pre-define basic propositions, obtained by applying four predicate types to the fingers and palm states. The hand language is used to convert the estimated joint location to hand gesture. Our experimental results indicate that the method enables robust and accurate gesture recognition in self-occlusion environment.