gebhart/patrepeval huggingface dataset:
Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term (2000)

Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy.
Interferon-gamma receptors on T cells in patients with chronic liver disease. (1988)

Interferon-gamma (IFN-gamma) appears to be important for the activation of T cells, and its binding to IFN-gamma receptors on T cells is an essential step for its actions. We investigated the expression of IFN-gamma receptors on T cells in chronic liver disease using radioiodinated recombinant interferon-gamma binding assay, and by Scatchard analysis. The mean numbers of IFN-gamma receptors on T cells from controls, asymptomatic hepatitis B virus carriers (ASC), patients with chronic active hepatitis (CAH), and patients with liver cirrhosis (LC) were 2,205 +/- 497, 2,494 +/- 1,074, 1,925 +/- 735, and 1,666 +/- 653, respectively. The numbers of IFN-gamma receptors on T cells from the patients with LC were significantly smaller than those of controls (P less than 0.05). Kids of IFN-gamma receptor on T cells from control and patient groups were 2.3 4.8 x 10(-9) M, and there was no significant difference among the groups. The percentage of T cells reactive with OKT3, OKT4, or OKT8 was similar in control and patient groups. These findings suggest that the decrease in IFN-gamma receptors in LC is not related to the activity of the liver damage, but is associated with the severity of the underlying disease. The normal expression of IFN-gamma receptors on T cells from CAH may provide a reasonable basis for IFN-gamma therapy to type B CAH.
Interleukin 10 reduces mortality from severe peritonitis in mice (1995)

Interleukin 10 (IL-10) is known to suppress the induction of proinflammatory cytokines such as tumor necrosis factor (TNF) and IL-1 and is itself induced by monocytes and macrophages during sepsis. We studied the therapeutic efficacy of IL-10 by testing its effect on the survival rate in the murine cecal ligation-and-puncture (CLP) model. Administration of 1 microgram or more of recombinant murine IL-10 6 h after induction of sepsis decreased lethality in septic mice significantly and also suppressed the elevation of circulating TNF after sepsis. However, treatment with the same dose of IL-10 simultaneously or 6 h before induction of CLP had no effect on survival, and treatment with anti-TNF antibody after induction of CLP had no effect on the survival rate. These data suggest that cytokine modulation with IL-10 is a potential candidate for the treatment of sepsis and sepsis-related multiple organ failure.
Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression (2009)

High-throughput screening (HTS) assays used in drug discovery frequently use reporter enzymes such as firefly luciferase (FLuc) as indicators of target activity. An important caveat to consider, however, is that compounds can directly affect the reporter, leading to nonspecific but highly reproducible assay signal modulation. In rare cases, this activity appears counterintuitive; for example, some FLuc inhibitors, acting through posttranslational Fluc reporter stabilization, appear to activate gene expression. Previous efforts to characterize molecules that influence luciferase activity identified a subset of 3,5-diaryl-oxadiazole-containing compounds as FLuc inhibitors. Here, we evaluate a number of compounds with this structural motif for activity against FLuc. One such compound is PTC124 {3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid}, a molecule originally identified in a cell-based FLuc assay as having nonsense codon suppression activity [Welch EM, et al., Nature (2007) 447:87-91]. We find that the potency of FLuc inhibition for the tested compounds strictly correlates with their activity in a FLuc reporter cell-based nonsense codon assay, with PTC124 emerging as the most potent FLuc inhibitor (IC(50) = 7 +/- 1 nM). However, these compounds, including PTC124, fail to show nonsense codon suppression activity when Renilla reniformis luciferase (RLuc) is used as a reporter and are inactive against the RLuc enzyme. This suggests that the initial discovery of PTC124 may have been biased by its direct effect on the FLuc reporter, implicating firefly luciferase as a molecular target of PTC124. Our results demonstrate the value of understanding potential interactions between reporter enzymes and chemical compounds and emphasize the importance of implementing the appropriate control assays before interpreting HTS results.
A genetic system for studying the activity of a proteolytic enzyme. (1992)

We describe a genetic system for monitoring the activity of a specific proteolytic enzyme by taking advantage of the properties of the yeast transcriptional activator GAL4. The GAL4 protein contains two separable and functionally essential domains: the amino-terminal DNA binding domain and the carboxyl-terminal transcriptional activating domain. We constructed two hybrid proteins by inserting between the DNA binding domain and the activation domain of GAL4 either (i) a self-cleaving protease (3C protease of a picornavirus, coxsackievirus B3) or (ii) a mutant form of the protease that is unable to cleave. We show that, although the hybrid protein containing the mutant protease activates transcription of GAL1-lacZ reporter gene, the hybrid protein bearing the wild-type protease is proteolytically cleaved and fails to activate transcription. Our approach to monitor the proteolytic activity could be used to develop simple genetic systems to study other proteases.
Infrared Detection by Optical Mixing (1969)

A theoretical discussion is given of infrared detection systems employing an optically nonlinear crystal, a laser in the visible, and photomultiplier to detect the light produced at the sum or difference frequency. Three optical mixing systems are considered in detail and compared with direct detection: (a) cinnabar (HgS) in a single-pass optical system with the He–Ne 0.6328 μm cw laser, (b) the same crystal and laser with a ring resonator and narrow-band output filter, and (c) an ideal resonant system with a crystal as nonlinear as HgS but without absorption or double refraction. The noise output consisting of up-converted thermal noise and (in the case of the difference frequency) optical parametric noise is computed quantitatively. These systems have too small a quantum efficiency to compete with a heterodyne system employing an ir laser and a detector of high quantum efficiency such as a Ge:Cu-cooled photoconductor. The Ge:Cu detector has however a large dark noise compared to a good photomultiplier, and consequently optical mixing can surpass nonheterodyne direct detection if the required value of B≡(S/N)Δf is sufficiently small. The range of superiority of optical mixing over nonheterodyne direct detection extends high enough in B for Morse code for system (a) (if sum frequency is used), nearly high enough for a telephone channel for (b) and up to the television level for (c).
Optical Access Networks (2005)

Call for Papers: Optical Access Networks Guest Editors Jun Zheng, University of Ottawa Nirwan Ansari, New Jersey Institute of Technology Submission Deadline: 1 June 2005Background With the wide deployment of fiber-optic technology over the past two decades, we have witnessed a tremendous growth of bandwidth capacity in the backbone networks of today's telecommunications infrastructure. However, access networks, which cover the
Hypoxia and angiogenesis in rheumatoid arthritis (2005)

Despite the luxuriant vasculature associated with rheumatoid arthritis synovitis, the joint affected by rheumatoid arthritis is hypoxic. Repetitive cycles of hypoxia and reoxygenation together with oxidants produced by phagocytic cells promote chronic oxidative stress within the microenvironment of the affected joint, leading to the generation of reactive oxygen species with the potential to contribute to tissue damage.
Novel Polyanhydrides with Enhanced Thermal and Solubility Properties (2000)

A series of polyanhydrides based on o-, m-, and p-xylenes as derived from o- and p-hydroxybenzoic acids were synthesized by melt-condensation polymerization. Precursors, monomers, and polymers were characterized by NMR and IR spectroscopies, elemental and thermogravimetric analyses, and thermal transition temperatures. Polymers containing p-xylenes and p-hydroxybenzoic acids were relatively insoluble with high Tg's. In contrast, polymers containing o- and m-xylyl moieties based on o-hydroxybenzoic acids exhibit good solubilities and Tg's below 100 °C.
MA BE-SONOS: A Bandgap Engineered SONOS using Metal Gate and Al2O3 Blocking Layer to Overcome Erase Saturation (2007)

A bandgap engineered SONOS (BE-SONOS) (Lue et al., 2005) using Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> top blocking layer and metal gate (MA BE-SONOS) is proposed to provide very fast erase speed without erase saturation. Compared with MANOS (Shin et al., 2005) using a thick (4.5 nm) tunnel oxide, MA BE-SONOS shows dramatically faster erase speed, owing to the help of bandgap engineered ONO barrier that facilitates hole tunneling. Compared with BE-SONOS using P <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -poly gate and top oxide, MA BE-SONOS does not show any erase saturation, owing to the help of metal gate and AI <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> blocking layer, which greatly reduce gate injection during erase. Very large memory window (>7 V) can be achieved with excellent data retention. MA BE-SONOS overcomes the erase difficulty in SONOS-type devices, and is highly potential in the future flash memory technology.
Nature of the photonic band gap: some insights from a field analysis (1993)

To clarify the nature of photonic band gaps, a series of calculations on two-dimensional photonic crystals is undertaken. Systems that possess a large gap for one polarization and no gap for the other polarization are analyzed. Two features of a photonic crystal that give rise to a large photonic band gap for each polarization, i.e., connectivity and concentration of the dielectric material, are elucidated. The implications for making materials with large photonic band gaps in two and three dimensions are discussed.
Single carrier VSB digital television transmission, single-frequency networks, and repeater systems (1996)

Operation of single-carrier and multiple carrier systems under conditions of deliberately introduced echoes is examined. Problems in addition to intersymbol interference, which is specifically alleviated in multiple carrier (OFDM) systems with guard intervals, are examined. It is shown that the only advantage of coded orthogonal frequency division multiplexing (COFDM) is in the case of simple binary modulation of its individual carriers, which is not adequate to carry the data required for digital television.
Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder Cancer (2003)

As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.
The Herpes Simplex Virus gE-gI Complex Facilitates Cell-to-Cell Spread and Binds to Components of Cell Junctions (1998)

The herpes simplex virus (HSV) glycoprotein complex gE-gI mediates the spread of viruses between adjacent cells, and this property is especially evident for cells that form extensive cell junctions, e.g., epithelial cells, fibroblasts, and neurons. Mutants lacking gE or gI are not compromised in their ability to enter cells as extracellular viruses. Therefore, gE-gI functions specifically in the movement of virus across cell-cell contacts and, as such, provides a molecular handle on this poorly understood process. We expressed gE-gI in human epithelial cells by using replication-defective adenovirus (Ad) vectors. gE-gI accumulated at lateral surfaces of the epithelial cells, colocalizing with the adherens junction protein beta-catenin but was not found on either the apical or basal plasma membranes and did not colocalize with ZO-1, a component of tight junctions. In subconfluent monolayers, gE-gI was found at cell junctions but was absent from those lateral surfaces not in contact with another cell, as was the case for beta-catenin. Similar localization of gE-gI to cell junctions was observed in HSV-infected epithelial cells. By contrast, HSV glycoprotein gD, expressed using a recombinant Ad vectors, was found primarily along the apical surfaces of cells, with little or no protein found on the basal or lateral surfaces. Expression of gE-gI without other HSV polypeptides did not cause redistribution of either ZO-1 or beta-catenin or alter tight-junction functions. Together these results support a model in which gE-gI accumulates at sites of cell-cell contact by interacting with junctional components. We hypothesize that gE-gI mediates transfer of HSV across cell junctions by virtue of these interactions with cell junction components.
Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients. (1995)

To determine if partial T cell depletion and intensive post-transplant immunosuppression is effective for the prevention of graft-versus-host disease (GVHD) in pediatric recipients of HLA-non-identical marrow transplants, 10 children with leukemia received high-dose thiotepa, cyclophosphamide and total body irradiation followed by transplantation of CD3-depleted marrow from matched unrelated or one-antigen mismatched related adult donors. To maximize the number of stem cells infused, a large volume (1-1.51) of marrow was harvested from the donors. After immunopurging, the marrow infused contained a median of 3.7 x 10(6) CD34+ cells/kg, 1.4 x 10(6) CD3+ cells/kg, and 1.6 x 10(6) CD5+ cells/kg as assessed by flow cytometry. Cyclosporine, methylprednisolone and anti-CD4 ricin A chain immunotoxin (XZ-CD5) were used for prevention of GVHD post-transplant. All patients achieved an ANC > 0.5 x 10(9)/l. No patient developed capillary leak syndrome or renal failure from XZ-CD5. Five developed grade 2-4 acute GVHD, and all responded to treatment with steroids. Five of nine evaluable patients developed chronic GVHD. Two patients relapsed, but the most common cause of death was infection with or without chronic GVHD. Four patients survive 10+ to 27+ months post-transplant. XZ-CD5 is well-tolerated in T cell-depleted marrow transplant recipients. However, partial T cell depletion and intensive post-transplant immunosuppression did not prevent moderate acute GVHD or chronic GVHD. This may have been due to the high number of T cells infused with the marrow.
Female Sexual Satisfaction and Pharmaceutical Intervention: A Critical Review of the Drug Intervention Studies in Female Sexual Dysfunction (2006)

The investigation of FSD is an evolving area in that new definitions and a new model for female sexual functioning have been recently proposed. There is a need for experts in the field and regulating authorities to reach a consensus regarding appropriate inclusion and exclusion criteria for FSD trials and main outcome measures appropriate for the evaluation of drug interventions. This consensus should also determine which treatment effect is considered to be clinically relevant. Treatment efficacy and clinical relevance should be related to outcomes which are meaningful for affected women.
Coupled Homologous and Nonhomologous Repair of a Double-Strand Break Preserves Genomic Integrity in Mammalian Cells (2000)

DNA double-strand breaks (DSBs) may be caused by normal metabolic processes or exogenous DNA damaging agents and can promote chromosomal rearrangements, including translocations, deletions, or chromosome loss. In mammalian cells, both homologous recombination and nonhomologous end joining (NHEJ) are important DSB repair pathways for the maintenance of genomic stability. Using a mouse embryonic stem cell system, we previously demonstrated that a DSB in one chromosome can be repaired by recombination with a homologous sequence on a heterologous chromosome, without any evidence of genome rearrangements (C. Richardson, M. E. Moynahan, and M. Jasin, Genes Dev., 12:3831-3842, 1998). To determine if genomic integrity would be compromised if homology were constrained, we have now examined interchromosomal recombination between truncated but overlapping gene sequences. Despite these constraints, recombinants were readily recovered when a DSB was introduced into one of the sequences. The overwhelming majority of recombinants showed no evidence of chromosomal rearrangements. Instead, events were initiated by homologous invasion of one chromosome end and completed by NHEJ to the other chromosome end, which remained highly preserved throughout the process. Thus, genomic integrity was maintained by a coupling of homologous and nonhomologous repair pathways. Interestingly, the recombination frequency, although not the structure of the recombinant repair products, was sensitive to the relative orientation of the gene sequences on the interacting chromosomes.
Anti-HIV-1 Activity of Recombinant and Hybrid Species of Interferon-α (1992)

To identify candidate interferons (IFNs) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection and to investigate sequence-function relationships, the antiviral activities of nine species of recombinant IFN-alpha [IFN-alpha A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser116]IFN-alpha J1, IFN-alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)] were evaluated against HIV-1. MT-2 cells were exposed to various concentrations of each IFN and were then infected with HIV. Protective effect was determined by cell viability using a tetrazolium dye assay. Activity against vesicular stomatitis virus (VSV) was assessed on MDBK and WISH cells. The 50% inhibitory concentration against HIV was 37 +/- 14 pg/ml for IFN-alpha A, and ranged from 15 +/- 3 pg/ml for IFN-alpha J/C(Fnu4HI) to > 90,000 pg/ml for IFN-alpha D. In general, relative activity against HIV was similar to relative activity against VSV on WISH cells. IFN-alpha D was notable for its decreased activity on human cells. The observations suggest that it may be possible to produce IFNs-alpha with more favorable therapeutic indices than currently available IFNs. Furthermore, the anti-HIV activity of IFNs-alpha is not determined solely by their linear amino acid sequence.
Human liver sulphamate sulphohydrolase. Determinations of native protein and subunit Mr values and influence of substrate agylcone structure on catalytic properties (1986)

Human sulphamate sulphohydrolase was purified at least 20,000-fold to homogeneity from liver with a three-step four-column procedure, which consisted of a concanavalin A-Sepharose/Blue A agarose coupled step, and Bio-Gel HT step and then a CM-Sepharose step. The procedure was also used to purify enzyme from kidney and placenta. The subunit Mr of liver, kidney and placenta sulphamate sulphohydrolase was assessed to be 56,000 by using SDS/polacrylamide-gel electrophoresis. The native protein Mr of enzyme from all three tissue sources was assessed by gel-permeation chromatography to be approx. 120,000 on Sephacryl S-300 and 100,000 on Fractogel TSK. It is probable that the native enzyme results from dimerization of subunits. Kinetic parameters (km and kcat.) of human liver sulphamate sulphohydrolase were determined with a variety of substrates matching structural aspects of the physiological substrates in vivo, namely heparin and heparan sulphate. More structurally complex substrates, in which several aspects of the aglycone structure of the natural substrate were maintained, are turned over up to 372000 times faster than the monosaccharide substrate 2-sulphaminoglucosamine. Aglycone structures that influence substrate binding and/or enzyme activity were penultimate-residue C-6 carboxy and C-2 sulphate ester groups and a post-penultimate 2-sulphaminoglucosamine residue. The C-4 hydroxy group of the 2-sulphaminoglucosamine under enzymic attack is involved in binding of substrate to enzyme. The presence of C-6 sulphate ester on the non-reducing end 2-sulphaminoglucosamine stimulates sulphamate bond hydrolysis and substrate affinity if the adjacent monosaccharide residue is idose or 2-sulphoidose, but strongly inhibits hydrolysis if the adjacent monosaccharide residue is iduronic acid. Sulphamate sulphohydrolase is an exoenzyme, since activity toward internal sulphamate bonds was not detected. The effect of incubation pH on enzyme activity towards the variety of substrates evaluated was complex and dependent on substrate aglycone structure. The presence of aglycone C-2 sulphate ester and aglycone C-6 carboxy groups and C-6 sulphate ester groups on the 2-sulphaminoglucosamine residue under attack considerably affect the pH response. Structurally complex substrates had two pH optima. Incubation temperature and buffer ionic strength markedly influenced pH optima and enzyme activity. Cu2+ and SO4(2-)ions are potent inhibitors of enzyme activity.