gebhart/patrepeval huggingface dataset:
Up-Regulation of Advanced Glycated Products Receptors in the Brain of Diabetic Rats Is Prevented by Antioxidant Treatment (2005)

Diabetics have at least twice the risk of stroke and may show performance deficit in a wide range of cognitive domains. The mechanisms underlying this gradually developing end-organ damage may involve both vascular changes and direct damage to neuronal cells as a result of overproduction of superoxide by the respiratory chain and consequent oxidative stress. The study aimed to assess the role of oxidative stress on the aldose reductase-polyol pathway, on advanced glycated end-product (AGE)/AGE-receptor interaction, and on downstream signaling in the hippocampus of streptozotocin-treated rats. Data show that, in diabetic rats, levels of prooxidant compounds increase, whereas levels of antioxidant compounds fall. Receptor for AGE and galectin-3 content and polyol flux increase, whereas glyceraldehyde-3-phosphate dehydrogenase activity is impaired. Moreover, nuclear factor κB (p65) transcription factor levels and S-100 protein are increased in the hippocampus cytosol, suggesting that oxidative stress triggers the cascade of events that finally leads to neuronal damage. Dehydroepiandrosterone, the most abundant hormonal steroid in the blood, has been reported to possess antioxidant properties. When dehydroepiandrosterone was administered to diabetic rats, the improved oxidative imbalance and the marked reduction of AGE receptors paralleled the reduced activation of nuclear factor κB and the reduction of S-100 levels, reinforcing the suggestion that oxidative stress plays a role in diabetes-related neuronal damage.
Selective iron chelation in Friedreich ataxia: biologic and clinical implications (2007)

Genetic disorders of iron metabolism and chronic inflammation often evoke local iron accumulation. In Friedreich ataxia, decreased iron-sulphur cluster and heme formation leads to mitochondrial iron accumulation and ensuing oxidative damage that primarily affects sensory neurons, the myocardium, and endocrine glands. We assessed the possibility of reducing brain iron accumulation in Friedreich ataxia patients with a membrane-permeant chelator capable of shuttling chelated iron from cells to transferrin, using regimens suitable for patients with no systemic iron overload. Brain magnetic resonance imaging (MRI) of Friedreich ataxia patients compared with age-matched controls revealed smaller and irregularly shaped dentate nuclei with significantly (P < .027) higher H-relaxation rates R2*, indicating regional iron accumulation. A 6-month treatment with 20 to 30 mg/kg/d deferiprone of 9 adolescent patients with no overt cardiomyopathy reduced R2* from 18.3 s(-1) (+/- 1.6 s(-1)) to 15.7 s(-1) (+/- 0.7 s(-1); P < .002), specifically in dentate nuclei and proportionally to the initial R2* (r = 0.90). Chelator treatment caused no apparent hematologic or neurologic side effects while reducing neuropathy and ataxic gait in the youngest patients. To our knowledge, this is the first clinical demonstration of chelation removing labile iron accumulated in a specific brain area implicated in a neurodegenerative disease. The use of moderate chelation for relocating iron from areas of deposition to areas of deprivation has clinical implications for various neurodegenerative and hematologic disorders.
Improved Utility of Photolabile Solid Phase Synthesis Supports for the Synthesis of Oligonucleotides Containing 3‘-Hydroxyl Termini (1996)

Oligonucleotides are synthesized on, and cleaved from, a solid phase support (6) using the o-nitrobenzyl intramolecular photochemical redox reaction. The yields of isolated oligonucleotides relative to yields obtained using conventional hydrolytic cleavage vary between 67% and 82.5%. Synthesis of oligonucleotides using phosphoramidites that do not contain N-benzoyl protecting groups enables one to photolytically cleave the biopolymers in good yields using a commonly available UV irradiation source. Tritium labeling indicates that less than 3% thymidine.thymidine photodimers are formed during photolytic cleavage of polythymidylates from 6 using a transilluminator. No UV-induced damage is detected via HPLC analysis of enzymatically digested oligonucleotides that were obtained following photolytic cleavage from 6.
The dynamics of genome replication using deep sequencing (2013)

Eukaryotic genomes are replicated from multiple DNA replication origins. We present complementary deep sequencing approaches to measure origin location and activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number during a synchronous S-phase allowed the precise determination of genome replication. To map origin locations, replication forks were stalled close to their initiation sites; therefore, copy number enrichment was limited to origins. Replication timing profiles were generated from asynchronous cultures using fluorescence-activated cell sorting. Applying this technique we show that the replication profiles of haploid and diploid cells are indistinguishable, indicating that both cell types use the same cohort of origins with the same activities. Finally, increasing sequencing depth allowed the direct measure of replication dynamics from an exponentially growing culture. This is the first time this approach, called marker frequency analysis, has been successfully applied to a eukaryote. These data provide a high-resolution resource and methodological framework for studying genome biology.
THE LASSO METHOD FOR VARIABLE SELECTION IN THE COX MODEL (1997)

I propose a new method for variable selection and shrinkage in Cox's proportional hazards model. My proposal minimizes the log partial likelihood subject to the sum of the absolute values of the parameters being bounded by a constant. Because of the nature of this constraint, it shrinks coefficients and produces some coefficients that are exactly zero. As a result it reduces the estimation variance while providing an interpretable final model. The method is a variation of the 'lasso' proposal of Tibshirani, designed for the linear regression context. Simulations indicate that the lasso can be more accurate than stepwise selection in this setting.
Role of different proton-sensitive channels in releasing calcitonin gene-related peptide from isolated hearts of mutant mice (2004)

We conclude that cardiac acidosis is a strong stimulus to release CGRP from the mouse heart. This effect seems to be primarily mediated through activation of TRPV1 receptors that are known to be expressed by slowly conducting nociceptive primary afferent nerve fibers.
Prefetching in World Wide Web (2002)

This paper considers the use of prefetching in WWW for reducing the perceived latency. We first look at a number of basic issues and tradeoffs in prefetching. Our analysis shows that, unless the traffic is very light or the prefetching efficiency is very high, statistical prefetching may not necessarily reduce perceived delay. We then present an implementation of deterministic prefetching in a hotlist manager.
Stress in ion-exchanged glass waveguides (1986)

Stress in film and stripe waveguides, formed by ion exchange in glass, is investigated. Mechanical effects of stress, like surface damage and elevations or dips of the surface, are demonstrated. The birefringence due to stress can be varied over a wide range by varying the ion-exchange conditions.
The dystrophic hamster: an animal model of alveolar hypoventilation (1991)

The BIO 14.6 dystrophic hamster (DH) is a genetically determined animal model of alveolar hypoventilation (AH) that exhibits a ventilatory control pattern of compensation and then decompensation similar to that in progressive forms of muscular dystrophy and nonprogressive congenital myopathies in humans. Possible causes of AH in the DH include respiratory muscle weakness, ventilation-to-perfusion inequalities, and an inadequate drive to breathe. Histochemical and contractile abnormalities of the diaphragm, reduced lung surface area available for gas exchange, abnormal pulmonary microvascular reactivity to hypoxia, altered levels of neurochemicals, and abnormal cellular regulation of calcium are among the specific factors that may contribute to the development of AH. The potential role of hypothyroidism in the development of AH is reviewed because many hypothyroid patients exhibit AH and other ventilatory dysfunctions, hypothyroidism is present in human patients and animals with muscular dystrophy, and thyroid status is known to influence lung architecture, myocyte function, and neural activity. Additional studies linking neurohormonal signals, transcellular signal processing, and control of ventilation in the DH may help us understand the etiology of AH in human disease.
Towards Privacy Compliance in the Management of Raw Genomic Data (2013)

Alzheimer's Disease 'rs1799724' Susceptibility to Vascular Dementia 'rs6265' Susceptibility to Memory Impairment 'rs6265' Body Mass Index 'rs6265' Smoking behavior 'rs6265' Weight 'rs669' Alpha-2-Macroglobulin Polymorphism 'rs429358' Stroke 'rs429358' Hyperlipoproteinemia type 3 'rs429358' Brain Imaging 'rs4420638' Total Cholesterol 'rs4420638' HDL Cholesterol 'rs4420638' LDL Cholesterol 'rs4420638' Longevity 'rs4420638' Coronary Artery Disease 'rs4420638' Type II Diabetes
Effects of exercise on fitness and health of adults with spinal cord injury (2017)

Exercise improves fitness and cardiometabolic health of adults with chronic SCI. The evidence on effective exercise types, frequencies, intensities, and durations should be used to formulate exercise guidelines for adults with SCI.
Frequency, heterogeneity and encephalitogenicity of T cells specific for myelin oligodendrocyte glycoprotein in naive outbred primates (2001)

Auto-reactive T cells present in healthy subjects remain in a state of unresponsiveness, but may trigger autoimmunity under various situations. Although myelin oligodendrocyte glycoprotein (MOG) is a potential target antigen in multiple sclerosis (MS), MOG-reactive T cell responses are present in the blood of both healthy subjects and MS-affected individuals. To investigate the disease-inducing potential and regulation of these autoreactive T cells in healthy outbred populations, we have characterized MOG-reactive T cell clones obtained by limiting dilution from peripheral blood of unimmunized C. jacchus marmosets. We report an extraordinarily high prevalence of circulating MOG-reactive T cells in these naive animals (2.6 +/- 1.4 / 10(5) PBMC), and a broadly diverse repertoire of epitope recognition encompassing at least three regions within the extracellular domain of MOG. Adoptive transfer of a MOG21-40-specific T cell clone resulted in mild clinical experimental allergic encephalomyelitis, characterized pathologically by rare foci of inflammation and minimal demyelination. We conclude that MOG-reactive T cells are present in healthy primates at a highly prevalent frequency, and are potentially capable of triggering central nervous system autoimmunity. Expansion of these autoreactive T cells must be tightly controlled to maintain immune homeostasis in healthy individuals.
Protease Cleavage of Reovirus Capsid Protein μ1/μ1C Is Blocked by Alkyl Sulfate Detergents, Yielding a New Type of Infectious Subvirion Particle (1998)

Mammalian reovirus virions undergo partial disassembly of the outer capsid upon exposure to proteases in vitro, producing infectious subvirion particles (ISVPs) that lack protein sigma3 and contain protein mu1/mu1C as endoprotease-generated fragments mu1delta/delta and phi. ISVPs are thought to be required for two early steps in reovirus infection: membrane penetration and activation of the particle-bound viral transcriptase complexes. Genetic and biochemical evidence implicates outer-capsid protein mu1 in both these steps. To determine whether the cleavage of mu1/mu1C is relevant to the unique properties of ISVPs, we analyzed the properties of novel subvirion particles that lacked sigma3 yet retained mu1/mu1C in an uncleaved but cleavable form. These detergent-plus-protease subvirion particles (dpSVPs) were produced by treating virions with chymotrypsin in the presence of micelle-forming concentrations of alkyl sulfate detergents. Infections with dpSVPs in murine L or canine MDCK cells provided evidence that the cleavage of mu1/mu1C during viral entry into these cells is dispensable for reovirus infection. Additionally, dpSVPs behaved like ISVPs in their capacity to permeabilize lipid bilayers and to undergo transcriptase activation in vitro, supporting the conclusion that cleavage of mu1/mu1C to mu1delta/delta and phi during viral entry is not required for either membrane penetration or transcriptase activation in cells. The capacity of alkyl sulfate detergents to inhibit the cleavage of mu1/mu1C in a reversible fashion suggests a specific association between virus particle and detergent micelles that may mimic virus particle-phospholipid membrane interactions during reovirus entry into cells.
Inhibitory effects of Hedyotis diffusa Willd. on colorectal cancer stem cells (2016)

Cancer stem cells (CSCs) are proposed to be closely correlated with the development and progression of tumors, as well as with chemo- and radioresistance. Targeting CSCs may therefore be a promising potential strategy for the treatment of cancer. Currently, natural products have received great interest due to their therapeutic efficacy and reduced adverse effects compared with modern chemotherapeutics. As a significant component of a number of traditional Chinese medicine formulas, the medicinal herb <i>Hedyotis diffusa</i> Willd. (HDW) has long been utilized in China to clinically treat a variety of malignancies, including colorectal cancer (CRC). Previously, the authors of the present study reported that HDW suppressed CRC growth through multiple mechanisms, including promoting apoptosis, and inhibiting cell proliferation and tumor angiogenesis. To additionally investigate its mode of action, the present study isolated a stem-like side population (SP) from colorectal cancer HT-29 cells to investigate the effect of ethanol extract of HDW on CSCs. It was observed that HDW was able to markedly downregulate the expression of CSC marker leucine-rich repeat-containing G-protein coupled receptor 5 and also significantly decrease the proportion of SP in HT-29 cells, in a dose-dependent manner. Furthermore, HDW treatment significantly and dose-dependently inhibited the viability and sphere formation, and induced cell morphological changes of isolated HT-29 SP cells. In addition, HDW greatly suppressed the messenger RNA expression of several critical genes that mediate CSC features, including ATP-binding cassette, sub-family B, member 1, β-catenin, c-Myc, proliferating cell nuclear antigen and survivin. In conclusion, the present study indicates that HDW may exert inhibitory effects on cancer stem cells.
MEK inhibition impairs influenza B virus propagation without emergence of resistant variants (2004)

Influenza A and B viruses are still a major worldwide threat. We demonstrate that influenza B virus infection induces signaling via the Raf/MEK/ERK cascade, a process required for efficient virus production. Expression of dominant-negative Raf and ERK mutants or treatment with a MEK inhibitor (U0126) strongly impaired viral propagation, while selective activation of the pathway resulted in increased virus titers. MEK inhibition appears to interfere with a distinct viral nuclear export process. Most importantly, no resistant virus variants emerged in the presence of U0126 demonstrating that influenza viruses cannot easily adapt to the missing cellular function.
The Topology of the Substrate Binding Clefts of Glycosyl Hydrolase Family 10 Xylanases Are Not Conserved (1998)

The crystal structures of family 10 xylanases indicate that the distal regions of their active sites are quite different, suggesting that the topology of the substrate binding clefts of these enzymes may vary. To test this hypothesis, we have investigated the rate and pattern of xylooligosaccharide cleavage by the family 10 enzymes, Pseudomonas fluorescens subsp. cellulosa xylanase A (XYLA) and Cellulomonas fimi exoglucanase, Cex. The data showed that Cex contained three glycone and two aglycone binding sites, while XYLA had three glycone and four aglycone binding sites, supporting the view that the topologies of substrate binding clefts in family 10 glycanases are not highly conserved. The importance of residues in the substrate binding cleft of XYLA in catalysis and ligand binding were evaluated using site-directed mutagenesis. In addition to providing insight into the function of residues in the glycone region of the active site, the data showed that the aromatic residues Phe-181, Tyr-255, and Tyr-220 play important roles in binding xylose moieties, via hydrophobic interactions, at subsites +1, +3, and +4, respectively. Interestingly, the F181A mutation caused a much larger reduction in the activity of the enzyme against xylooligosaccharides compared with xylan. These data, in conjunction with a previous study (Charnock, S. J., Lakey, J. H., Virden, R., Hughes, N., Sinnott, M. L., Hazlewood, G. P., Pickersgill, R., and Gilbert, H. J. (1997) J. Biol. Chem. 272, 2942-2951), suggest that the binding of xylooligosaccharides at the -2 and +1 subsites ensures that the substrates occupy the -1 and +1 subsites and thus preferentially form productive complexes with the enzyme. Loss of ligand binding at either subsite results in small substrates forming nonproductive complexes with XYLA by binding to distal regions of the substrate binding cleft.
Phase I study of 6-diazo-5-oxo-L-norleucine (DON). (1980)

We conducted a phase I study of 6-diazo-5-oxo-L-norleucine given iv on a twice weekly schedule. Twenty-six evaluable patients received 31 courses of the drug. Doses ranged from 100 to 500 mg/m2. Nausea with vomiting was the dose-limiting toxic effect, transient thrombocytopenia was seen frequently, and mucositis occurred in 39% of the patients. No definite therapeutic responses were observed in 18 patients with measurable lesions. The recommended dose for phase II studies is 200-300 mg/m2 iv twice weekly.
Phase I study of docosahexaenoic acid-paclitaxel: a taxane-fatty acid conjugate with a unique pharmacology and toxicity profile. (2003)

The starting dose recommended for subsequent studies is 1100 mg/m(2). DHA-paclitaxel dramatically alters the PK profile of derived paclitaxel compared with values observed after a 3-h infusion of paclitaxel (175 mg/m(2)). In addition, its favorable toxicity profile offers potential advantages over existing taxanes.
l-Glutamic Acid γ-Monohydroxamate (1999)

We report that the vanadium ligand L-Glu(gamma)HXM potentiates the capacity of free vanadium ions to activate glucose uptake and glucose metabolism in rat adipocytes in vitro (by 4-5-fold) and to lower blood glucose levels in hyperglycemic rats in vivo (by 5-7-fold). A molar ratio of two L-Glu(gamma)HXM molecules to one vanadium ion was most effective. Unlike other vanadium ligands that potentiate the insulinomimetic actions of vanadium, L-Glu(gamma)HXM partially activated lipogenesis in rat adipocytes in the absence of exogenous vanadium. This effect was not manifested by D-Glu(gamma)HXM. At 10-20 microM L-Glu(gamma)HXM, lipogenesis was activated 9-21%. This effect was approximately 9-fold higher (140 +/- 15% of maximal insulin response) in adipocytes derived from rats that had been treated with vanadium for several days. Titration of vanadium(IV) with L-Glu(gamma)HXM led to a rapid decrease in the absorbance of vanadium(IV) at 765 nm, and (51)V NMR spectroscopy revealed that the chemical shift of vanadium(IV) at -490 ppm disappeared with the appearance of a signal characteristic to vanadium(V) (-530 ppm) upon adding one equivalent of L-Glu(gamma)HXM. In summary, L-Glu(gamma)HXM is highly active in potentiating vanadium-activated glucose metabolism in vitro and in vivo and facilitating glucose metabolism in rat adipocytes in the absence of exogenous vanadium probably through conversion of trace intracellular vanadium into an active insulinomimetic compound. We propose that the active species is either a 1:1 or 2:1 L-Glu(gamma)HXM vanadium complex in which the endogenous vanadium(IV) has been altered to vanadium(V). Finally we demonstrate that L-Glu(gamma)HXM- and L-Glu(gamma)HXM.vanadium-evoked lipogenesis is arrested by wortmannin and that activation of glucose uptake in rat adipocytes is because of enhanced translocation of GLUT4 from low density microsomes to the plasma membrane.
Calpains: Intact and active? (1997)

Calpains are a family of calcium-dependent thiol-proteases which are proposed to be involved in many physiological processes as well as pathological conditions. Calpains are likely to be involved in processing of numerous enzymes and cytoskeletal components, thereby linking their activity to a variety of intracellular events. Although widely studied, the precise mechanism(s) involved in calpain activation and activity in vivo remain poorly understood. Initial studies suggested that calpain exists primarily as an inactive proenzyme that required autolytic cleavage for activation. It was also hypothesized that calpain associated with membrane phospholipids, serving to increase calcium sensitivity, facilitating autolytic conversion and thus activating the enzyme. These hypotheses, however, have not been universally accepted and there is increasing evidence that intact, non-autolyzed calpain is the physiologically active calpain form.
Rapid Preparation of RNA Samples Using DNA-Affinity Chromatography and DNAzyme Methods (2012)

Milligram quantities of RNA are commonly synthesized by in vitro transcription from a DNA template with T7 RNA polymerase. However, the run-off transcription method results in heterogeneity at the RNA 3'-terminus. RNA purification requires single-nucleotide resolution to separate the transcript of the correct length from the aborted or add-on transcripts that are usually present in comparable amounts. Here, we describe an RNA preparation method that uses a trans-acting DNAzyme and sequence-specific affinity column chromatography. This purification method is simple, fast, and suited for high throughput.
Synthetic peptides corresponding to keratin subunits elicit highly specific antibodies. (1984)

The presence of common antigenic determinants within all keratin proteins has made difficult the production of antisera which are monospecific for individual keratin subunits. Synthetic peptides corresponding to the carboxyl-terminal amino acid sequences of the mouse 59- and 67-kilodalton keratins were used to produce antibodies which were highly specific for these keratin subunits. This method of antibody production was chosen after examination of amino acid sequence data (which were deduced from the nucleotide sequence of cDNA clones for these and other mouse keratins) revealed that the carboxyl-terminal amino acid sequences of various keratins were unique. Indirect immunofluorescence staining of newborn-mouse skin with these antisera demonstrated that the 59- and 67-kilodalton keratins were only present within the differentiated cells of the epidermis (the suprabasal layers) and not in the undifferentiated cells (the basal layer). These results are consistent with our previous work concerning the expression of these keratin genes at the messenger RNA level (Roop, D. R., Hawley-Nelson, P., Cheng, C. K., and Yuspa, S. H. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 716-720). Data obtained with the antisera directed against the 67-kilodalton keratin also indicated that the carboxyl-terminal sequences of this subunit were not present in the nonliving layer (the stratum corneum) of the epidermis. This approach should be useful for the production of antisera specific for other keratin subunits as additional sequence information becomes available.