gebhart/patrepeval huggingface dataset:
Low Complexity, High Speed Decoder Architecture for Quasi-Cyclic LDPC Codes (2005)

This paper presents a low complexity, very high speed decoder architecture for quasi-cyclic low density parity check (QC-LDPC) codes, specifically Euclidian geometry (EG) based QC-LDPC codes. Algorithmic transformation and architectural level optimizations are employed to increase the clock speed. Enhanced partially parallel decoding architectures are proposed to linearly increase the overall throughput with the introduction of a small percentage of extra hardware. Based on the proposed architecture, a FPGA implementation of a (8176, 7154) EG-LDPC decoder can achieve a worst-case throughput of 169 Mbit/s.
Acute effects of dronedarone on both components of the cardiac delayed rectifier K+ current, HERG and KvLQT1/minK potassium channels (2003)

Dronedarone is a noniodinated benzofuran derivative that has been synthesized to overcome the limiting iodine-associated adverse effects of the potent antiarrhythmic drug amiodarone. In this study, the acute electrophysiological effects of dronedarone on repolarizing potassium channels were investigated to determine the class III antiarrhythmic action of this compound. HERG and KvLQT1/minK potassium channels conduct the delayed rectifier potassium current IK in human heart, being a primary target for class III antiarrhythmic therapy. HERG and KvLQT1/minK were expressed heterologously in Xenopus laevis oocytes, and the respective potassium currents were recorded using the two-microelectrode voltage-clamp technique. Dronedarone blocked HERG channels with an IC50 value of 9.2 microM and a maximum tail current reduction of 85.2%. HERG channels were blocked in the closed, open, and inactivated states. The half-maximal activation voltage was shifted by -6.1 mV, and HERG current block by dronedarone was voltage-dependent, but not use-dependent. Dronedarone exhibited a weaker block of KvLQT1/minK currents (33.2% at 100 microM drug concentration), without causing significant changes in the corresponding current-voltage relationships. In conclusion, these data demonstrate that dronedarone is an antagonist of cloned HERG potassium channels, with additional inhibitory effects on KvLQT1/minK currents at higher drug concentrations, providing a molecular mechanism for the class III antiarrhythmic action of the drug.
A Biomedical Implantable FES Battery-Powered Micro-Stimulator (2009)

The integrated circuit (IC) designs of an implantable functional electrical stimulation (FES) battery-powered micro-stimulator are presented in this paper. The battery is recharged by receiving power magnetically through a coil under supervision of a power management unit. To limit the heat generation on the stimulator when a large magnetic field is present, an on-chip rectifier is capable of limiting the induced voltage and reducing heat generation by providing a low impedance path. The same coil is also used for generating and receiving magnetic fields such that the distances among 16 different stimulator pairs can be estimated simultaneously. To facilitate different clinical applications, a bio-potential sensor is also included. The micro-stimulator can output mono-phasic stimulation current from an 8-bit exponential digital to analog converter (DAC) that has a range between ~2.5 ¿A and ~10 mA. The stimulator communicates with an external master control unit through a 400-MHz wireless link that can support a bit rate of 2.486 MB/s in high speed mode. The total number of stimulators that the communication system can support is 852.
Clinical pharmacokinetics of tumor necrosis factor antagonists. (2005)

Clinical pharmacokinetics of the 3 existing marketed tumor necrosis factor (TNF) antagonists, adalimumab (Abbott Laboratories), etanercept (Amgen, Inc.), and infliximab (Centocor, Inc.) are reviewed. The relevance and potential clinical implications of any differences in their pharmacokinetic properties are outlined. The major therapeutic goal when administering TNF antagonists is to eliminate the surplus of TNF from the circulation and from sites of inflammation. Within the causal chain of events after a drug is administered the exposure (or pharmacokinetics) precedes the effect (or pharmacodynamics). The differences in the observed concentration-time profiles and the exposure characteristics derived from them are induced either by differences of the inherent properties of the molecules (such as binding to various receptors, absorption and clearance mechanisms and rates, etc.), or by the differences in the dosage and administration regimens of the drugs (such as dose magnitude, administration frequency, route of administration, etc.). Review of the dose exposure-response cascade of the TNF antagonists shows that: (1) their pharmacokinetic properties should be interpreted in the context of the "therapeutic window" paradigm; and (2) exposure of tissues and fluids is a primary determinant of the drug action/adverse action. Therefore, efforts should be made to evaluate the pharmacokinetics of the TNF antagonists in such tissues/fluids of interest as the inflammation sites (e.g., synovium, gut mucosa, skin lesions) and sites of potential adverse effects (e.g., lungs).
Gradients of substrate-bound laminin orient axonal specification of neurons (2002)

Little is known about the influence of substrate-bound gradients on neuronal development, since it has been difficult to fabricate gradients over the distances typically required for biological studies (a few hundred micrometers). This article demonstrates a generally applicable technique for the fabrication of substrate-bound gradients of proteins with complex shapes, using laminar flows in microchannels. Gradients that range from pure laminin to pure BSA were formed in solution by using a network of microchannels, and these proteins were allowed to adsorb onto a homogeneous layer of poly-l-lysine. Rat hippocampal neurons were cultivated on these substrate-bound gradients. Analysis of optical images of these neurons showed that axon specification is oriented in the direction of increasing surface density of laminin. Linear gradients in laminin adsorbed from a gradient in solution having a slope of nabla [laminin] > about 0.06 microg (ml.microm)(-1) (defined by dividing the change of concentration of laminin in solution over the distance of the gradient) orient axon specification, whereas those with nabla [laminin] < about 0.06 microg (ml.microm)(-1) have no effect.
Heterocyclische Siebenring‐Verbindungen, XXV Synthese und thermische Umlagerung von substituierten 1‐Methyl‐4‐phenyl‐1‐benzothiepinium‐Salzen (1983)

Abstract Die 1‐Methyl‐4‐phenyl‐1‐benzothiepinium‐Salze 2a ‐ e wurden durch Alkylierung der entsprechend substituierten 1‐Benzothiepine 1a ‐ e mit Fluorsulfonsäure‐methylester dargestellt. Die Salze 2a ‐ e sind thermisch stabiler als die jeweiligen Verbindungen 1a ‐ e . Bei der Thermolyse entstehen aus 2a ‐ e die die entsprechenden α‐Naphthyl(methyl)thioether 3a ‐ e . Die Geschwindigkeitskonstanten dieser Reaktion wurden für je eine Temperatur bestimmt.
Software for the next-generation automobile (2003)

Automotive electronic systems are changing rapidly, requiring connectivity of all types. Ford's prototype software framework lets manufacturers rapidly tailor features and handle diverse communication modes. Ford Research and Advanced Engineering is working on a software architecture that provides the layers of abstraction necessary to realize this goal. The system, vehicle consumer services interface (VCSI), offers the ability to flexibly personalize and upgrade systems with the level of security required for mobile services, as well as a plug-and-play approach to device connectivity. It uses XML (eXtensible Markup Language) to communicate with portable devices and off-board systems, providing Ford the freedom to offer the highest degree of branding and personalization possible. Ford's proprietary XML-based interface, VUML (vehicle user-interface mark-up language) separates the MI from the core application, which lets designers use many HMI component types - from knobs, switches, and buttons to touch screen displays and conversational voice-activation systems. Thus, manufacturers can offer various features and functions in their products by choosing the HMI type that best aligns with their brand attributes and their customers' preferences. Using various input methods, consumers can easily control a particular function from more than one location. The driver, for example, can use voice commands to set the vehicle's temperature, while the front-seat passenger might use a button or touch screen for the same function. VCSI is based on Java, so designers can use a Java Virtual Machine (JVM) to abstract it from the platform and operating system (OS). We are currently using the QNX platform for embedded devices, but designers can implement VCSI on any platform that meets the specification and provides a JVM. With the CDC, foundation profile (one of the standard profiles for handheld devices that use Java) enables a VCSI-based solution to perform very well, providing all the desired functions and services. Ford has established a set of OS criteria that focuses on robustness and real-time execution specifications. One key element is that the OS must be able to start and stop device drivers and applications without having to reboot. This is especially important in a vehicle because consumers need devices and off-board connectivity at different and unpredictable times.
Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study. (1997)

After 1 year, moderate restriction of dietary fat intake attains meaningful and sustained LDL-C reductions in HC subjects and apoprotein B reductions in both HC and CHL subjects. More extreme restriction of fat intake offers little further advantage in HC or CHL subjects and potentially undesirable effects in HC subjects.
Seizure prediction by nonlinear EEG analysis (2003)

Attempting to increase insight into the spatio-temporal dynamics of the epileptogenic process to address one of the greatest challenges in epileptology. In the field of EEG analysis the search for the hidden information predictive of an impending seizure has a long history. The nonlinear EEG analysis techniques we have used in principle allow one to define a pre-ictal state and to characterize different temporal and spatial aspects of this state. The results obtained so far emphasize the high value of nonlinear EEG analysis techniques for the detection of a long-lasting pre-ictal state. Once given a sufficient sensitivity and specificity of seizure prediction techniques, more extensive clinical studies on a larger population of patients, either at home or in a clinical setting, can be envisaged.
Alternative Splicing of the Unique “PLUS” Domain of Chicken PG-M/Versican Is Developmentally Regulated (1997)

We investigated the occurrence of alternatively spliced forms (V0, V1, V2, and V3) of PG-M/versican, a large chondroitin sulfate proteoglycan in developing chicken retinas, using the reverse transcription-polymerase chain reaction. We characterized the PLUS domain, which is apparently unique to the chicken molecule and is regulated by alternative splicing. PG-M in chicken retinas consisted of four forms with (V0, V1, V2, and V3) and two forms without (V1 and V3) the PLUS domain (PG-M+ and PG-M-, respectively). The four forms of PG-M+ were found in all samples examined, but the occurrence of the two PG-M- forms was regulated developmentally. Genomic analysis has revealed that the PLUS and CS-alpha domains are encoded by a single exon, and this exon has an internal alternative 5'-splice donor site, allowing alternative spliced forms that do not include the 3'-end of the exon. Sequences corresponding to the chicken PLUS domain (plus) were not found in mouse and human and may have disappeared during evolution. Sequence similarity suggests that the PLUS domain corresponds to the keratan sulfate attachment domain of aggrecan and that it has a distinct function in the chicken eye.
Smart Aptamers Facilitate Multi-Probe Affinity Analysis of Proteins with Ultra-Wide Dynamic Range of Measured Concentrations (2007)

Protein concentration can vary over several orders of magnitude in many physiological, pathological, and biotechnological processes. Studies of these processes require affinity analysis of proteins with a wide dynamic range of accurately measured concentrations. The wide dynamic range can be achieved with multiple affinity probes that bind the target with significantly different equilibrium constants (Kd). Every probe in such a multi-probe affinity analysis is responsible for detection of the target in a range of concentrations around its Kd value. A multi-probe affinity analysis of proteins has not become practical so far due to the lack of generic affinity probes with a wide range of Kd and high selectivity. Kinetic capillary electrophoresis (KCE) has been recently proven to generate smart DNA aptamers with a wide range of predefined values of Kd and high selectivity. Here, we demonstrate, for the first time, that such aptamers can facilitate multi-probe affinity analysis of a protein with an ultra-wide dynamic range of measured concentrations. Our results showed that a three-aptamer analysis had a concentration dynamic range of more than 4 orders of magnitude. To the best of our knowledge, this is the widest dynamic range ever reported for affinity analyses of proteins. Advantageously, protein concentration in a multi-aptamers analysis can be determined using a simple calibration-free approach. This work proves that the wide range of predefined binding parameters of smart aptamers can bring new capabilities to quantitative affinity analyses. The same feature of smart aptamers makes them potentially indispensable molecular tools in studies of intracellular processes.
Synthesis and in Vitro Pharmacology of Substituted Quinoline-2,4-dicarboxylic Acids as Inhibitors of Vesicular Glutamate Transport (2002)

The vesicular glutamate transport (VGLUT) system selectively mediates the uptake of L-glutamate into synaptic vesicles. Uptake is linked to an H+-ATPase that provides coupling among ATP hydrolysis, an electrochemical proton gradient, and glutamate transport. Substituted quinoline-2,4-dicarboxylic acids (QDCs), prepared by condensation of dimethyl ketoglutaconate (DKG) with substituted anilines and subsequent hydrolysis, were investigated as potential VGLUT inhibitors in synaptic vesicles. A brief panel of substituted QDCs was previously reported (Carrigan et al. Bioorg. Med. Chem. Lett. 1999, 9, 2607-2612)(1) and showed that certain substituents led to more potent competitive inhibitors of VGLUT. Using these compounds as leads, an expanded series of QDC analogues were prepared either by condensation of DKG with novel anilines or via aryl-coupling (Suzuki or Heck) to dimethyl 6-bromoquinolinedicarboxylate. From the panel of almost 50 substituted QDCs tested as inhibitors of the VGLUT system, the 6-PhCH=CH-QDC (K(i) = 167 microM), 6-PhCH2CH2-QDC (K(i) = 143 microM), 6-(4'-phenylstyryl)-QDC (K(i) = 64 microM), and 6-biphenyl-4-yl-QDC (K(i) = 41 microM) were found to be the most potent blockers. A preliminary assessment of the key elements needed for binding to the VGLUT protein based on the structure-activity relationships for the panel of substituted QDCs is discussed herein. The substituted QDCs represent the first synthetically derived VGLUT inhibitors and are promising templates for the development of selective transporter inhibitors.
Census and evaluation of p53 target genes (2017)

The tumor suppressor p53 functions primarily as a transcription factor. Mutation of the TP53 gene alters its response pathway, and is central to the development of many cancers. The discovery of a large number of p53 target genes, which confer p53's tumor suppressor function, has led to increasingly complex models of p53 function. Recent meta-analysis approaches, however, are simplifying our understanding of how p53 functions as a transcription factor. In the survey presented here, a total set of 3661 direct p53 target genes is identified that comprise 3509 potential targets from 13 high-throughput studies, and 346 target genes from individual gene analyses. Comparison of the p53 target genes reported in individual studies with those identified in 13 high-throughput studies reveals limited consistency. Here, p53 target genes have been evaluated based on the meta-analysis data, and the results show that high-confidence p53 target genes are involved in multiple cellular responses, including cell cycle arrest, DNA repair, apoptosis, metabolism, autophagy, mRNA translation and feedback mechanisms. However, many p53 target genes are identified only in a small number of studies and have a higher likelihood of being false positives. While numerous mechanisms have been proposed for mediating gene regulation in response to p53, recent advances in our understanding of p53 function show that p53 itself is solely an activator of transcription, and gene downregulation by p53 is indirect and requires p21. Taking into account the function of p53 as an activator of transcription, recent results point to an unsophisticated means of regulation.
The complexity of lipoprotein (a) lowering by PCSK9 monoclonal antibodies (2017)

Since 2012, clinical trials dedicated to proprotein convertase subtilisin kexin type 9 (PCSK9) inhibition with monoclonal antibodies (mAbs) have unambiguously demonstrated robust reductions not only in low-density lipoprotein (LDL) cholesterol (LDL-C) but also in lipoprotein (a) [Lp(a)] levels. The scientific literature published prior to those studies did not provide any evidence for a link between PCSK9 and Lp(a) metabolism. More recent investigations, either in vitro or in vivo, have attempted to unravel the mechanism(s) by which PCSK9 mAbs reduce circulating Lp(a) levels, with some showing a specific implication of the LDL receptor (LDLR) in Lp(a) clearance whereas others found no significant role for the LDLR in that process. This elusive pathway appears clearly distinct from that of the widely prescribed statins that also enhance LDLR function but do not lower circulating Lp (a) levels in humans. So how does PCSK9 inhibition with mAbs reduce Lp(a)? This still remains to be established.
Concise Review: Adipose-Derived Stromal Vascular Fraction Cells and Platelet-Rich Plasma: Basic and Clinical Implications for Tissue Engineering Therapies in Regenerative Surgery (2012)

Cell-based therapy and regenerative medicine offer a paradigm shift in regard to various diseases causing loss of substance or volume and tissue or organ damage. Recently, many authors have focused their attention on mesenchymal stem cells for their capacity to differentiate into many cell lineages. The most widely studied types are bone marrow mesenchymal stem cells and adipose-derived stem cells (ADSCs), which display similar results. Based on the literature, we believe that the ADSCs offer advantages because of lower morbidity during the harvesting procedure. Additionally, platelet-rich plasma can be used in this field for its ability to stimulate tissue regeneration. The aims of this article are to describe ADSC preparation and isolation procedures, preparation of platelet-rich plasma, and the application of ADSCs in regenerative plastic surgery. We also discuss the mechanisms and future role of ADSCs in cell-based therapy and tissue engineering.
Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces (1980)

Using ellipsometry, anodized tantalum interference color, and Coomassie blue staining in conjunction with immunologic identification of proteins adsorbed at interfaces, we have previously found that fibrinogen is the main constituent deposited by plasma onto many man-made surfaces. However, the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically. In earlier publications, we have called this modification of the fibrinogen layer "conversion," to indicate a process of unknown nature. Conversion of adsorbed fibrinogen by the plasma was not accompanied by marked change in film thickness, so that we presumed that this fibrinogen was not covered but replaced by other protein. Conversion is now showen to be markedly delayed in plasma lacking high molecular weight kininogen, slightly delayed in plasma lacking factor XII, and normal in plasma that lack factor XI or prekallikrein. We conclude that intact plasma will quickly replace the fibrinogen it has deposited on glass-like surfaces by high molecular weight kininogen and, to a smaller extent, by factor XII. Platelets adhere preferentially to fibrinogen-coated surfaces; human platelets adhere to hydrophobic nonactivating surfaces, since on these, adsorbed firbinogen is not exchanged by the plasma. The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting, and platelets failing to find fibrinogen will not adhere.
Microbial conversion of sugars from plant biomass to lactic acid or ethanol (2008)

Concerns for our environment and unease with our dependence on foreign oil have renewed interest in converting plant biomass into fuels and 'green' chemicals. The volume of plant matter available makes lignocellulose conversion desirable, although no single isolated organism has been shown to depolymerize lignocellulose and efficiently metabolize the resulting sugars into a specific product. This work reviews selected chemicals and fuels that can be produced from microbial fermentation of plant-derived cell-wall sugars and directed engineering for improvement of microbial biocatalysts. Lactic acid and ethanol production are highlighted, with a focus on engineered Escherichia coli.
Unified Language Model Pre-training for Natural Language Understanding and Generation (2019)

This paper presents a new Unified pre-trained Language Model (UniLM) that can be fine-tuned for both natural language understanding and generation tasks. The model is pre-trained using three types of language modeling tasks: unidirectional, bidirectional, and sequence-to-sequence prediction. The unified modeling is achieved by employing a shared Transformer network and utilizing specific self-attention masks to control what context the prediction conditions on. UniLM compares favorably with BERT on the GLUE benchmark, and the SQuAD 2.0 and CoQA question answering tasks. Moreover, UniLM achieves new state-of-the-art results on five natural language generation datasets, including improving the CNN/DailyMail abstractive summarization ROUGE-L to 40.51 (2.04 absolute improvement), the Gigaword abstractive summarization ROUGE-L to 35.75 (0.86 absolute improvement), the CoQA generative question answering F1 score to 82.5 (37.1 absolute improvement), the SQuAD question generation BLEU-4 to 22.12 (3.75 absolute improvement), and the DSTC7 document-grounded dialog response generation NIST-4 to 2.67 (human performance is 2.65). The code and pre-trained models are available at https://github.com/microsoft/unilm.
Abundant empty class II MHC molecules on the surface of immature dendritic cells (1999)

A monoclonal antibody specific for the empty conformation of class II MHC molecules revealed the presence of abundant empty molecules on the surface of spleen- and bone marrow-derived dendritic cells (DC) among various types of antigen-presenting cells. The empty class II MHC molecules are developmentally regulated and expressed predominantly on immature DC. They can capture peptide antigens directly from the extracellular medium and present bound peptides to antigen-specific T lymphocytes. The ability of the empty cell-surface class II MHC proteins to bind peptides and present them to T cells without intracellular processing can serve to extend the spectrum of antigens able to be presented by DC, consistent with their role as sentinels in the immune system.