gebhart/patrepeval huggingface dataset:
Targeting RNA Foci in iPSC-Derived Motor Neurons from ALS Patients with a C9ORF72 Repeat Expansion (2013)

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. We report a cellular model of C9-ALS with motor neurons differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying the C9ORF72 repeat expansion. No significant loss of C9ORF72 expression was observed, and knockdown of the transcript was not toxic to cultured human motor neurons. Transcription of the repeat was increased, leading to accumulation of GGGGCC repeat-containing RNA foci selectively in C9-ALS iPSC-derived motor neurons. Repeat-containing RNA foci colocalized with hnRNPA1 and Pur-α, suggesting that they may be able to alter RNA metabolism. C9-ALS motor neurons showed altered expression of genes involved in membrane excitability including DPP6, and demonstrated a diminished capacity to fire continuous spikes upon depolarization compared to control motor neurons. Antisense oligonucleotides targeting the C9ORF72 transcript suppressed RNA foci formation and reversed gene expression alterations in C9-ALS motor neurons. These data show that patient-derived motor neurons can be used to delineate pathogenic events in ALS.
Glucagon secretory response to hypoglycaemia, adrenaline and carbachol in streptozotocindiabetic rats (1995)

Glucagon response to insulin-induced hypoglycaemia is impared in diabetes, but the mechanism is not established. Pancreatic A cell hyporesponsiveness to adrenergic or cholinergic stimulation could contribute to the impairment. We therefore compared the plasma glucagon responses to intravenous infusion of adrenaline (1200 ng kg(-1) min(-1) for 20 min) or to intravenous injection of the cholinergic agonist carbachol (50 micrograms kg(-1)) in chloral hydrate-anaesthetized rats made diabetic with the use of streptozotocin (80 mg kg(-1) subcutaneously) 6 weeks before and in anaesthetized control rats. Insulin was infused intravenously to reduce plasma glucose levels to below 1.8 mmol L(-1). As expected, the plasma glucagon response was reduced by approximately 45% in streptozotocin-diabetic rats compared with controls (P = 0.045). During adrenaline infusion, plasma glucagon levels increased by 277 +/- 92 pg mL(-1) in controls (P = 0.009) and by 570 +/- 137 pg mL(-1) in the diabetic rats (P = 0.002). Thus, the plasma glucagon response to adrenaline was approximately doubled in the diabetic rats (P = 0.045). Following carbachol injection, plasma glucagon levels were raised by 1211 +/- 208 pg mL(-1) (P < 0.001) in controls but only by 555 +/- 242 pg mL(-1) in the diabetic rats (P = 0.049). Thus, the plasma glucagon response to carbachol was impared by approximately 58% in the diabetic rats (P = 0.028). We conclude that carbachol-stimulated glucagon secretion is impared concomitantly with the impared glucagon response to hypoglycaemia in streptozotocin-diabetic rats, whereas adrenaline-induced glucagon secretion is exaggerated. We suggest that a reduced pancreatic A cell responsiveness to cholinergic stimulation could contribute to the impairment of the glucagon response to insulin-induced hypoglycaemia in diabetes.
Treatment of rheumatoid arthritis with L-histidine: a randomized, placebo-controlled, double-blind trial. (1977)

A randomized cooperative double-blind trial of oral L-histidine for the treatment of rheumatoid arthritis was carried out. Patients were treated with either L-histidine 4.5 g daily, or placebo, for 30 weeks. None of the clinical measurements showed an advantage of histidine over placebo. A small decrease in rheumatoid factor titer and a small increase in hematocrit were found only in the histidine group. There was suggestive evidence of a beneficial effect of histidine in patients with more active and prolonged disease, based upon subjective doubld-blind evaluations by physicians and patients. No adverse effects of histidine therapy were noted. Histidine cannot be advocated as a therapeutic agent in rheumatoid arthritis, but further studies in certain groups of patients seem justified.
NTS/NTR1 co-expression enhances epithelial-to-mesenchymal transition and promotes tumor metastasis by activating the Wnt/β-catenin signaling pathway in hepatocellular carcinoma (2016)

Neurotensin (NTS) is a neuropeptide distributed in central nervous and digestive systems. In this study, the significant association between ectopic NTS expression and tumor invasion was confirmed in hepatocellular carcinoma (HCC). In primary HCC tissues, the NTS and neurotensin receptor 1 (NTR1) co-expression (NTS+NTR1+) is a poor prognostic factor correlated with aggressive biological behaviors and poor clinical prognosis. Enhanced epithelial-to-mesenchymal transition (EMT) features, including decreased E-cadherin, increased β-catenin translocation and N-cadherin expression, were identified in NTS+NTR1+ HCC tissues. Varied NTS-responsible HCC cell lines were established using NTR1 genetically modified Hep3B and HepG2 cells which were used to elucidate the molecular mechanisms regulating NTS-induced EMT and tumor invasion in vitro. Results revealed that inducing exogenous NTS stimulation and enhancing NTR1 expression promoted tumor invasion rather than proliferation by accelerating EMT in HCC cells. The NTS-induced EMT was correlated with the remarkable increase in Wnt1, Wnt3, Wnt5, Axin, and p-GSK3β expression and was significantly reversed by blocking the NTS signaling via the NTR1 antagonist SR48692 or by inhibiting the activation of the Wnt/β-catenin pathway via specific inhibitors, such as TSW119 and DKK-1. SR48692 also inhibited the metastases of NTR1-overexpressing HCC xenografts in the lungs in vivo. This finding implied that NTS may be an important stimulus to promote HCC invasion and metastasis both in vitro and in vivo, and NTS signaling enhanced the tumor EMT and invasion potentials by activating the canonical Wnt/β-catenin signaling pathway. Therefore, NTS may be a valuable therapeutic target to prevent tumor progression in HCC.
Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres (1998)

These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.
Double-blind trial of botulinum A toxin for the treatment of focal hyperhidrosis of the palms. (1997)

We performed a randomized double-blind study within-group comparison in 11 patients to study the effect of subcutaneous injections of botulinum A toxin in focal hyperhidrosis of the palms. A total dose of 120 mU (mouse units) of botulinum A toxin (Dysport) was injected into six different sites on one palm, whereas the other was injected with sterile saline. Objective quantification of sweat production was performed using digitized ninhydrin-stained sheets. Three weeks after treatment, the mean reduction of sweat production in the botulinum A toxin-treated palms was 26% (P < 0.001), after 8 weeks 26% (P = 0.002) and after 13 weeks 31% (P < 0.001). Subjective assessment of sweat production by the patients using a visual analogue scale showed a 38% improvement in the botulinum A toxin-treated palms at 3 weeks (P = 0.002), 40% at 8 weeks (P = 0.002) and 38% at 13 weeks (P = 0.002). Neither the objective measurement nor the subjective rating showed a statistically significant reduction of sweating in the placebo-treated palms. Three patients reported reversible minor weakness of powerful handgrip after injection at the toxin-treated site, lasting between 2 and 5 weeks.
Assembly of Tat‐dependent [NiFe] hydrogenases: identification of precursor‐binding accessory proteins (2003)

The Escherichia coli twin-arginine translocation (Tat) system serves to export fully folded protein substrates across the bacterial cytoplasmic membrane. Respiratory [NiFe] hydrogenases are synthesised as precursors with twin-arginine signal peptides and transported as large, cofactor-containing, multi-subunit complexes by the Tat system. Cofactor insertion and assembly of [NiFe] hydrogenases requires coordination of networks of accessory proteins. In this work we utilise a bacterial two-hybrid assay to demonstrate protein-protein interactions between the uncharacterised chaperones HyaE and HybE with Tat signal peptide-bearing hydrogenase precursors. It is proposed that the chaperones act at a 'proofreading' stage in hydrogenase assembly and police the protein transport pathway preventing premature targeting of Tat-dependent hydrogenases.
Two Randomized Trials of Linaclotide for Chronic Constipation (2011)

In these two 12-week trials, linaclotide significantly reduced bowel and abdominal symptoms in patients with chronic constipation. Additional studies are needed to evaluate the potential long-term risks and benefits of linaclotide in chronic constipation. (Funded by Ironwood Pharmaceuticals and Forest Research Institute; ClinicalTrials.gov numbers, NCT00765882 and NCT00730015.).
The Yersinia pseudotuberculosis adhesin YadA mediates intimate bacterial attachment to and entry into HEp-2 cells (1993)

We characterized a bacterium-host cell interaction that is mediated by the Yersinia adhesin YadA. Derivatives of the virulence plasmid pIB1 harboring mutations in yadA, yopE, or yopH or in a low-calcium-response regulatory locus were introduced into a Yersinia pseudotuberculosis YPIII strain defective for Inv. The mutant strains were tested for the capacity to attach to and enter HEp-2 cells and express the cytotoxic activities of YopE and YopH. As previously shown, expression of YadA was necessary for bacterial attachment and Yop activity in the absence of Inv (R. Rosqvist, A. Forsberg, M. Rimpilainen, T. Bergman, and H. Wolf-Watz, Mol. Microbiol. 4:657-667, 1990). In addition, bacterial entry into HEp-2 cells occurred efficiently when YadA was expressed in the absence of YopE and YopH. These results demonstrated that YadA mediates intimate attachment of Y. pseudotuberculosis to HEp-2 cells and that phagocytic uptake of bacteria by this pathway is inhibited by the synergistic activities of YopH and YopE. A role for beta 1 integrins as host cell receptors for this bacterial attachment and entry mechanism was supported by HEp-2 cell adhesion and monoclonal antibody neutralization studies.
Performance and Reliability Improvements for Heavy Duty Gas Turbines (1987)

Many significant advances in technology have been applied to new unit production in the past 15 years. These technology improvements can be applied to field units to achieve increased performance, life, and/or reliability. Several types of improvement are now available for compressors, combustion systems, hot gas path turbine parts, and turbine controls. This paper provides a summary of performance improvements available for General Electric gas turbines MS3002, MS5001, MS5002, MS6001, MS7001, and MS9001 and tabulations of performance for each improvement. Also provided are detailed descriptions of control modernization designs available for improving the operating reliability of field units.
Isolation and Characterization of Novel Oligosaccharides Related to Ziracin (2002)

Five novel oligosaccharide antibiotics, Sch 58769 (1), Sch 58771 (2), Sch 58773 (3), Sch 58775 (4), and Sch 58777 (5), were isolated from the fermentation broth of Micromonospora carbonacea var africana. Their structures were determined by spectroscopic methods, including MS and (1)H and (13)C NMR experiments. A comparison of the obtained data with that for Ziracin (Sch 27899) revealed that these oligosaccharides belong to the same everninomicin family of compounds. Ziracin demonstrates potent activity against Gram-positive bacteria both in vitro and in vivo including multiply resistant strains of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci faecalis.
Envisor: Online Environment Map Construction for Mixed Reality (2008)

One of the main goals of anywhere augmentation is the development of automatic algorithms for scene acquisition in augmented reality systems. In this paper, we present Envisor, a system for online construction of environment maps in new locations. To accomplish this, Envisor uses vision-based frame to frame and landmark orientation tracking for long-term, drift-free registration. For additional robustness, a gyroscope/compass orientation unit can optionally be used for hybrid tracking. The tracked video is then projected into a cubemap frame by frame. Feedback is presented to the user to help avoid gaps in the cubemap, while any remaining gaps are filled by texture diffusion. The resulting environment map can be used for a variety of applications, including shading of virtual geometry and remote presence.
c-myc reverses neu-induced transformed morphology by transcriptional repression. (1991)

Amplification or overexpression or both of either the c-myc or the human neu (C-erbB-2) gene are common events in many primary human tumors. Coamplification or overexpression or both of both genes have been reported in some breast cancers. The possibility of cooperation between the c-myc and the normal rat neu (c-neu) genes in transforming cells was examined. Surprisingly, the expression of c-myc in B104-1-1 cells, and activated rat neu oncogene (neu*)-transformed NIH 3T3 line, resulted in morphologic reversion. This reversion was found to be a consequence of a transcription-repressive action of c-myc on the neu gene via a 140-bp fragment on the neu gene promoter. The effective concentration of a positive factor(s) interacting with this fragment seemed to be lowered by the expression of c-myc. Our findings lend support to arguments concerning the long-suspected function of c-myc as a transcriptional modulator. They also imply that an oncogene such as c-myc, or possibly the rapidly explored class that encodes transcription factors, under certain conditions may act to reverse a transformed phenotype that is induced by another oncogene instead of contributing positively towards the transformation process. Therefore, the activity of an oncogene may depend on the environment in which it is expressed. In addition, we may have identified the neu gene as a cellular target gene of negative regulation by c-myc.
MODES OF GENE TRANSFER AND RECOMBINATION IN BACTERIA (1978)

INTRODUCTION . MODES OF GENETIC RECOMBINATION . MODES OF GENE TRANSFER .. Transformation , ........ ... .. ... ... ... .. Phage Conversion . Transduction: Specialized .. Transduction: Generalized . Phage-Associated Gene Transfer . Capsduction .
On the link between foam coarsening and surface rheology: why hydrophobins are so different (2010)

Why are hydrophobins so different? To understand this, here we compare the stability of foams made with hydrophobin HFBII, Quillaja saponin, β-lactoglobulin or β-casein. Our experimental design eliminates the effects of coalescence and creaming, allowing us to study Ostwald ripening primarily. We observe that in HFBII foams, disproportionation is effectively stopped and the air bubbles size remains practically constant over the time of the experiment. We explain this with the large differences in surface rheological properties of the adsorbed layers, which were studied using small and large deformation surface dilational and shear rheology experiments. At low surface coverage we have mapped the system behaviour to the equivalent 2D polymer network having similar dilational modulus vs. surface pressure dependence, allowing us to introduce an equivalent molecular “hardness”. This comparison indicates that even at low surface coverage, HFBII molecules behave as harder entity at the interface, when compared to other systems. We find similar behaviour at high surface coverage, where HFBII layers can form microscopic wrinkles at the interface. At large surface deformation the HFBII dilational modulus increases nearly monotonically, over a much larger range of surface pressures, and much higher moduli are reached compared to the other three systems. These observations correlate well with the observed difference in the foam behaviour.
General Acid-Base Catalysis in the Mechanism of a Hepatitis Delta Virus Ribozyme (2000)

Many protein enzymes use general acid-base catalysis as a way to increase reaction rates. The amino acid histidine is optimized for this function because it has a pK(a) (where K(a) is the acid dissociation constant) near physiological pH. The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond. Reactivity-pH profiles in monovalent or divalent cations, as well as distance to the leaving-group oxygen, implicate cytosine 75 (C75) of the ribozyme as the general acid and ribozyme-bound hydrated metal hydroxide as the general base in the self-cleavage reaction. Moreover, C75 has a pK(a) perturbed to neutrality, making it "histidine-like." Anticooperative interaction is observed between protonated C75 and a metal ion, which serves to modulate the pK(a) of C75. General acid-base catalysis expands the catalytic repertoire of RNA and may provide improved rate acceleration.
The Molecular Effects of Acrolein (2000)

Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which humans are exposed in a variety of environmental situations, particularly as a component of smoke. In addition, as a metabolite of cyclophosphamide, acrolein is a major factor in the toxicity and perhaps the therapeutic activity of this important anticancer agent. The exposures to acrolein that are attained in vivo in most situations are quite low and the effects may differ from those seen at acutely toxic doses. At low doses, acrolein inhibits cell proliferation without causing cell death and may enhance apoptosis from secondary toxins, while at higher doses oncosis ensues. Although the acute toxicology of acrolein has been extensively investigated, both in animals and cultured cells, little information exists on the molecular effects of this reactive aldehyde. It is possible that the acrolein-mediated decrease in cell proliferation is caused by effecting changes in the expression of one or more growth- or stress-related genes or transcription factors secondary to a reduction in glutathione (GSH), which is rapidly depleted following acrolein treatment. It is apparent that the activation of the transcription factors nuclear factor kappa B (NF-kappa B) and activator protein 1 (AP-1) can be inhibited by acrolein. The purpose of this review is to assess the literature currently available on the molecular effects of acrolein, to discuss the relationship between effects on glutathione with those on various genes, and to present some new data showing that acrolein actively stimulates genes associated with the electrophile response element.
Direct Conductance Measurement of Single DNA Molecules in Aqueous Solution (2004)

We have studied electron transport in DNA duplexes, covalently bonded to two electrodes in aqueous buffer solutions, by repeatedly forming a large number of DNA junctions. The histogram of conductances reveals peaks at integer multiples of a fundamental value, which is used to identify with the conductance of a single DNA molecule. The measured conductance depends on the DNA sequence and length. For (GC)n sequences, the conductance is inversely proportional to the length (greater than eight base pairs). When inserting (A:T)m into GC-rich domains, it decreases exponentially with the length of A:T base pairs (m) with a decay constant of 0.43 Å-1. This work provides an unambiguous determination of single DNA conductance and demonstrates different conduction mechanisms for different sequences.
A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C (2012)

This strategy can be efficiently used and is cost effective for the generation of diverse recombinant antibodies. This is the first study to generate anti-V3 scFvs against HIV-1 Clade C.
Proliferating Resident Microglia after Focal Cerebral Ischaemia in Mice (2007)

Cerebral ischaemia usually results in the rapid death of neurons within the immediate territory of the affected artery. Neuronal loss is accompanied by a sequence of events, including brain oedema, blood-brain barrier (BBB) breakdown, and neuroinflammation, all of which contribute to further neuronal death. Although the role of macrophages and mononuclear phagocytes in the expansion of ischaemic injury has been widely studied, the relative contribution of these cells, either of exogenous or intrinsic central nervous system (CNS) origin is still not entirely clear. The purpose of this study, therefore, was to use different durations of transient middle cerebral artery occlusion (tMCAo) in the mouse to investigate fully post-occlusion BBB permeability and cellular changes in the brain during the 72 h post-MCAo period. This was achieved using in vivo magnetic resonance imaging (MRI) and cell labelling techniques. Our results show that BBB breakdown and formation of the primary ischaemic damage after tMCAo is not associated with significant infiltration of neutrophils, although more are observed with longer periods of MCAo. In addition, we observe very few infiltrating exogenous macrophages over a 72 h period after 30 or 60 mins of occlusion, instead a profound increase in proliferating resident microglia cells was observed. Interestingly, the more severe injury associated with 60 mins of MCAo leads to a markedly reduced proliferation of resident microglial cells, suggesting that these cells may play a protective function, possibly through phagocytosis of infiltrating neutrophils. These data further support possible beneficial actions of microglial cells in the injured brain.
Antimicrobial Silver/Sodium Carboxymethyl Cotton Dressings for Burn Wounds (2005)

Antimicrobial Ag/Na carboxymethyl cotton burn dressings are developed by partial cation exchange of sodium by silver from sodium carboxymethyl cotton gauze/nonwovens through treatment with silver nitrate in an 85/15 ethanol/water medium. The ethanol/water medium is necessary to preserve the fibrous form of carboxymethyl gauze/nonwovens with a degree of substitution of 0.3 to 0.4. From the behavior of antimicrobial release and the suppression of bacterial and fungal proliferation, it is apparent that the dressings containing the silver antimicrobial agent will protect wound surfaces from microbial invasion and effectively suppress bacterial proliferation. Antimicrobial evaluations of Ag/Na carboxymethyl cotton at North American Science Associates and the Southern Regional Research Center are positive. Additionally, the results show that an enhanced burn treatment is possible using a highly moisture retentive sodium carboxymethyl gauze instead of conventional gauze now used with silver nitrate. The carboxymethyl gauze’s capacity to hold a large amount of antimicrobial solution creates the possibility for better antimicrobial treatment. The retention of a greater amount of silver nitrate solution on the dressing will require less replenishment of solution on dressings on patients, which will reduce nursing time.