gebhart/patrepeval huggingface dataset:
Antiepileptic drug development program. (1983)

The Epilepsy Branch of the National Institute of Neurological and Communicative Disorders and Stroke has responded to the need for new, more effective, and less toxic antiepileptic drugs by cooperating with pharmaceutical companies in key areas of development. The ADD Program screens large numbers of compounds for anticonvulsant activity in appropriate animal models and sponsors clinical trials of promising new drugs for the treatment of epilepsy. The use of investigative techniques developed since the late 1960s allows documentation of seizure type and seizure frequency for maximal objectivity of clinical trial data.
Accurate Random Coil Chemical Shifts from an Analysis of Loop Regions in Native States of Proteins (2009)

We present a method for calculating accurate random coil chemical shift values of proteins. These values are obtained by analyzing the relationship between the amino acid sequences in flexible loop regions of native states and the corresponding experimentally measured chemical shifts. We estimate the errors in the random coil chemical shift scales to be 0.31 ppm for (13)C(alpha), 0.37 ppm for (13)C(beta), 0.31 ppm for (13)CO, 0.68 ppm for (15)N, 0.09 ppm for (1)H, and 0.04 ppm for (1)H(alpha).
High-Throughput Genomic and Proteomic Analysis Using Microarray Technology (2001)

The integrated microarray technology platform is adaptable and versatile, while offering the high-throughput capabilities needed for drug development and discovery applications.
Identification of a novel sulfonated oxysterol, 5-cholesten-3β,25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria (2006)

This study reports the discovery of a novel sulfonated oxysterol found at high levels in the mitochondria and nuclei of primary rat hepatocytes after overexpression of the gene encoding steroidogenic acute regulatory protein (StarD1). Forty-eight hours after infection of primary rat hepatocytes with recombinant adenovirus encoding StarD1, rates of bile acid synthesis increased by 4-fold. Concurrently, [(14)C]cholesterol metabolites (oxysterols) were increased dramatically in both the mitochondria and nuclei of StarD1-overexpressing cells, but not in culture medium. A water-soluble [(14)C]oxysterol product was isolated and purified by chemical extraction and reverse-phase HPLC. Enzymatic digestion, HPLC, and tandem mass spectrometry analysis identified the water-soluble oxysterol as 5-cholesten-3beta,25-diol 3-sulfonate. Further experiments detected this cholesterol metabolite in the nuclei of normal human liver tissues. Based upon these observations, we hypothesized a new pathway by which cholesterol is metabolized in the mitochondrion.
Induced pluripotency: history, mechanisms, and applications (2010)

The generation of induced pluripotent stem cells (iPSCs) from somatic cells demonstrated that adult mammalian cells can be reprogrammed to a pluripotent state by the enforced expression of a few embryonic transcription factors. This discovery has raised fundamental questions about the mechanisms by which transcription factors influence the epigenetic conformation and differentiation potential of cells during reprogramming and normal development. In addition, iPSC technology has provided researchers with a unique tool to derive disease-specific stem cells for the study and possible treatment of degenerative disorders with autologous cells. In this review, we summarize the progress that has been made in the iPSC field over the last 4 years, with an emphasis on understanding the mechanisms of cellular reprogramming and its potential applications in cell therapy.
Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics (2003)

Anesthetics exert multiple effects on the central nervous system through altering synaptic transmission, but the mechanisms for this process are poorly understood. PDZ domain-mediated protein interactions play a central role in organizing signaling complexes around synaptic receptors for efficient signal transduction. We report here that clinically relevant concentrations of inhalational anesthetics dose-dependently and specifically inhibit the PDZ domain-mediated protein interaction between PSD-95 or PSD-93 and the N-methyl-d-aspartate receptor or neuronal nitric-oxide synthase. These inhibitory effects are immediate, potent, and reversible and occur at a hydrophobic peptide-binding groove on the surface of the second PDZ domain of PSD-95 in a manner relevant to anesthetic action. These findings reveal the PDZ domain as a new molecular target for inhalational anesthetics.
Characterization of naturally processed antigen bound to major histocompatibility complex class II molecules. (1991)

Helper T lymphocytes recognize peptide fragments of antigen bound to major histocompatibility complex (MHC) class II molecules presented on the surface of antigen-presenting cells (APCs). Previous studies showed that the MHC class II, I-Ek molecules purified from APCs that had processed Drosophila melanogaster cytochrome c (DMc) contained functional, processed antigen-I-Ek complexes. This was demonstrated by the ability of purified I-Ek, incorporated into liposomes, to stimulate DMc-specific T cells in the absence of any additional antigen. Here we describe the isolation and characterization of the processed antigen bound to I-Ek. This was accomplished using DMc radiolabeled across its entire length by reductive methylation of its lysine residues, allowing an analysis of the totality of processed antigen bound to MHC class II molecules. After processing, only about 0.2% of the APC I-Ek molecules contained processed DMc (approximately 800 per cell), yet these were sufficient to stimulate specific T cells. The DMc peptides isolated from the I-Ek molecules showed only two predominant radioactive peaks as analyzed by reverse-phase chromatography. Less processed antigen was bound to purified I-Ak molecules, and these peptides were distinct from those bound to I-Ek. The association of processed DMc with the I-Ek and I-Ak molecules appears highly specific in that no radiolabeled peptides were isolated from purified MHC class I molecules, Kk and Dk, or from the B-cell differentiation antigen B220. The majority of processed antigen-I-Ek complexes migrated more slowly than the majority of the I-Ek protein as analyzed by SDS/PAGE under nonreducing conditions without heating of the sample. This form of I-Ek may be analogous to the earlier described "floppy" form of MHC class II molecules [Dormair, K., Rothenhausler, B. & McConnell, H. M. (1990) Cold Spring Harbor Symp. Quant. Biol. 54, 409-416]. Since newly processed antigen binds nearly exclusively to this slow-migrating form, it may be of functional significance.
Nonlinear approximation based image recovery using adaptive sparse reconstructions and iterated denoising-part II: adaptive algorithms (2006)

We combine the main ideas introduced in Part I with adaptive techniques to arrive at a powerful algorithm that estimates missing data in nonstationary signals. The proposed approach operates automatically based on a chosen linear transform that is expected to provide sparse decompositions over missing regions such that a portion of the transform coefficients over missing regions are zero or close to zero. Unlike prevalent algorithms, our method does not necessitate any complex preconditioning, segmentation, or edge detection steps, and it can be written as a progression of denoising operations. We show that constructing estimates based on nonlinear approximants is fundamentally a nonconvex problem and we propose a progressive algorithm that is designed to deal with this issue directly. The algorithm is applied to images through an extensive set of simulation examples, primarily on missing regions containing textures, edges, and other image features that are not readily handled by established estimation and recovery methods. We discuss the properties required of good transforms, and in conjunction, show the types of regions over which well-known transforms provide good predictors. We further discuss extensions of the algorithm where the utilized transforms are also chosen adaptively, where unpredictable signal components in the progressions are identified and not predicted, and where the prediction scenario is more general.
An Analysis of Acute Changes in Interleukin-6 Levels After Treatment of Hepatitis C with Consensus Interferon (2001)

Cytokine production has been implicated in the antiviral response to interferon-alpha (IFN-alpha) in hepatitis C and in the development of IFN-alpha-related side effects. We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN (IFN-con1) and during continuous treatment of chronic hepatitis C patients. Serum samples were collected at baseline, at multiple times early after IFN administration, and weekly thereafter. Viral RNA titers were assessed by RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, and IL-16. Serum cytokine levels were low at baseline. IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR, indicating that low levels of circulating IL-6 were associated with hepatitis C infection. None of the cytokines measured increased significantly after IFN administration except for IL-6. IL-6 levels rose rapidly, peaked at 6-15 h in a dose-dependent manner, and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment. This was confirmed by RT-PCR. Pretreatment IL-6 levels were directly correlated with area under the curve (AUC) for IL-6 during the 24 h after IFN dosing (r = 0.611, p = 0.007). Viral titers decreased within 24-48 h after a single dose of IFN-con1. Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels. In conclusion, (1) baseline serum cytokine levels, except for IL-6, were low or within the normal range in patients with hepatitis C, (2) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls, (3) IL-6 levels increased acutely after a single dose of IFN-alpha, and IL-6 induction was related to baseline IL-6 level, and (4) changes in IL-6 levels did not correlate with the early virologic response to IFN.
An integrated approach to encrypting scalable video (2003)

Scalable video compression is the encoding of a single video stream in multiple layers, each layer with its own bit rate. Because of the computational complexity of full video encryption, partial encryption has emerged as a general trend for both standard and scalable video codecs. Depending on the application, a particular layer of the video stream is chosen for encryption. In some applications, however, more than one video layer may need to be protected. This results in a more complicated key management as multiple keys are needed. In this paper, we present an integrated approach to encrypting multiple layers. Our proposal is a prepositioned shared secret scheme that enables the reconstruction of different keys by communicating different activating shares for the same prepositioned information. It presents certain advantages over three other key management schemes.
The search for compounds that stimulate thermogenesis in obesity management: from pharmaceuticals to functional food ingredients (2011)

The concept of managing obesity through the stimulation of thermogenesis is currently a focus of considerable attention by the pharmaceutical, nutraceutical and functional food industries. This paper first reviews the landmark discoveries that have fuelled the search for thermogenic anti-obesity products that range from single-target drugs to multi-target functional foods. It subsequently analyses the thermogenic and fat-oxidizing potentials of a wide array of bioactive food ingredients which are categorized under methylxanthines, polyphenols, capsaicinoids/capsinoids, minerals, proteins/amino acids, carbohydrates/sugars and fats/fatty acids. The main outcome of this analysis is that the compounds or combination of compounds with thermogenic and fat-oxidizing potentials are those that possess both sympathomimetic stimulatory activity and acetyl-coA carboxylase inhibitory property, and are capable of targeting both skeletal muscle and brown adipose tissue. The thermogenic potentials of products so far tested in humans range from marginal to modest, i.e. 2-5% above daily energy expenditure. With an increasing number of bioactive food ingredients awaiting screening in humans, there is hope that this thermogenic potential could be safely increased to 10-15% above daily energy expenditure - which would have clinically significant impact on weight management, particularly in the prevention of obesity and in improving the long-term prognosis of post-slimming weight maintenance.
Clinical significance of the ubiquitin ligase UBE3C in hepatocellular carcinoma revealed by exome sequencing (2014)

Our findings indicate that UBE3C is a candidate oncogene involved in tumor development and progression and therefore a potential therapeutic target in applicable HCC patients.
Electronic government: Understanding factors affecting citizen adoption in Papua New Guinea using the UTAUT (2015)

The rapid advancement of information and communication technology (ICT) and the Internet technologies is enabling e-government to provide a way for governments to improve their operational activities to serve their clients more efficiently. In developing countries, adoption of egovernment is being affected by various factors. Understanding and addressing these factors is essential for Papua New Guinea (PNG) to successfully implement and use e-government services. This paper discusses the Unified Theory of Acceptance and Use of Technology (UTAUT), which could be used to examine the factors that are influencing adoption of e-government by citizens in PNG and how these factors might be addressed.
Blood monocytes, myeloid dendritic cells and the cytokines interleukin (IL)‐7 and IL‐15 maintain human CD4+ T memory cells with mixed helper/regulatory function* (2006)

The number and function of human T cells in the periphery are regulated by homeostatic signals received from antigen-presenting cells (APCs) and the common gamma chain (gammac) cytokines interleukin (IL)-7 and IL-15. We found that, in the absence of introduced antigen, blood monocytes or myeloid dendritic cells (MDCs) in the presence of IL-7 and IL-15 (IL-7/IL-15) can regulate CD4(+) T memory (Tm) cell numbers by polyclonal cell proliferation. The dynamics of CD4(+) Tm cell proliferation, in the presence of IL-7/IL-15, was dependent on contact with MDCs and to a lesser extent on contact with monocytes. IL-7/IL-15 either alone or combined with monocytes or MDCs enhanced the proportion of CD4(+) Tm cells with activated and effector phenotype and diminished the helper function of CD4(+) Tm cells. These CD4(+) Tm cells, preconditioned with IL-7/IL-15 alone or with monocytes or MDCs and IL-7/IL-15, reduced T cell-dependent immunoglobulin M (IgM) and IgG responses. This appeared to be a contact-dependent effect involving a reduction in antibody-producing CD27(+) B memory cells, but contact-independent suppression by soluble factors also contributed to the antibody-producing capacity of CD27(+) B memory cells. These results indicate that blood monocytes, MDCs and the cytokines IL-7/IL-15 contribute to homeostasis of CD4(+) Tm cells by regulating their number, activation state and helper/suppressor (regulatory) function. In healthy individuals, this mode of regulating CD4(+) Tm cell homeostasis may provide a basis for the control of autoimmune responses.
Carbodiimide-Mediated Coupling of Benzenepentacarboxylate to Human Hemoglobin: Structural and Functional Consequences (1992)

We have examined the covalent modification of HbA with BPC (benzenepentacarboxylate) whose carboxyl groups were activated with EDC [1-ethyl-3-(3-dimethyl- aminopropyl)-carbodiimide]. Reaction of deoxy-HbA at pH 8 with a 10-fold excess of BPC, preactivated with a 2-fold excess of EDC for 5 minutes, followed by anion-exchange chromatography, gives three components with p50 values of 1.15 (unreacted HbA), 11.7 and 7.6 mm of Hg at 20 degrees C (50 mM Bis-Tris pH 7.0). Component III does not dissociate into dimers upon dilution, but components I and II do. When deoxy-HbA is reacted at pH 6 with 10-fold BPC, preactivated with two-fold EDC for 5 minutes, the resultant HbA derivatives can be separated into three components, with p50 values at pH 7 of 14.2, 10.2 and 5.2 mm of Hg, respectively. All three components are stable tetramers. Oxygen binding by all of the covalent HbA-(BPC)x complexes is cooperative, pH sensitive, but IHP insensitive. The latter observation suggest that BPC is covalently bound to HbA's DPG/IHP binding site. This conclusion is corroborated by reversed phase HPLC analysis which shows that all five modified HbAs contain at least one modified beta chain. In addition, 4 of the 5 derivatives also contain modified alpha chains. No inter or intratetramer crosslinks are observed.
The structure and function of cutaneous sensory receptors. (1988)

The present review of cutaneous sensory receptors begins with a consideration of free nerve endings (FNEs) that can be considered as sensory terminals evidencing the least structural specialization of the axon and associated cells. Using the criteria established by Kruger et al (1981), FNEs of both A delta and C fibers can be identified on the basis of ultrastructural characteristics that include an intimate relationship between axons and the associated epithelium, the lack of a complete Schwann cell investment, the accumulation of numerous vesicles and other cytoplasmic organelles, and for A delta terminals a 1:1 relationship between axon and investing Schwann cell. Using these criteria, the so-called genital end bulbs of the human glans penis are merely a skein of FNEs based on the ultrastructural study of Halata and Munger (1986). Hair follicles of most species studied to date (the exception being the rabbit and to some extent the guinea pig) are multiply innervated with lanceolate, Ruffini and FNEs. The lanceolate terminals are the rapidly adapting terminals that are numerous in guard hairs. Ruffini terminals of hairs resemble those of the periodontal ligament or joint capsules and both are remarkably similar to Golgi tendon organs in terms of ultrastructural characteristics. The key ultrastructural characteristic is the encircling of collagen bundles by axons and associated Schwann and connective tissue cells. Axons frequently enter the epidermis either to terminate as FNEs or become associated with Merkel cells in glabrous skin at the base of the papillary ridges or in clusters of Merkel cells in hairy skin in touch domes or Haarscheiben. Merkel cells have clusters of apparent secretory granules polarized toward the axon and the axon is typically a slowly adapting mechanoreceptor. The function of the granules is not known. Pacinian corpuscles are the largest of the corpuscular receptors of the dermis and are characterized by an elaborate inner core of stacks of numerous thin lamellae arranged in a bilaterally symmetrical manner. Based on the fact that the lamellae are coupled with gap junctions and the outer core lamellae isolated by numerous tight junctions, the authors have proposed that the unique ionic environment may be in part responsible for the remarkable sensitivity of Pacinian corpuscles (Munger and Ide, 1987). Meissner corpuscles are a typical corpuscular receptor of murine (Ide, 1976, 1977), marsupial and primate glabrous skin (Munger, 1971). The axons typically weave back and forth between stacks of lamellae.(ABSTRACT TRUNCATED AT 400 WORDS)
Emerging Infectious Diseases in the United States, 1993 (1994)

Three outbreaks of disease in the United States in 1993 caused by Escherichia coli O157:H7, Cryptosporidium organisms, and a previously unrecognized hantavirus clearly illustrate the increasing challenges posed by emerging infectious diseases. The largest US outbreak of E. coli O157:H7 infection reported occurred as a result of contaminated hamburgers served at a fast-food restaurant chain. The largest recorded waterborne disease outbreak in US history was due to contamination of a municipal water supply with cryptosporidia. In the southwestern United States, hantavirus was first recognized as the cause of a pulmonary syndrome with a mortality rate exceeding 50%. The detection of and response to these outbreaks document the need for a strong partnership between the clinical and public health sectors to prevent and control diseases. Health care reform in the United States provides an opportunity to address critical needs, such as improved surveillance and diagnosis, to ensure timely detection of and rapid response to newly emerging infectious diseases.
Simultaneous Fermentation of Glucose and Xylose to Butanol by Clostridium sp. Strain BOH3 (2014)

Cellulose and hemicellulose constitute the major components in sustainable feedstocks which could be used as substrates for biofuel generation. However, following hydrolysis to monomer sugars, the solventogenic Clostridium will preferentially consume glucose due to transcriptional repression of xylose utilization genes. This is one of the major barriers in optimizing lignocellulosic hydrolysates that produce butanol. Unlike studies on existing bacteria, this study demonstrates that newly reported Clostridium sp. strain BOH3 is capable of fermenting 60 g/liter of xylose to 14.9 g/liter butanol, which is similar to the 14.5 g/liter butanol produced from 60 g/liter of glucose. More importantly, strain BOH3 consumes glucose and xylose simultaneously, which is shown by its capability for generating 11.7 g/liter butanol from a horticultural waste cellulosic hydrolysate containing 39.8 g/liter glucose and 20.5 g/liter xylose, as well as producing 11.9 g/liter butanol from another horticultural waste hemicellulosic hydrolysate containing 58.3 g/liter xylose and 5.9 g/liter glucose. The high-xylose-utilization capability of strain BOH3 is attributed to its high xylose-isomerase (0.97 U/mg protein) and xylulokinase (1.16 U/mg protein) activities compared to the low-xylose-utilizing solventogenic strains, such as Clostridium sp. strain G117. Interestingly, strain BOH3 was also found to produce riboflavin at 110.5 mg/liter from xylose and 76.8 mg/liter from glucose during the fermentation process. In summary, Clostridium sp. strain BOH3 is an attractive candidate for application in efficiently converting lignocellulosic hydrolysates to biofuels and other value-added products, such as riboflavin.