gebhart/patrepeval huggingface dataset:
Slow Onset Inhibition of Bacterial β-Ketoacyl-acyl Carrier Protein Synthases by Thiolactomycin (2009)

Thiolactomycin (TLM), a natural product thiolactone antibiotic produced by species of Nocardia and Streptomyces, is an inhibitor of the beta-ketoacyl-acyl carrier protein synthase (KAS) enzymes in the bacterial fatty acid synthase pathway. Using enzyme kinetics and direct binding studies, TLM has been shown to bind preferentially to the acyl-enzyme intermediates of the KASI and KASII enzymes from Mycobacterium tuberculosis and Escherichia coli. These studies, which utilized acyl-enzyme mimics in which the active site cysteine was replaced by a glutamine, also revealed that TLM is a slow onset inhibitor of the KASI enzymes KasA and ecFabB but not of the KASII enzymes KasB and ecFabF. The differential affinity of TLM for the acyl-KAS enzymes is proposed to result from structural change involving the movement of helices alpha5 and alpha6 that prepare the enzyme to bind malonyl-AcpM or TLM and that is initiated by formation of hydrogen bonds between the acyl-enzyme thioester and the oxyanion hole. The finding that TLM is a slow onset inhibitor of ecFabB supports the proposal that the long residence time of TLM on the ecFabB homologues in Serratia marcescens and Klebsiella pneumonia is an important factor for the in vivo antibacterial activity of TLM against these two organisms despite the fact that the in vitro MIC values are only 100-200 microg/ml. The mechanistic data on the interaction of TLM with KasA will provide an important foundation for the rational development of high affinity KasA inhibitors based on the thiolactone skeleton.
Vaccination of sows with a dendritic cell-targeted porcine epidemic diarrhea virus S1 protein-based candidate vaccine reduced viral shedding but exacerbated gross pathological lesions in suckling neonatal piglets (2018)

Porcine epidemic diarrhea virus (PEDV) poses a serious threat to swine worldwide as evidenced by its recent introduction into the USA and the devastating economic impact it caused to the USA swine industry. Commercial vaccines against PEDV are available but their efficacies are inadequate. Therefore, vaccines with improved efficacy are needed to effectively control PEDV infections. We previously determined the immunogenicity of a novel dendritic cell (DC)-targeted PEDV S1 protein-based subunit vaccine in weaned piglets in which the PEDV antigen was targeted to DCs through a porcine Langerin-specific antibody. In this study, we evaluated the protective efficacy of this DC-targeting vaccine by immunizing sows at 5 and 2 weeks prior to farrowing and by challenging the 5-day-old piglets with PEDV. The results showed that immunization of sow with DC-targeted PEDV vaccine did not eliminate faecal virus shedding in piglets but significantly reduced faecal viral RNA levels in the early days after virus challenge. The vaccine also reduced the amount of PEDV antigen in intestinal tissues presented with intestinal villi regrowth. However, the DC-targeted vaccine neither mitigated PEDV clinical signs nor affected viral RNA loads in intestinal tissues of piglets. In the vaccinated sow, DC-targeted PEDV vaccine enhanced T helper 1-like cluster of differentiation (CD)4 T cell responses and induced IgG but not IgA-specific immune responses. The suckling piglets in the DC-targeted vaccine group showed increased gross pathological lesions in the small intestine. Results in this study provide insights into the effects of sow cellular immune responses to PEDV infection in suckling piglets.
A simulation about the influence of the gate-source-drain distance on the AlGaN/GaN HEMT performance at Ka-band (2012)

To improve the frequency and the output power, we present the results on the effect of distance between source-gate-drain in AlGaN/GaN high electron mobility transistors (HEMTs) by silvaco emulator. First, we adopt centrosymmetric gate structure, it means the L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">gs</sub> (source-gate spacing) is equal to the L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">gd</sub> (gate-drain spacing), and the L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sd</sub> (source-drain spacing)changes from 4μm to 2.4 um. It presents that the drain current, transconductance, the gain at 35GHz, f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> (current gain cutoff frequency)and f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> (maximum frequency of oscillation)get improved with the decrease of L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sd</sub> . However, when the distance comes to a certain extent, the fringe scatter from ohmic contact of source and drain would weaken electron mobility in channel layer, and it is hard to improve in technology fabrication. In addition, changing the L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sg</sub> and L <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">dg</sub> simultaneously demonstrates the influence of the different gate locations. Finally, we get the range of source-gate-drain distance for Ka-band AlGaN/GaN HEMT by the simulation results.
Dehydroluciferyl‐AMP is the main intermediate in the luciferin dependent synthesis of Ap<sub>4</sub>A catalyzed by firefly luciferase (1998)

It was previously assumed that E x LH2-AMP was the intermediate complex in the synthesis of Ap4A catalyzed by firefly luciferase (EC 1.13.12.7), when luciferin (LH2) was used as cofactor. However, here we show that LH2 is partly transformed, shortly after the onset of the luciferase reaction, to dehydroluciferin (L) with formation of an E x L-AMP complex which is the main intermediate for the synthesis of Ap4A. Formation of three more derivatives of LH2 were also observed, related to the production of light by the enzyme. CoA, a known stimulator of light production, inhibits the synthesis of Ap4A by reacting with the E x L-AMP complex and yielding L-CoA.
Discovery of a Potent Parenterally Administered Factor XIa Inhibitor with Hydroxyquinolin-2(1<i>H</i>)-one as the P2′ Moiety (2015)

Structure-activity relationship optimization of phenylalanine P1' and P2' regions with a phenylimidazole core resulted in a series of potent FXIa inhibitors. Introducing 4-hydroxyquinolin-2-one as the P2' group enhanced FXIa affinity and metabolic stability. Incorporation of an N-methyl piperazine amide group to replace the phenylalanine improved both FXIa potency and aqueous solubility. Combination of the optimization led to the discovery of FXIa inhibitor 13 with a FXIa K i of 0.04 nM and an aPTT EC2x of 1.0 μM. Dose-dependent efficacy (EC50 of 0.53 μM) was achieved in the rabbit ECAT model with minimal bleeding time prolongation.
The molecular makeup and function of regulatory and effector synapses (2007)

Physical interactions between T cells and antigen-presenting cells (APCs) form the basis of any specific immune response. Upon cognate contacts, a multimolecular assembly of receptors and adhesion molecules on both cells is created, termed the immunological synapse (IS). Very diverse structures of ISs have been described, yet the functional importance for T-cell differentiation is largely unclear. Here we discuss the principal structure and function of ISs. We then focus on two characteristic T-cell-APC pairs, namely T cells contacting dendritic cells (DCs) or naive B cells, for which extremely different patterns of the IS have been observed as well as fundamentally different effects on the function of the activated T cells. We provide a model on how differences in signaling and the involvement of adhesion molecules might lead to diverse interaction kinetics and, eventually, diverse T-cell differentiation. We hypothesize that the preferred activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and of the negative regulator for T-cell activation, cytotoxic T-lymphocyte antigen-4 (CTLA-4), through contact with naive B cells, lead to prolonged cell-cell contacts and the generation of T cells with regulatory capacity. In contrast, DCs might have evolved mechanisms to avoid LFA-1 overactivation and CTLA-4 triggering, thereby promoting more dynamic contacts that lead to the preferential generation of effector cells.
African—American Art: Redefining the Canon (2010)

(2010). African—American Art: Redefining the Canon. Critical Interventions: Vol. 4, Transformations, pp. 16-26.
Nearest-neighbor image model (2012)

We propose a novel, adaptive model for image representation. The model places image pixels on the nodes of a two-dimensional nearest-neighbor graph. Edge weights for the graph depend on the image of interest, and can be determined by solving a corresponding least-squares problem. The proposed model is shown to provide an efficient image representation well-suited for image compression.
Measurement of output intensities of multiple-mode diagnostic ultrasound systems using thermoacoustic sensors (2006)

Simple and low-cost thermoacoustic sensors are calibrated to enable quantitative ultrasound time-averaged intensity measurements. The sensors are applied to exposure measurements on a diagnostic ultrasound system. Comparison of the results with the intensity values derived from additional hydrophone measurements shows very good agreement. The sensor technique can be used efficiently to identify the parameter settings of a diagnostic machine which lead to maximum acoustic output. Therefore, it can reduce the expenses for regulatory testing and may improve the results and the reliability of output parameter declarations.
Direct Immobilization and Patterning of Hyaluronic Acid on Hydrophilic Substrates (2005)

In this study, we describe two methods of patterning HA on various substrates including glass, silicon dioxides, poly (hydroxyethyl methacrylate) [poly (HEMA)], polystyrene cell culture dishes, and biodegradable polylactic glycolic acid (PLGA), without the use of chemical modification or with slight modification with NaOH or oxygen plasma treatment. Such versatile use of soft lithographic methods would be potentially useful for many biomedical applications.
The Effects of Information Systems Quality on Nurses’ Acceptance of the Electronic Learning System (2012)

User-interface design quality is the most key antecedent that can make significant impacts on nurses' PU and PE, and more efforts should be made to develop a friendlier user interface via designing useful and enjoyable features to induce nurses to use the e-learning system. Moreover, system quality can make the greatest impact on nurses' PEOU; thus, medical institutions should effectively enhance system quality to deliver benefits and pleasure to boost nurses' usage intention of the e-learning system via reducing the complexity.
Tetrahydropterin-Dependent Amino Acid Hydroxylases (1999)

Phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase constitute a small family of monooxygenases that utilize tetrahydropterins as substrates. When from eukaryotic sources, these enzymes are composed of a homologous catalytic domain to which are attached discrete N-terminal regulatory domains and short C-terminal tetramerization domains, whereas the bacterial enzymes lack the N-terminal and C-terminal domains. Each enzyme contains a single ferrous iron atom bound to two histidines and a glutamate. Recent mechanistic studies have begun to provide insights into the mechanisms of oxygen activation and hydroxylation. Although the hydroxylating intermediate in these enzymes has not been identified, the iron is likely to be involved. Reversible phosphorylation of serine residues in the regulatory domains affects the activities of all three enzymes. In addition, phenylalanine hydroxylase is allosterically regulated by its substrates, phenylalanine and tetrahydrobiopterin.
ROS-Production–Mediated Activation of AP-1 but Not NFκB Inhibits Glutamate-Induced HT4 Neuronal Cell Death (2006)

Aside from their deleterious effect, reactive oxygen species (ROS) can function as small messenger molecules during physiologic processes. ROS have been shown to activate the transcription nuclear factor kappa B (NFkappaB) and activator protein 1 (AP-1). Exposure of HT4 neuronal cells to 10 mM glutamate results in cell death after 12 h. Here we show that glutamate treatment leads to an increase in ROS production and activation of AP-1, but not NFkappaB. 12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C and an inducer of NFkappaB and AP-1, protected the cells. This protective effect was preceded by increased production of ROS compared with glutamate alone, which was accompanied by a synergistic increase in AP-1, but not NFkappaB activity. We used all-trans-retinoic acid (ATRA), overexpression of retinoic acid receptor alpha (RARalpha) and a decoy oligonucleotide inclusion assay to suppress AP-1 activity. NFkappaB was inhibited by using a super suppressor (IkappaBalphaDeltaN-transfected cells). Inhibition of AP-1, but not NFkappaB resulted in increased cellular vulnerability to glutamate. Inhibition of AP-1 activity was coincident with a decrease in ROS production. Thus, although ROS are significant to the cell-death effect induced by glutamate, they also activate protective pathways mediated by increasing AP-1 activity, and not that of NFkappaB.
Clinical characteristics and risk factors analysis of lung metastasis from benign giant cell tumor of bone (2017)

Pulmonary metastasis of benign giant cell tumor of bone is very rare, and its biological behavior is difficult to predict. In the present study, we analyzed the clinical characteristics of and related risk factors for pulmonary metastasis of this tumor. Forty-six patients with lung metastasis were analyzed. In total, 60.9% of the primary tumors were located around the knee joint. The Campanacci stage of all tumors was stage 3. Surgery of the primary tumor included curettage in 37 patients, resection in 8, and amputation in 1. Local recurrence after the primary surgery occurred in 34 patients. The recurrence rate, Campanacci stage, and surgical method were significant risk factors for lung metastasis. The median postoperative metastasis time in the lower limbs, upper limbs, and axial skeleton was 20.1, 7.9, and 1.4 months, respectively (p=0.010). The median metastasis time in patients with and without recurrence was 13.7 and 43.2 months, respectively (p=0.018). Eighteen patients had unilateral metastasis and 28 had bilateral metastasis. Most lesions (n=38) were located in the peripheral lung. Nineteen patients received treatment, and 12 of them underwent tumor resection. The 5-year overall survival rate was 94.4%. This study showed that local recurrence, a high Campanacci stage, and curettage were possible high-risk factors for pulmonary metastasis. The primary lesion site and local recurrence may be related to the metastasis time. The survival rate of patients with pulmonary metastasis was high.
High-Density Amplicon Sequencing Identifies Community Spread and Ongoing Evolution of SARS-CoV-2 in the Southern United States (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving. Prior studies focused on high-case-density locations, such as the northern and western metropolitan areas of the United States. This study demonstrates continued SARS-CoV-2 evolution in a suburban southern region of the United States by high-density amplicon sequencing of symptomatic cases. 57% of strains carry the spike D614G variant, which is associated with higher genome copy numbers, and its prevalence expands with time. Four strains carry a deletion in a predicted stem loop of the 3' UTR. The data are consistent with community spread within local populations and the larger continental United States. The data instill confidence in current testing sensitivity and validate "testing by sequencing" as an option to uncover cases, particularly nonstandard coronavirus disease 2019 (COVID-19) clinical presentations. This study contributes to the understanding of COVID-19 through an extensive set of genomes from a non-urban setting and informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the United States.
Measurement of Activity (1993)

Activity is a phenomenon of concern to nursing. Although a wide variety of instruments have been used to measure activity, researchers have confronted barriers to its measurement in reliable, valid, and practical ways. Technological advances have stimulated theoretical and empirical developments in the study of activity by improving the physical instrumentation. This article presents an overview of methods used to measure human activity, with an emphasis on technological advances and the methods relevant to nursing. Self-report, behavioral observation, and mechanical and electronic activity measures are reviewed and critiqued.
A multifunctional human Argonaute2-specific monoclonal antibody (2008)

Small regulatory RNAs including small interfering RNAs (siRNAs), microRNAs (miRNAs), or Piwi interacting RNAs (piRNAs) guide regulation of gene expression in many different organisms. The Argonaute (Ago) protein family constitutes the cellular binding partners of such small RNAs and regulates gene expression on the levels of transcription, mRNA stability, or translation. Due to the lack of highly specific and potent monoclonal antibodies directed against the different Ago proteins, biochemical analyses such as Ago complex purification and characterization rely on overexpression of tagged Ago proteins. Here, we report the generation and functional characterization of a highly specific monoclonal anti-Ago2 antibody termed anti-Ago2(11A9). We show that anti-Ago2(11A9) is specific for human Ago2 and detects Ago2 in Western blots as well as in immunoprecipitation experiments. We further demonstrate that Ago2 can be efficiently eluted from our antibody by a competing peptide. Finally, we show that anti-Ago2(11A9) recognizes Ago2 in immunofluorescence experiments, and we find that Ago2 not only localizes to cytoplasmic processing bodies (P-bodies) and the diffuse cytoplasm but also to the nucleus. With the anti-Ago2(11A9) antibody we have generated a potent tool that is useful for many biochemical or cell biological applications.
Identification of a peptide fragment of DSCR1 that competitively inhibits calcineurin activity<i>in vitro</i>and<i>in vivo</i> (2005)

Calcineurin phosphatase activity regulates the nuclear localization of the nuclear factor of activated T cells (NFAT) family of transcription factors during immune challenge. Calcineurin inhibitors, such as the cyclosporin A-cyclophilin A and FK506-FKBP12 complexes, regulate this enzymatic activity noncompetitively by binding at a site distinct from the enzyme active site. A family of endogenous protein inhibitors of calcineurin was recently identified and shown to block calcineurin-mediated NFAT nuclear localization and transcriptional activation. One such inhibitor, Down Syndrome Critical Region 1 (DSCR1), functions in T cell activation, cardiac hypertrophy, and angiogenesis. We have identified a small region of DSCR1 that is a potent inhibitor of calcineurin activity in vitro and in vivo.
A Review of Current and Future Management of Geographic Atrophy (2017)

Age-related macular degeneration (AMD) is a multifactorial disease and a leading cause of vision impairment in elderly people in Western society. Geographic atrophy (GA), the late stage of dry AMD, is typically defined as a round or oval area of atrophy of 175 µm or more. In GA patients, visual acuity (VA) can still be good if the macula is spared, but decreased if GA extends through the fovea causing a great impairment of quality of life. Because of a poor correlation between VA and GA lesions or progression, a multimodal imaging approach is necessary to better follow up GA patients. In the last years, the introduction in clinical practice of new non-invasive tools such as fundus autofluorescence, structural optical coherence tomography (OCT) and OCT angiography helped the ophthalmologists to better understand the natural course of GA patients. However, several pathways concerning the pathogenesis of the disease are not completely clarified yet and should be investigated further. Although no approved therapy exists for GA, healthy lifestyle and nutritional intervention with some specific supplementations (e.g., vitamins C and E, beta-carotene, high dietary folate) may help to prevent the onset and to delay the progression of the disease. At the same time, several drugs are under evaluation in clinical trials with interesting results. These drugs try to stop several pathways implicated in the pathogenesis of GA, but probably only a few of these will prove truly effective, confirming the preliminary results, and will be available in clinical practice.
A Feedback A/F Control System for Low Emission Vehicles (1993)

<div class="htmlview paragraph">Recent Federal and California legislation have mandated major improvements in emission control. Tailpipe HC emission must be decreased an order of magnitude for the California Ultra Low Emission Vehicle (ULEV) standard. Present feedback A/F<span class="xref">*</span> control systems employ a Heated Exhaust Gas Oxygen sensor (HEGO sensor) upstream of the catalyst to perform A/F feedback control. Limitations on the ultimate accuracy of these switching sensors are well known. To overcome these limitations a linear Universal Exhaust Gas Oxygen sensor (UEGO sensor) placed downstream from the minicatalyst is employed to attain improved A/F control and therefore, higher three-way catalyst (TWC) conversion efficiency. This configuration was granted a patent in 1992 (<span class="xref">1</span><span class="xref">**</span>).</div> <div class="htmlview paragraph">This study compares performance differences between the two feedback control systems on a Ford Mustang. In initial studies both the UEGO and HEGO sensors were compared at the midposition location downstream of a minicatalyst. Although several HEGO calibrations were used, the UEGO sensor with Proportional-Integral (PI) control provided lower tailpipe emissions. Control loop frequency loss was minimal and the A/F control point stabilized by the filtering action of the minicatalyst.</div> <div class="htmlview paragraph">Control loop behavior was tested with aged minicatalysts and UEGO sensors to determine if a practical increase in the loop gain could be attained to compensate for catalyst aging.</div> <div class="htmlview paragraph">In conclusion, the midposition UEGO sensor feedback control, with further developement, appears to be a promising combination for future emission reduction.</div>
Finding someone in my social directory whom i do not fully remember or barely know (2012)

REACH is an intelligent, people-finding system that helps users to find someone in their social directory, especially those whom they do not fully remember or barely know. It analyzes a user's communication and social networking data to automatically extract all the contacts and derive multiple facets to characterize each contact in relation to the user. It then employs a personalized, faceted search to retrieve and present a ranked list of matched contacts based on their properties. A preliminary evaluation shows the effectiveness of our approach.