gebhart/patrepeval huggingface dataset:
Transepithelial transport of glutathione in isolated perfused small intestine (1986)

Uptake of GSH was studied in isolated perfused segment of jejunum in the adult rat. Krebs-Henseleit buffer was infused through the superior mesenteric artery and fractions were collected from the portal vein. The maintenance of vascular and epithelial integrity was established by lack of transfer of /sup 14/C-inulin or /sup 14/C-polyethylene glycol from the lumen to the perfusate. (glycine-2-/sup 3/H)GSH was introduced in the lumen and perfusate fractions collected every min. With 1 mM GSH and 10 mM Gly in the lumen, transport into the perfusate was 220 nmol/min. Analysis by HPLC showed that 80% was at the intact tripeptide, GSH. No cysteinylgylcine was detected in the perfusate. Pretreatment of the segment with 0.25 mM acivicin and 1 mM buthionine sulfoximine had no significant effect on GSH transport rate, thus showing that degradation and resynthesis of GSH did not contribute to the appearance of GSH in the perfusate. GSH transport was inhibited 50% by replacing lumenal NaCl with choline Cl. Addition of 10 mM ..gamma..-Clu-Glu or 10 mM ophthalmic acid decreased the rat of transport by 60-70%. These results establish that transepithelial transport of intact GSH occurs in rat small intestine. This may allow utilization of dietary GSH or reutilizationmore » of biliary GSH. In addition, the results suggest that oral GSH may be of therapeutic benefit.« less
Translocations of 11q13 in mantle cell lymphoma fail to disrupt the S mu bp-2 gene. (1998)

We recently cloned a gene whose protein product binds to the Epstein-Barr virus BZLF1 gene promoter. The same gene has been previously cloned by another group who named it S mu bp-2 because its protein product binds to the S mu motif of the immunoglobulin heavy chain gene where it is postulated to function in immunoglobulin class switching. In the current study, we confirm that the S mu bp-2 gene is located on chromosome 11q13, a locus known to be altered by translocation in 50-70% of mantle cell lymphomas. We used Southern blot analysis to determine whether the S mu bp-2 gene was structurally rearranged in any of 25 mantle cell lymphomas. We found no evidence of rearrangement in any of these lymphomas including 18 that were proven to contain t(11;14) by cytogenetic analysis. These data suggest that structural alteration of the S mu bp-2 gene is not an underlying mechanism of tumorigenesis in mantle cell lymphomas.
Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea (2012)

Inner ear hair cells are specialized sensory cells essential for auditory function. Previous studies have shown that the sensory epithelium is postmitotic, but it harbors cells that can behave as progenitor cells in vitro, including the ability to form new hair cells. Lgr5, a Wnt target gene, marks distinct supporting cell types in the neonatal cochlea. Here, we tested the hypothesis that Lgr5(+) cells are Wnt-responsive sensory precursor cells. In contrast to their quiescent in vivo behavior, Lgr5(+) cells isolated by flow cytometry from neonatal Lgr5(EGFP-CreERT2/+) mice proliferated and formed clonal colonies. After 10 d in culture, new sensory cells formed and displayed specific hair cell markers (myo7a, calretinin, parvalbumin, myo6) and stereocilia-like structures expressing F-actin and espin. In comparison with other supporting cells, Lgr5(+) cells were enriched precursors to myo7a(+) cells, most of which formed without mitotic division. Treatment with Wnt agonists increased proliferation and colony-formation capacity. Conversely, small-molecule inhibitors of Wnt signaling suppressed proliferation without compromising the myo7a(+) cells formed by direct differentiation. In vivo lineage tracing supported the idea that Lgr5(+) cells give rise to myo7a(+) hair cells in the neonatal Lgr5(EGFP-CreERT2/+) cochlea. In addition, overexpression of β-catenin initiated proliferation and led to transient expansion of Lgr5(+) cells within the cochlear sensory epithelium. These results suggest that Lgr5 marks sensory precursors and that Wnt signaling can promote their proliferation and provide mechanistic insights into Wnt-responsive progenitor cells during sensory organ development.
Commentary on the Phototoxicity and Absorption of Vitamin B2 and Its Degradation Product, Lumichrome (2015)

In this commentary, we present two views related to the study of riboflavin (vitamin B 2 ): (i) future research into the photo toxicity of riboflavin and its photo-degradation product, lumichrome, should consider effects under visible light and ultraviolet (UV) light in skin because the photochemistry of these reactions differ; and (ii) future research should consider the possibility that excess lumichrome, which is metabolized from riboflavin by intestinal bacteria and is much less water-soluble than riboflavin, could be more readily absorbed and lead to symptoms that resemble those of fat-soluble vitamins.
Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas (1990)

Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps.
Mechanical Properties of the Myotomal Musculo-Skeletal System of Rainbow Trout, Salmo Gairdneri (1985)

Net forces and velocities resulting from in situ contractions of the myotomal musculature on one side of the body were measured at the hypural bones. Forces, velocities and power were determined with the body bent into a range of postures typical of those observed during fast-start swimming. For trout averaging 0.178 m in length and 0.0605 kg in body mass, the muscle system exerts a maximum normal force of 2.2N at the base of the caudal fin. This force is equivalent to 11.8 kN m-2 based on the mean cross-sectional area of the myotomal muscle. The maximum velocity was 1.11 m s-1, and the maximum mechanical power output, 0.64 W, or 42.4 W kg-1 muscle. Based on estimates of swimming resistance, these results would suggest acceleration rates of 7.5 to 16.5 m s-2, similar to averages observed during fast-starts. Maximum sprint speeds would range from 6.5 to 17.8 body lengths s-1, spanning the range of maximum speeds reported in the literature. It is suggested that maximum speed is limited by interactions between muscle contraction frequency and endurance. Losses in the mechanical linkages between muscle fibres and propulsive surfaces were estimated at about 50% for power with possibly greater losses in force transmission. Maximum force and power did not vary over the range of postures tested, supporting Alexander's (1969) suggestions that white muscle should contract over a small portion of the resting length of the fibres.
A dual-polarized W-band metal patch antenna element for phased array applications (2014)

This paper describes results of measurements of a 2×2 `unit cell' of dual-polarized metal patch elements intended for electronically scanned array applications. The unit cell is the fundamental building block of a linear array feed to a cylindrical parabolic reflector. The transmit and receive elements are arranged on a triangular grid which provides good isolation between separate transmit and receive modules, obviating the need for circulators. The 2×2 unit cell and associated feed network was implemented in PolyStrata <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">®</sup> technology. Measurements agree very well with simulations in HFSS, with the overall loss of the element and interconnect estimated as 0.5dB at 94 GHz.
Intelligent parking method for trailers in presence of fixed and moving obstacles (2010)

A Fuzzy approach to backward movement control for trailers in a dynamic environment is presented in this paper. The approach is then extended and employed for conditions where obstacles are placed on the trailer pathway. In the first case, obstacles are assumed to be fixed, while the second condition includes moving obstacles through which the trailer should be directed toward the parking dock. The method is designed in a way to be used in conditions with infinite number of obstacles at arbitrary places. In any case, to find the parking dock, the trailer movement must be adapted to that of obstacles. In the present paper, two separate fuzzy controllers are used for directing the trailer: one for finding the target, and the other for avoiding the obstacles. While there is no obstacle around, the target finder controller is in use; and in the cases where the trailer gets close to obstacles the obstacle avoider controller is activated. The proposed method is employed for parking a trailer model through fixed and moving obstacles.
Robust training algorithm for a perceptron neuron (2002)

Our interest in this paper is to study the behavior of the perceptron neuron in the presence of disturbance which is always important for practical applications. A robust classifier is required to be insensitive to disturbances and to classify noisy input patterns into the correct class, to which the respective desired input pattern belongs. The projection algorithm with a dead zone is well known in system identification and adaptive control systems to guarantee the convergence. In this paper, the dead zone scheme is used to train the nonlinear perceptron neuron. The trained perceptron neuron is capable of classifying the noisy input pattern sequence into the correct class in the presence of disturbance.
Pregabalin: a new anxiolytic (2003)

Pregabalin (S-[+]-3-isobutylgaba) was designed as a lipophilic GABA (gamma-aminobutyric acid) analogue substituted at the 3'-position in order to facilitate diffusion across the blood-brain barrier. It was originally developed as an anticonvulsant agent, however it has been shown to be effective in the treatment of several disorders including hyperalgesia and behavioural disorders. Although its exact mode of action remains unclear, pregabalin interacts with the same binding site and has a similar pharmacological profile as its predecessor, gabapentin (1-[aminomethyl] cyclohexane acetic acid). Its main site of action appears to be on the alpha(2)delta subunit of voltage-dependent calcium channels, widely distributed throughout the peripheral and central nervous system. Pregabalin appears to produce an inhibitory modulation of neuronal excitability. In healthy volunteers, it is rapidly absorbed with peak blood concentrations within 1 h and it has a bioavailability of approximately 90%. In preclinical trials of anticonvulsant activity, pregabalin is three to ten times more potent than gabapentin. It is well-tolerated and associated with dose-dependent adverse effects (ataxia, dizziness, headache and somnolence) that are mild-to-moderate and usually transient. There are no known pharmacokinetic drug-drug interactions reported to date. Preliminary animal and human studies showed beneficial effects in both ethological and conflict models of anxiety, as well as having some sleep-modulating properties. In Phase II and III trials, pregabalin shows promising anxiolytic action when compared to placebo in generalised anxiety disorder, social phobia and panic disorder.
Evaluation of toxicity and antitumor activity of cycloviolacin O2 in mice (2010)

Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v., 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v., 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC5o values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2-3 days; lower doses were without complications.
Discovering Semantic Web Services with and without a Common Ontology Commitment (2006)

This paper presents an algorithm to match a semantic Web service request against semantic Web service advertisements. The algorithm is to be used by systems to discover semantic Web services, such as the UDDI. Matching is based on the assessment of the similarity among semantic Web service properties, such as inputs and outputs. Semantic Web services have their inputs and outputs annotated or described by ontological concepts. The algorithm is able to match a semantic Web service request against advertisements that are annotated with concepts with and without a common ontology commitment. The similarity of inputs and outputs is evaluated based on concepts (classes), their semantic relations, and their common and distinguishing features (properties)
Quality of life differs among headache diagnoses: analysis of SF-36 survey in 901 headache patients (2001)

This paper presents the results of health-related quality of life (HRQoL) in 901 patients consecutively visiting a headache clinic of a national medical center in Taipei, Taiwan. HRQoL was evaluated with the Medical Outcome Study-Short Form (SF-36) and the Hospital Anxiety and Depression Scale (HADS). According to the classification criteria for chronic daily headache (CDH) proposed by Silberstein et al. (Neurology 47 (1996) 871) five hundred and ninety-three (66%) patients had CDH, of whom transformed migraine (TM) was diagnosed in 310, and chronic tension-type headache (CTTH) in 231. One hundred and ninety-three patients had episodic migraine. All SF-36 scale scores significantly correlated with the HADS scores and the intensity and frequency of pain. Compared with the normative data, a pervasive multi-dimensional decline of the SF-36 scores was noted among the headache patients except for the physical functioning scale. The decline was most remarkable in the role limitations of physical and emotional dimensions and in the bodily pain. An increasing impairment of the SF-36 scores was noted from migraine to CTTH to TM. After controlling for the HADS, age, gender, education, and chronic illness by multiple linear regression analyses, the patients with TM had the worst SF-36 profile; whereas, the patients with CTTH and migraine had compatible results. This study is the first to demonstrate that the SF-36 scores differ among headache diagnoses. Psychological distress, as well as the percentages of the types of patients, greatly influenced the SF-36 scores in hospital-based headache samples. Our findings also suggest that improvement in the pain profile as well as psychological well-being can predict a generalized improvement in the SF-36 scales in headache patients.
Low Serum Testosterone and Estradiol Predict Mortality in Elderly Men (2009)

Elderly men with low serum testosterone and estradiol have increased risk of mortality, and subjects with low values of both testosterone and estradiol have the highest risk of mortality.
A study of Src SH2 domain protein-phosphopeptide binding interactions by electrospray ionization mass spectrometry (1997)

The noncovalent binding of various peptide ligands to pp60src (Src) SH2 (Src homology 2) domain protein (12.9 ku) has been used as a model system for development of electrospray ionization mass spectrometry (ESI-MS) as a tool to study noncovalently bound complexes. SH2 motifs in proteins are critical in the signal transduction pathways of the tyrosine kinase growth factor receptors and recognize phosphotyrosine-containing proteins and peptides. ESI-MS with a magnetic sector instrument and array detection has been used to detect the protein-peptide complex with low-picomole sensitivity. The relative abundances of the multiply charged ions for the complex formed between Src SH2 protein and several nonphosphorylated and phosphorylated peptides have been compared. The mass spectrometry data correlate well to the measured binding constants derived from solution-based methods, indicating that the mass spectrometry-based method can be used to assess the affinity of such interactions. Solution-phase equilibrium constants may be determined by measuring the amount of bound and unbound species as a function of concentration for construction of a Scatchard graph. ESI-MS of a solution containing Src SH2 with a mixture of phosphopeptides showed the expected protein-phosphopeptide complex as the dominant species in the mass spectrum, demonstrating the method’s potential for screening mixtures from peptide libraries.
KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs (2013)

Epigenetic mechanisms mediate heritable control of cell identity in normal cells and cancer. We sought to identify epigenetic regulators driving the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal human cancers. We found that KDM2B (also known as Ndy1, FBXL10, and JHDM1B), an H3K36 histone demethylase implicated in bypass of cellular senescence and somatic cell reprogramming, is markedly overexpressed in human PDAC, with levels increasing with disease grade and stage, and highest expression in metastases. KDM2B silencing abrogated tumorigenicity of PDAC cell lines exhibiting loss of epithelial differentiation, whereas KDM2B overexpression cooperated with KrasG12D to promote PDAC formation in mouse models. Gain- and loss-of-function experiments coupled to genome-wide gene expression and ChIP studies revealed that KDM2B drives tumorigenicity through 2 different transcriptional mechanisms. KDM2B repressed developmental genes through cobinding with Polycomb group (PcG) proteins at transcriptional start sites, whereas it activated a module of metabolic genes, including mediators of protein synthesis and mitochondrial function, cobound by the MYC oncogene and the histone demethylase KDM5A. These results defined epigenetic programs through which KDM2B subverts cellular differentiation and drives the pathogenesis of an aggressive subset of PDAC.
Intramuscular Immunization of Mice with Irradiated Plasmodium Berghei Sporozoites (1975)

These studies have confirmed a previous report which demonstrated that intramuscularly injected irradiated sporozoites of Plasmodium berghei are far less effective than those injected intravenously in protectively immunizing mice against sporozoite-induced malaria. Because albumin has been shown to induce motility in Plasmodium sporozoites, attempts were made to determine whether the use of albumin in immunizing inocula given intramuscularly might enhance the protection thus obtained. The results showed that albumin did indeed significantly enhance the development of protective immunity, though this protection was still considerably less than that obtained by intravenous immunization. This effect of albumin may be due to its ability to induce motility in the injected sporozoites, thereby permitting them to reach and enter blood vessels more readily.
Cannabinoids Induce Cancer Cell Proliferation via Tumor Necrosis Factor α-Converting Enzyme (TACE/ADAM17)-Mediated Transactivation of the Epidermal Growth Factor Receptor (2004)

Cannabinoids, the active components of marijuana and their endogenous counterparts were reported as useful analgetic agents to accompany primary cancer treatment by preventing nausea, vomiting, and pain and by stimulating appetite. Moreover, they have been shown to inhibit cell growth and to induce apoptosis in tumor cells. Here, we demonstrate that anandamide, Delta(9)-tetrahydrocannabinol (THC), HU-210, and Win55,212-2 promote mitogenic kinase signaling in cancer cells. Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity. EGFR signal transactivation was identified as the mechanistic link between cannabinoid receptors and the activation of the mitogen-activated protein kinases extracellular signal-regulated kinase 1/2 as well as prosurvival protein kinase B (Akt/PKB) signaling. Depending on the cellular context, signal cross-communication was mediated by shedding of proAmphiregulin (proAR) and/or proHeparin-binding epidermal growth factor-like growth factor (proHB-EGF) by tumor necrosis factor alpha converting enzyme (TACE/ADAM17). Taken together, our data show that concentrations of THC comparable with those detected in the serum of patients after THC administration accelerate proliferation of cancer cells instead of apoptosis and thereby contribute to cancer progression in patients.
Detection of BK virus and simian virus 40 in the urine of healthy children (2005)

Seroprevalence studies indicate that most primary infections with BK virus (BKV) and JC virus (JCV) occur in the first and second decades of life, respectively. Relatively little is known about the transmission of these agents, including the primary source of human exposure, the portal of entry, and the pathophysiology of life-long viral persistence. We sought to determine if simian virus 40 (SV40) excretion could be detected in the urine of healthy children and to define the age-related prevalence of polyomavirus shedding in this population. A point prevalence study of polyomavirus shedding was conducted in healthy children using rigorous enrollment criteria. Urine samples were collected from healthy children, age from 3 to 18 years, during routine evaluation at two urban pediatric clinics. Qualitative PCR analysis was performed using primers that detect a conserved region of the T-antigen gene of BKV, JCV, and SV40. The identity of polyomaviruses detected was determined by DNA sequence analysis and/or PCR amplification of other regions of the viral genomes. Seven of 72 (9.7%) urine samples were positive for polyomaviruses: three with BKV (ages 4, 6, 13), two with SV40 (ages 6, 16), two with BKV and SV40 co-excretion (ages 6, 15), and none with JCV. DNA sequence analysis confirmed the identity of viruses detected. These results suggest that the timing of SV40 infections in humans may be similar to that of BKV and that urine from healthy children could contribute to the ubiquity of BKV infection early in life.