gebhart/patrepeval huggingface dataset:
In vitro transposition of Tn552: a tool for DNA sequencing and mutagenesis (1999)

We have explored the potential of the Tn 552 in vitro transposition reaction as a genetic tool. The reaction is simple (requiring a single protein component), robust and efficient, readily producing insertions into several percent of target DNA. Most importantly, Tn 552 insertions in vitro appear to be essentially random. Extensive analyses indicate that the transposon exhibits no significant regional or sequence specificity for target DNA and leaves no discernible 'cold' spots devoid of insertions. The utility of the in vitro reaction for DNA sequencing was demonstrated with a cosmid containing the Mycobacterium smegmatis recBCD gene cluster. The nucleotide sequence of the entire operon was determined using 71 independent Tn 552 insertions, which generated over 13.5 kb of unique sequence and simultaneously provided a comprehensive collection of insertion mutants. The relatively short ends of Tn 552 make construction of novel transposons a simple process and we describe several useful derivatives. The data presented suggest that Tn 552 transposition is a valuable addition to the arsenal of tools available for molecular biology and genomics.
Regeneration of Mammalian Skeletal Muscle: Basic Mechanisms and Clinical Implications (2010)

Mammalian skeletal muscles can regenerate following injury and this response is mediated by a specific type of stem cell, the satellite cell. We review here the three main phases of muscle regeneration, including i) the initial inflammatory response and the dual role of macrophages as both scavengers involved in the phagocytosis of necrotic debris and promoters of myogenic differentiation, ii) the activation and differentiation of satellite cells and iii) the growth and remodeling of the regenerated muscle tissue. Nerve activity is required to support the growth of regenerated myofibers and the specification of muscle fiber types, in particular the activation of the slow gene program. We discuss the regeneration process in two different settings. Chronic degenerative diseases, such as muscular dystrophies, are characterized by repeated cycles of segmental necrosis and regeneration involving scattered myofibers. In these conditions the regenerative capacity of satellite cells becomes exhausted with time and fibrosis prevails. Acute traumatic injuries, such as strain injuries common in sport medicine, cause the rupture of large myofiber bundles leading to muscle regeneration and formation of scar tissue and new myotendinous junctions at the level of the rupture. Mechanical loading is essential for muscle regeneration, therefore, following initial immobilization to avoid the risk of reruptures, early remobilization is required to induce correct growth and orientation of regenerated myofibers. Finally, we discuss the causes of age-dependent decline in muscle regeneration potential and the possibility of boosting regeneration in aging muscle and in muscular dystrophies.
Reactivity profiles of broadly neutralizing anti-HIV-1 antibodies are distinct from those of pathogenic autoantibodies (2011)

The reactivity profiles of bNt anti-HIV-1 MAbs are fundamentally distinct from those of pathogenic autoAbs that arise from dysregulated tolerance mechanisms. This suggests that the limited polyreactivity observed for the bNt MAbs, and for HIV-1-Nt Abs in general, may arise through alternative mechanisms, such as extensive somatic mutation due to persistent antigen selection during chronic infection.
Concomitant Treatment with a 5-Lipoxygenase Inhibitor Improves the Anti-Inflammatory Effect of the Inhibition of Nitric Oxide Synthase during the Early Phase of Endotoxin-induced Uveitis in the Rabbit (1997)

Nitric oxide (NO) synthase inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), have been shown to attenuate endotoxin-induced uveitis (EIU) but they could increase leukocyte adhesion to the vascular endothelium. We hypothesize that a concomitant treatment with the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) in 50% dimethylsulfoxide (DMSO, a hydroxyl radical scavenger) could improve the anti-inflammatory activity of L-NAME. EIU was induced in albino rabbits by intravitreal injection of 100 ng lipopolysaccharide. Animals were treated with multiple intraperitoneal injections of 50% DMSO in phosphate-buffered saline (PBS), NDGA (10 mg/kg) in 50% DMSO, L-NAME (50 mg/ kg) in PBS, or the combination NDGA+L-NAME. Uveitis was assessed by slit lamp examination, protein levels in aqueous humor, and myeloperoxidase (MPO) activity in the iris/ciliary body 6 h after induction. Nitrite, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), platelet-activating factor (PAF) and interleukin-1 beta (IL-1 beta) levels in aqueous humor were also determined. NDGA or L-NAME alone did not show a significant reduction of uveitis intensity, although a significant decrease in MPO or in proteins was found, respectively. The combination NDGA+L-NAME significantly reduced the uveitis intensity, MPO in the iris/ciliary body, and the levels of nitrites, LTB4, PGE2, and PAF in aqueous humor. IL-1 beta levels were lower than the detection limit of the radioimmunoassay in all treatment groups. We conclude that concomitant treatment with NDGA in DMSO improves the anti-inflammatory activity of L-NAME during the early phase of EIU, suggesting that the inhibition of NO synthesis could enhance leukocyte infiltration and the release of oxygen free radicals.
Aminophylline Therapy for Acute Bronchospastic Disease in the Emergency Room (1991)

Aminophylline, in doses producing levels just below the commonly accepted therapeutic range, appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. This finding, if confirmed in larger studies, may represent a substantial cost savings.
Suppression of experimental autoimmune diseases and prolongation of allograft survival by treatment of animals with low doses of heparins. (1989)

The ability of activated T lymphocytes to penetrate the extracellular matrix and migrate to target tissues was found to be related to expression of a heparanase enzyme (Naparstek, Y., I. R. Cohen, Z. Fuks, and I. Vlodavsky. 1984. Nature (Lond.). 310:241-243; Savion, N., Z. Fuks, and I. Vlodavsky. 1984. J. Cell. Physiol. 118:169-176; Fridman, R., O. Lider, Y. Naparstek, Z. Fuks, I. Vlodavsky, and I. R. Cohen. 1987. J. Cell. Physiol. 130:85-92; Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We found previously that heparin molecules inhibited expression of T lymphocyte heparanase activity in vitro and in vivo, and administration of a low dose of heparin in mice inhibited lymphocyte traffic and delayed-type hypersensitivity reactions (Lider, O., J. Mekori, I. Vlodavsky, E. Baharav, Y. Naparstek, and I. R. Cohen, manuscript submitted for publication). We now report that treatment with commercial or chemically modified heparins at relatively low doses once daily (5 micrograms for mice and 20 micrograms for rats) led to inhibition of allograft rejection and the experimental autoimmune diseases adjuvant arthritis and experimental autoimmune encephalomyelitis. Higher doses of the heparins were less effective. The ability of chemically modified heparins to inhibit these immune reactions was associated with their ability to inhibit expression of T lymphocyte heparanase. There was no relationship to anticoagulant activity. Thus heparins devoid of anticoagulant activity can be effective in regulating immune reactions when used at appropriate doses.
Diagnosis of Schistosomiasis by Reagent Strip Test for Detection of Circulating Cathodic Antigen (2004)

A newly developed reagent strip assay for the diagnosis of schistosomiasis based on parasite antigen detection in urine of infected individuals was evaluated. The test uses the principle of lateral flow through a nitrocellulose strip of the sample mixed with a colloidal carbon conjugate of a monoclonal antibody specific for Schistosoma circulating cathodic antigen (CCA). The strip assay to diagnose a group of highly infected schoolchildren in Mwanza, Tanzania, demonstrated a high sensitivity and association with the intensity of infection as measured both by egg counts, and by circulating anodic antigen and CCA levels determined by enzyme-linked immunosorbent assay. A specificity of ca. 90% was shown in a group of schistosome-negative schoolchildren from Tarime, Tanzania, an area where schistosomiasis is not endemic. The test is easy to perform and requires no technical equipment or special training. The stability of the strips and the conjugate in the dry format lasts for at least 3 months at ambient temperature in sealed packages, making it suitable for transport and use in areas where schistosomiasis is endemic. This assay can easily be developed to an end-user format.
The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2) activation (2015)

Oxidative stress-induced retinal pigment epithelial (RPE) cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD). Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200μM H2O2 for 6h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI) double staining and Hoechst 33342 fluorescent staining. Reduced (GSH) and oxidized glutathione (GSSG) were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100nM) of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.
Shiga Toxin 1 Triggers a Ribotoxic Stress Response Leading to p38 and JNK Activation and Induction of Apoptosis in Intestinal Epithelial Cells (2003)

Shiga toxins made by Shiga toxin-producing Escherichia coli (STEC) are associated with hemolytic uremic syndrome. Shiga toxins (Stxs) may access the host systemic circulation by absorption across the intestinal epithelium. The effects of Stxs on this cell layer are not completely understood, although animal models of STEC infection suggest that, in the gut, Stxs may participate in both immune activation and apoptosis. Stxs have one enzymatically active A subunit associated with five identical B subunits. The A subunit inactivates ribosomes by cleaving a specific adenine from the 28S rRNA. We have previously shown that Stxs can induce multiple C-X-C chemokines in intestinal epithelial cells in vitro, including interleukin-8 (IL-8), and that Stx-induced IL-8 expression is linked to induction of c-Jun mRNA and p38 mitogen-activated protein (MAP) kinase pathway activity. We now report Stx1 induction of both primary response genes c-jun and c-fos and activation of the stress-activated protein kinases, JNK/SAPK and p38, in the intestinal epithelial cell line HCT-8. By 1 h of exposure to Stx1, mRNAs for c-jun and c-fos are induced, and both JNK and p38 are activated; activation of both kinases persisted up to 24 h. Stx1 enzymatic activity was required for kinase activation; a catalytically defective mutant toxin did not activate either. Stx1 treatment of HCT-8 cells resulted in cell death that was associated with caspase 3 cleavage and internucleosomal DNA fragmentation; this cytotoxicity also required Stx1 enzymatic activity. Blocking Stx1-induced p38 and JNK activation with the inhibitor SB202190 prevented cell death and diminished Stx1-associated caspase 3 cleavage. In summary, these data link the Stx1-induced ribotoxic stress response with both chemokine expression and apoptosis in the intestinal epithelial cell line HCT-8 and suggest that blocking host cell MAP kinases may prevent these Stx-associated events.
Inhibition of Bone Resorption by Pamidronate Cannot Restore Normal Gain in Cortical Bone Mass and Strength in Tail-Suspended Rapidly Growing Rats (1997)

To clarify how the changes in bone formation and resorption affect bone volume and strength after mechanical unloading, the effect of inhibition of bone resorption by a potent bisphosphonate, pamidronate, on bone mineral density (BMD), histology, and strength of hind limb bones was examined using tail-suspended growing rats. Tail suspension for 14 days reduced the gain in the BMD of the femur at both the metaphysis rich in trabecular bone and the diaphysis rich in cortical bone. Treatment with pamidronate increased the total BMD as well as that of the metaphysis of the femur but had almost no effect on the BMD of the diaphysis in both control and tail-suspended rats. Histological examinations revealed that 14-day tail suspension caused a loss of secondary cancellous bone with a reduction in the trabecular number and thickness in comparison with control rats. In the femoral diaphysis, the diameter and cortical bone thickness increased to a lesser degree in tail-suspended rats when compared with rats without tail suspension, and a marked reduction in bone formation and the layers of alkaline phosphatase-positive cells was observed at the periosteal side. Pamidronate treatment increased secondary cancellous bone but could not restore normal growth-induced periosteal bone apposition and bone strength. Because the material strength of the femoral diaphysis at the tissue level was not affected by pamidronate treatment, the inability of pamidronate to prevent the reduction in physical strength of the femoral diaphysis does not appear to be due to a change in the quality of newly formed bone. These results demonstrate that tail suspension reduces the growth-induced periosteal modelling drift and that the antiresorptive agent pamidronate is unable to restore normal periosteal bone apposition.
Diabetic Hyperglycemia: Link to Impaired Glucose Transport in Pancreatic β Cells (1991)

Glucose uptake into pancreatic beta cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia. In both autoimmune and nonautoimmune diabetes, this glucose transport is reduced as a consequence of down-regulation of the normal beta-cell transporter. In autoimmune diabetes, circulating immunoglobulins can further impair this glucose transport by inhibiting functionally intact transporters. Insights into mechanisms of the unresponsiveness of beta cells to hyperglycemia may improve the management and prevention of diabetes.
Preparation and Stabilization of Heparin/Gelatin Complex Coacervate Microcapsules (1997)

The aims of this study are to optimize conditions for the preparation, stabilization, and harvesting of heparin/gelatin microcapsules prepared by complex coacervation. Microelectrophoresis and dry coacervate weight were used to determine the optimum conditions of pH and ionic strength for maximum heparin/gelatin coacervate yield. Heparin/gelatin microcapsules were formed by complex coacervation in the presence and absence of poly(1-vinyl-2-pyrrolidone) (PVP), which was used as a stabilizer. The microcapsules were collected using a spray-drying technique. Microcapsule particle size was analyzed using an AccuSizer optical sizer. Optimized conditions for maximum coacervate yield were pH 2.6, ionic strength 10 mM, and a 1:2 heparin/gelatin A ratio. PVP stabilized the heparin/gelatin coacervate droplets and reduced droplet aggregation during spray-drying. The mean particle diameter of the spray-dried coacervate droplets was lower in the presence of PVP and was unaffected by PVP concentration (in the range 0.5-2.0% w/w). Heparin/gelatin microcapsules, prepared under conditions optimized for maximum coacervate yield, were stabilized without the use of chemical cross-linking agents. Stabilization was achieved by a combination of the addition of PVP and spray-drying.
Identification of the secretory vesicle membrane binding region of chromogranin B1 (1997)

In the past a synthetic peptide representing the conserved near N‐terminal region of chromogranin B (CGB) (residues 17–36) has been shown to interact with the vesicle membrane. Hence, it was necessary to confirm this observation with CGB deletion proteins. In order to address this need and to confirm the published sequence of CGB, we cloned a CGB gene and produced various CGB deletion proteins. The recombinant CGB protein lacking the first 15 (rCGB 16–626) or 16 amino acid residues (rCGB 17–626) bound to the vesicle membrane as well as the full‐length CGB. However, rCGB 49–626, lacking the conserved near N‐terminal region, failed to interact with the vesicle membrane, indicating an anchor role for the conserved near the N‐terminal region.
Niclosamide repurposed for the treatment of inflammatory airway disease (2019)

Inflammatory airway diseases, such as asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD), are characterized by mucus hypersecretion and airway plugging. In both CF and asthma, enhanced expression of the Ca2+-activated Cl- channel TMEM16A is detected in mucus-producing club/goblet cells and airway smooth muscle. TMEM16A contributes to mucus hypersecretion and bronchoconstriction, which are both inhibited by blockers of TMEM16A, such as niflumic acid. Here we demonstrate that the FDA-approved drug niclosamide, a potent inhibitor of TMEM16A identified by high-throughput screening, is an inhibitor of both TMEM16A and TMEM16F. In asthmatic mice, niclosamide reduced mucus production and secretion, as well as bronchoconstriction, and showed additional antiinflammatory effects. Using transgenic asthmatic mice, we found evidence that TMEM16A and TMEM16F are required for normal mucus production/secretion, which may be due to their effects on intracellular Ca2+ signaling. TMEM16A and TMEM16F support exocytic release of mucus and inflammatory mediators, both of which are blocked by niclosamide. Thus, inhibition of mucus and cytokine release, bronchorelaxation, and reported antibacterial effects make niclosamide a potentially suitable drug for the treatment of inflammatory airway diseases, such as CF, asthma, and COPD.
Across-site patterns of modulation detection: Relation to speech recognition (2012)

The aim of this study was to identify across-site patterns of modulation detection thresholds (MDTs) in subjects with cochlear implants and to determine if removal of sites with the poorest MDTs from speech processor programs would result in improved speech recognition. Five hundred millisecond trains of symmetric-biphasic pulses were modulated sinusoidally at 10 Hz and presented at a rate of 900 pps using monopolar stimulation. Subjects were asked to discriminate a modulated pulse train from an unmodulated pulse train for all electrodes in quiet and in the presence of an interleaved unmodulated masker presented on the adjacent site. Across-site patterns of masked MDTs were then used to construct two 10-channel MAPs such that one MAP consisted of sites with the best masked MDTs and the other MAP consisted of sites with the worst masked MDTs. Subjects' speech recognition skills were compared when they used these two different MAPs. Results showed that MDTs were variable across sites and were elevated in the presence of a masker by various amounts across sites. Better speech recognition was observed when the processor MAP consisted of sites with best masked MDTs, suggesting that temporal modulation sensitivity has important contributions to speech recognition with a cochlear implant.
Cognitive changes after cerebrospinal fluid shunting in young adults with spina bifida and assumed arrested hydrocephalus (2000)

Young adults with spina bifida and suspected non-functioning shunt or non-shunted ventriculomegaly should be carefully monitored to identify those who could benefit from shunting.
Synthesis of Some Sulfur Bridged Pyrimidines, Pyrazoles and Imidazoles (1997)

The preparation of some sulfur bridged substituted pyrimidines, pyrazoles, and imidazoles is reported in this communication.
Fast authentication methods for handovers between IEEE 802.11 wireless LANs (2004)

Improving authentication delay is a key issue for achieving seamless handovers across networks and domains. This paper presents an overview of fast authentication methods when roaming within or across IEEE 802.11 Wireless-LANs. Besides this overview, the paper analyses the applicability of IEEE 802.11f and Seamoby solutions to enable fast authentication for inter-domain handovers. The paper proposes a number of possible changes to these solutions (typically in terms of network architectures and/or required trust relationships) for inter-domain operation. In addition, the paper identifies the crucial research issues therein. Possible solutions and directions for future research include: update to security infrastructure, inter-layer communication and discovery of appropriate networks.
Diversity through coded cooperation (2006)

Motivated by the recent works on the relay channel and cooperative diversity, this letter introduces coded cooperation, where cooperation is achieved through channel coding methods instead of a direct relay or repetition. Each codeword is partitioned into two subsets that are transmitted from the user's and partner's antennas, respectively. Coded cooperation achieves impressive gains compared to a non-cooperative system while maintaining the same information rate, transmit power, and bandwidth. We develop bounds on BER and FER and illustrate the advantage of coded cooperation under a number of different scenarios.
Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs. (1977)

Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.