gebhart/patrepeval huggingface dataset:
Tissue distribution of adenosine receptor mRNAs in the rat (1996)

1. A degree of ambiguity and uncertainty exists concerning the distribution of mRNAs encoding the four cloned adenosine receptors. In order to consolidate and extent current understanding in this area, the expression of the adenosine receptors has been examined in the rat by use of in situ hybridisation and the reverse transcription-polymerase chain reaction (RT-PCR). 2. In accordance with earlier studies, in situ hybridisation revealed that the adenosine A1 receptor was widely expressed in the brain, whereas A2A receptor mRNA was restricted to the striatum, nucleus accumbens and olfactory tubercle. In addition, A1 receptor mRNA was detected in large striatal cholinergic interneurones, 26% of these neurones were also found to express the A2A receptor gene. Central levels of mRNAs encoding adenosine A2B and A3 receptors were, however, below the detection limits of in situ hybridisation. 3. The more sensitive technique of RT-PCR was then employed to investigate the distribution of adenosine receptor mRNAs in the central nervous system (CNS) and a wide range of peripheral tissues. As a result, many novel sites of adenosine receptor gene expression were identified. A1 receptor expression has now been found in the heart, aorta, liver, kidney, eye and bladder. These observations are largely consistent with previous functional data. A2A receptor mRNA was detected in all brain regions tested, demonstrating that expression of this receptor is not restricted to the basal ganglia. In the periphery A2A receptor mRNA was also found to be more widely distributed than generally recognised. The ubiquitous distribution of the A2B receptor is shown for the first time, A2B mRNA was detected at various levels in all rat tissues studied. Expression of the gene encoding the adenosine A3 receptor was also found to be widespread in the rat, message detected throughout the CNS and in many peripheral tissues. This pattern of expression is similar to that observed in man and sheep, which had previously been perceived to possess distinct patterns of A3 receptor gene expression in comparison to the rat. 4. In summary, this work has comprehensively studied the expression of all the cloned adenosine receptors in the rat, and in so doing, resolves some of the uncertainty over where these receptors might act to control physiological processes mediated by adenosine.
The Soluble and Membrane-bound Transhydrogenases UdhA and PntAB Have Divergent Functions in NADPH Metabolism of Escherichia coli (2004)

Pentose phosphate pathway and isocitrate dehydrogenase are generally considered to be the major sources of the anabolic reductant NADPH. As one of very few microbes, Escherichia coli contains two transhydrogenase isoforms with unknown physiological function that could potentially transfer electrons directly from NADH to NADP+ and vice versa. Using defined mutants and metabolic flux analysis, we identified the proton-translocating transhydrogenase PntAB as a major source of NADPH in E. coli. During standard aerobic batch growth on glucose, 35-45% of the NADPH that is required for biosynthesis was produced via PntAB, whereas pentose phosphate pathway and isocitrate dehydrogenase contributed 35-45% and 20-25%, respectively. The energy-independent transhydrogenase UdhA, in contrast, was essential for growth under metabolic conditions with excess NADPH formation, i.e. growth on acetate or in a phosphoglucose isomerase mutant that catabolized glucose through the pentose phosphate pathway. Thus, both isoforms have divergent physiological functions: energy-dependent reduction of NADP+ with NADH by PntAB and reoxidation of NADPH by UdhA. Expression appeared to be modulated by the redox state of cellular metabolism, because genetic and environmental manipulations that increased or decreased NADPH formation down-regulated pntA or udhA transcription, respectively. The two transhydrogenase isoforms provide E. coli primary metabolism with an extraordinary flexibility to cope with varying catabolic and anabolic demands, which raises two general questions: why do only a few bacteria contain both isoforms, and how do other organisms manage NADPH metabolism?
The physics of photodynamic therapy (1986)

This review covers the following topics: outstanding problems in photodynamic therapy (PDT); light sources for PDT; light delivery systems for PDT; light dosimetry; haematoporphyrin derivative quantification in vivo.
v-Src induces constitutive macropinocytosis in rat fibroblasts (1996)

The role of v-Src as regulator of fluid-phase pinocytosis was investigated in Rat-1 cells expressing a stable (Rat-1/BB16) or a thermosensitive (Rat-1/tsLA29) v-Src protein. In the second cell line, this protein is inactive when cells are cultured at 40 degrees C but recovers its tyrosine kinase activity upon transfer to 34 degrees C, resulting into a transformed phenotype. The rate of fluid-phase pinocytosis of the tracer horseradish peroxidase was 2-fold higher in v-Src-transformed fibroblasts (Rat-1/BB16, Rat-1/tsLA29 cultured at 34 degrees C) as compared to non-transformed cells (Rat-1, Rat-1/tsLA29 kept at 40 degrees C). In contrast, receptor-mediated endocytosis of transferrin was poorly affected, suggesting that structures distinct from clathrin-coated pits are involved in pinocytosis stimulation. By light and electron microscopy, transformed cells frequently contained large peroxidase-labeled pinocytic vesicles located near to membrane ruffles, demonstrating that stimulation of pinocytosis corresponds to induction of constitutive macropinocytosis. Stimulation of pinocytosis occurred more than 8 hours after transfer to the permissive temperature, whereas transfer to the non-permissive temperature partially reversed the stimulation within 2 hours. Protein synthesis inhibition for 6 hours abrogated pinocytosis stimulation in transformed cells, indicating that constitutive macropinocytosis induced by v-Src depends on continuous synthesis of a short-lived regulatory machinery.
Universal Quantum Computation with Continuous-Variable Cluster States (2006)

We describe a generalization of the cluster-state model of quantum computation to continuous-variable systems, along with a proposal for an optical implementation using squeezed-light sources, linear optics, and homodyne detection. For universal quantum computation, a nonlinear element is required. This can be satisfied by adding to the toolbox any single-mode non-Gaussian measurement, while the initial cluster state itself remains Gaussian. Homodyne detection alone suffices to perform an arbitrary multimode Gaussian transformation via the cluster state. We also propose an experiment to demonstrate cluster-based error reduction when implementing Gaussian operations.
STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. (2010)

STA-9090 is a second-generation Hsp90 inhibitor in clinical development by Synta Pharmaceuticals for the intravenous treatment of hematological and solid malignancies. It is a resorcinol-containing triazole compound, with a novel chemical structure that is unrelated to the geldanamycin class of Hsp90 inhibitors. STA-9090 binds to the ATP-binding domain at the N-terminus of Hsp90 and acts as a potent Hsp90 inhibitor by inducing degradation of multiple oncogenic Hsp90 client proteins including HER2/neu, mutated EGFR, Akt, c-Kit, IGF-1R, PDGFRα, Jak1, Jak2, STAT3, STAT5, HIF-1α, CDC2, c-Met, and Wilms' tumor 1. STA-9090, at low nanomolar concentrations, potently arrested cell proliferation and induced apoptosis in a wide variety of human cancer cell lines, including many receptor tyrosine kinase inhibitor- and tanespimycin-resistant cell lines. Moreover, administration of STA-9090 led to significant tumor shrinkage in several tumor xenograft models in mice and appeared to be less toxic. Furthermore STA-9090 demonstrated better tumor penetration compared with tanespimycin. In initial phase I clinical trials, STA-9090 was well tolerated and has demonstrated activity. The further development of this agent, and the other Hsp90 inhibitors, may be dependent on the tumor type and the primary oncogenic driving forces.
The Role of Anti-non-Gal Antibodies in the Development of Acute Humoral Xenograft Rejection of hDAF Transgenic Porcine Kidneys in Baboons Receiving Anti-Gal Antibody Neutralization Therapy (2006)

In a pig-to-baboon kidney transplant model, both preformed and induced anti-non-Gal antibodies are strongly associated with the pathogenesis of AHXR when anti-Gal antibodies are neutralized.
Synthesis of .alpha.-methylene-.gamma.-butyrolactones: a structure-activity relationship study of their allergenic power (1980)

Thirty-five alpha-methylene-gamma-butyrolactones have been prepared and their allergenic properties tested on the skin of guinea pigs experimentally sensitized to (a) alantolactone (1), (b) isoalantolactone (2), and (c) alpha-methylene-gamma-butyrolactone (3). The two first groups of animals cross-react to lactones containing 9 to 18 carbon atoms but not to smaller alpha-methylene-gamma-butyrolactones. Conversely, animals sensitized to alpha-methylene-gamma-butyrolactone react only with alpha-methylene-gamma-butyrolactones containing 6 and 7 carbon atoms. These results are discussed in relation with the allergic contact dermatitis mechanism.
Asterriquinones Produced by Aspergillus candidus Inhibit Binding of the Grb-2 Adapter to Phosphorylated EGF Receptor Tyrosine Kinase. (1999)

Five new asterriquinone analogs (2-4, 6, 7), together with previously identified neoasterriquinone (1) and isoasterriquinone (5), were isolated from a fermentation broth of the fungus Aspergillus candidus and purified by HSCCC (high speed counter current chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR and MS/MS techniques. All seven showed inhibitory activity against the binding of a recombinant protein containing the SH2 protein domain of Grb-2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase. Some of these asterriquinones exhibited specific inhibition of Grb-2 binding compared to Grb-7 and PLC-gamma.
Nano-Watt silicon-on-sapphire ADC using 2C-1C capacitor chain (2006)

An analogue-to-digital converter (ADC) in a 0.5 µm silicon-on-sapphire CMOS technology is reported. This innovative ADC uses a 2C-1C capacitor chain and a switched capacitor comparator. The ADC is capable of sampling at 409 kS/s, consuming 900 nW at 1.1 V power supply and 1.35 µW at 1.5 V. It uses an active area of 300×700 µm2 and 640×1070 µm2 with pads.
Structure-Based Design of HIV Protease Inhibitors: 4-Hydroxycoumarins and 4-Hydroxy-2-pyrones as Non-peptidic Inhibitors (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure-Based Design of HIV Protease Inhibitors: 4-Hydroxycoumarins and 4-Hydroxy-2-pyrones as Non-peptidic InhibitorsSuvit Thaisrivongs, Paul K. Tomich, Keith D. Watenpaugh, Kong-Teck Chong, W. Jeffrey Howe, Chih-Ping Yang, Joseph W. Strohbach, Steve R. Turner, James P. McGrath, and Cite this: J. Med. Chem. 1994, 37, 20, 3200–3204Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/jm00046a002https://doi.org/10.1021/jm00046a002research-articleACS PublicationsRequest reuse permissionsArticle Views639Altmetric-Citations135LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis (2010)

Apremilast is an orally available PDE4 inhibitor that reduces TNFalpha production from human synovial cells and significantly suppresses experimental arthritis. Apremilast appears to be a potential new agent for the treatment of rheumatoid arthritis.
Neointimal Thickening After Severe Coronary Artery Injury Is Limited by Short-term Administration of a Factor Xa Inhibitor (1996)

The specific factor Xa inhibitor rTAP, when given in fully anticoagulant doses for a short duration after coronary artery injury in the porcine model, resulted in a long-term decrease in neointimal thickness. These results implicate thrombin generation in neointimal formation and suggest that administration of a potent antithrombotic for several days immediately after the procedure may influence the long-term outcome of the coronary injury with a decrease in neointimal formation.
Compress Compound Images in H.264/MPGE-4 AVC by Exploiting Spatial Correlation (2009)

Compound images are a combination of text, graphics and natural image. They present strong anisotropic features, especially on the text and graphics parts. These anisotropic features often render conventional compression inefficient. Thus, this paper proposes a novel coding scheme from the H.264 intraframe coding. In the scheme, two new intramodes are developed to better exploit spatial correlation in compound images. The first is the residual scalar quantization (RSQ) mode, where intrapredicted residues are directly quantized and coded without transform. The second is the base colors and index map (BCIM) mode that can be viewed as an adaptive color quantization. In this mode, an image block is represented by several representative colors, referred to as base colors, and an index map to compress. Every block selects its coding mode from two new modes and the previous intramodes in H.264 by rate-distortion optimization (RDO). Experimental results show that the proposed scheme improves the coding efficiency even more than 10 dB at most bit rates for compound images and keeps a comparable efficient performance to H.264 for natural images.
Isotope-Ratio-Monitoring Liquid Chromatography Mass Spectrometry (IRM-LCMS): First Results from a Moving Wire Interface System (1996)

Abstract A Liquid Chromatography-Combustion (LC-C) Interface, based on a moving wire technique, has been built and tested. The LC effluent is deposited onto a transport wire, which carries the sample through solvent evaporation and combustion ovens. CO(2) from the combustion step is analysed in an isotope ratio mass spectrometer. Performance of the interface was tested by loop injections of sucrose and glucose into a liquid flow of methanol/water (80/20). Accuracy and precision of δ(13)C(PDB) < 1‰ was achieved for sample concentrations > 500 ng/ul (5μl loop), sufficient for studies at natural isotope ratios. In case of (13)C tracer applications the detection limit was determined to be about 20 pg carbon tracer (on wire).
Clinical toxicity of cryopreserved circulating progenitor cells infusion. (1999)

In our experience the infusion of cryopreserved peripheral blood progenitors caused minor to moderate toxicity in most cases and, when present, side effects were observed only during infusion. The amount of DMSO present in the graft is related to the grade of toxicity.
Nitrogen‐Doped Ordered Mesoporous Graphitic Arrays with High Electrocatalytic Activity for Oxygen Reduction (2010)

These materials are no dopes: Nitrogen-doped ordered mesoporous graphitic arrays (NOMGAs) prepared by a metal-free procedure exhibited higher electrocatalytic activity than the commercially available Pt–C catalyst (see plot), excellent long-term stability, and resistance to crossover effects in the oxygen-reduction reaction (ORR). Graphite-like nitrogen atoms appear to be responsible for the excellent electrochemical performance in the ORR. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Basic concepts in RNA virus evolution (1996)

A hallmark of RNA genomes is the error-prone nature of their replication and retrotranscription. The major biochemical basis of the limited replication fidelity is the absence of proofreading/repair and postreplicative error correction mechanisms that normally operate during replication of cellular DNA. In spite of this unique feature of RNA replicons, the dynamics of viral populations seems to follow the same basic principles that classical population genetics has established for higher organisms. Here we review recent evidence of the profound effects that genetic bottlenecks have in enhancing the deleterious effects of Muller's ratchet during RNA virus evolution. The validity of the Red Queen hypothesis and of the competitive exclusion principle for RNA viruses are viewed as the expected result of the highly variable and adaptable nature of viral quasispecies. Viral fitness, or ability to replicate infectious progeny, can vary a million-fold within short time intervals. Paradoxically, functional and structural studies suggest extreme limitations to virus variation. Adaptability of RNA viruses appears to be based on the occupation of very narrow portions of sequence space at any given time.
A Molecular and Cellular Theory of Depression (1997)

Recent studies have begun to characterize the actions of stress and antidepressant treatments beyond the neurotransmitter and receptor level. This work has demonstrated that long-term antidepressant treatments result in the sustained activation of the cyclic adenosine 3',5'-monophosphate system in specific brain regions, including the increased function and expression of the transcription factor cyclic adenosine monophosphate response element-binding protein. The activated cyclic adenosine 3',5'-monophosphate system leads to the regulation of specific target genes, including the increased expression of brain-derived neurotrophic factor in certain populations of neurons in the hippocampus and cerebral cortex. The importance of these changes is highlighted by the discovery that stress can decrease the expression of brain-derived neurotrophic factor and lead to atrophy of these same populations of stress-vulnerable hippocampal neurons. The possibility that the decreased size and impaired function of these neurons may be involved in depression is supported by recent clinical imaging studies, which demonstrate a decreased volume of certain brain structures. These findings constitute the framework for an updated molecular and cellular hypothesis of depression, which posits that stress-induced vulnerability and the therapeutic action of antidepressant treatments occur via intracellular mechanisms that decrease or increase, respectively, neurotrophic factors necessary for the survival and function of particular neurons. This hypothesis also explains how stress and other types of neuronal insult can lead to depression in vulnerable individuals and it outlines novel targets for the rational design of fundamentally new therapeutic agents.
Design of a Robust Baseband LPC Coder for Speech Transmission Over 9.6 Kbit/s Noisy Channels (1982)

This paper describes the design of a baseband LPC coder that transmits speech over 9.6 kbit/s (kilobit/second) synchronous channels with random bit errors of up to 1 percent. Presented are the results of our investigation of a number of aspects of the baseband LPC coder with the goal of maximizing the quality of the transmitted speech. Important among these aspects are: bandwidth of the baseband, coding of the baseband residual, high-frequency regeneration, and error protection of important transmission parameters. The paper discusses these and other issues, presents the results of speech-quality tests conducted during the various stages of optimization, and describes the details of the optimized speech coder. This optimized speech coding algorithm has been implemented as a real-time full-duplex system on an array processor. Informal listening tests of the real-time coder have shown that the coder produces good speech quality in the absence of channel bit errors and introduces only a slight degradation in quality for channel bit error rates of up to 1 percent.
Distributed intelligence and modular architecture for next generation DC power system (2002)

This article describes and analyses a modular architecture for the next generation of DC power systems. It also presents the system engineering approach followed to ensure that customers requirements are all fulfilled and that the distribution of intelligence amongst the various modules is optimized.
Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. (2001)

The concept of combining chemotherapeutic agents to increase cytotoxic efficacy has evolved greatly over the past several years. The rationale for combination chemotherapy has centered, in the past, on attacking different biochemical targets, overcoming drug resistance in heterogeneous tumors, and by taking advantage of tumor growth kinetics with increasing the dose-density of combination chemotherapy. The overall goal was to improve clinical efficacy with acceptable clinical toxicity. With our increased understanding of the cell cycle and the impact chemotherapeutic agents have on the cell cycle, it is increasingly apparent that this physiology can create drug resistance, thereby reducing combination chemotherapeutic efficacy. This is particularly relevant with the advent of cell cycle-specific inhibitors but also has relevance for the action of standard chemotherapeutic agents currently in clinical practice. This cell cycle-mediated resistance may be overcome by a greater understanding of chemotherapeutic cell cycle effects and by appropriate sequencing and scheduling of agents in combination chemotherapy. In this review, we have elected to illustrate the evolving concept of cell cycle-mediated drug resistance with novel drug combinations that include the taxanes, camptothecins, and fluorouracil. This review indicates that as our understanding of the cell cycle grows, our ability to appropriately sequence chemotherapy to overcome cell cycle-mediated drug resistance can have a great impact on our therapeutic approach in the treatment of human cancers.
Detection of human speech in structured noise (2002)

This paper describes research to develop an efficient system that provides a binary decision as to the presence of speech in a short (one to three second) time sample of an acoustic signal. A method which is efficient and reliably detects human speech in the presence of structured noise (such as wind, music, traffic sounds, etc.) is described. Two separate algorithms were developed. The first algorithm detects the presence of speech by testing for concave and/or convex formant shapes. The second algorithm is a statistical pattern classifier utilizing radial basis function (RBF) networks with mel-cepstra feature vectors. Classification errors are not consistent across these two different methods. As a consequence, we plan to reduce our error rate by fusion of these methods.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>