gebhart/patrepeval huggingface dataset:
Cleavage at the 586 Amino Acid Caspase-6 Site in Mutant huntingtin Influences Caspase-6 ActivationIn Vivo (2010)

Caspase cleavage of huntingtin (htt) and nuclear htt accumulation represent early neuropathological changes in brains of patients with Huntington's disease (HD). However, the relationship between caspase cleavage of htt and caspase activation patterns in the pathogenesis of HD remains poorly understood. The lack of a phenotype in YAC mice expressing caspase-6-resistant (C6R) mutant htt (mhtt) highlights proteolysis of htt at the 586 aa caspase-6 (casp6) site as a key mechanism in the pathology of HD. The goal of this study was to investigate how proteolysis of htt at residue 586 plays a role in the pathogenesis of HD and determine whether inhibiting casp6 cleavage of mhtt alters cell-death pathways in vivo. Here we demonstrate that activation of casp6, and not caspase-3, is observed before onset of motor abnormalities in human and murine HD brain. Active casp6 levels correlate directly with CAG size and inversely with age of onset. In contrast, in vivo expression of C6R mhtt attenuates caspase activation. Increased casp6 activity and apoptotic cell death is evident in primary striatal neurons expressing caspase-cleavable, but not C6R, mhtt after NMDA application. Pretreatment with a casp6 inhibitor rescues the apoptotic cell death observed in this paradigm. These data demonstrate that activation of casp6 is an early marker of disease in HD. Furthermore, these data provide a clear link between excitotoxic pathways and proteolysis and suggest that C6R mhtt protects against neurodegeneration by influencing the activation of neuronal cell-death and excitotoxic pathways operative in HD.
Antibiotic resistance of Salmonella typhi in Bangladesh (1994)

Journal Article Antibiotic resistance of Salmonella typhi in Bangladesh Get access SAMIR K. SAHA, SAMIR K. SAHA Search for other works by this author on: Oxford Academic PubMed Google Scholar SOUMITRA K. SAHA SOUMITRA K. SAHA Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Antimicrobial Chemotherapy, Volume 33, Issue 1, January 1994, Pages 190–191, https://doi.org/10.1093/jac/33.1.190 Published: 01 January 1994
Rapid Detection of Acute Kidney Injury by Plasma and Urinary Neutrophil Gelatinase-associated Lipocalin After Cardiopulmonary Bypass (2009)

Measurement of this novel biomarker in the urine or plasma of patients in the first hours after CPB is predictive of subsequent renal injury. Although the AUC for plasma NGAL seemed inferior to urine, even an AUC of 0.8 as reported compares very favorably to that for other "outstanding" biomarkers (eg, AUCs in the 0.7 range for troponin).
The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum (2003)

Here we report on the action of the novel cyclo-depsipeptide anthelmintic, emodepside, on the body wall muscle of the parasitic nematode, Ascaris suum. Emodepside caused (i) muscle relaxation, (ii) inhibition of muscle contraction elicited by either acetylcholine (ACh), or the neuropeptide, AF2 (KHEYLRFamide) and (iii) a rapid relaxation of muscle tonically contracted by ACh. The inhibitory action of emodepside on the response to ACh was not observed in a denervated muscle strip, indicating that it may exert this action through the nerve cord, and not directly on the muscle. Electrophysiological recordings showed emodepside elicited a Ca(++)-dependent hyperpolarization of muscle cells. Furthermore, the response to emodepside was dependent on extracellular K+, similar to the action of the inhibitory neuropeptides PF1 and PF2 (SDPNFLRFamide and SADPNFLRFamide). Thus emodepside may act at the neuromuscular junction to stimulate release of an inhibitory neurotransmitter or neuromodulator, with a similar action to the PF1/PF2 neuropeptides.
Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. (2003)

Preclinical studies have shown that low dose IL-12 can potentiate cytotoxic lymphocyte responses. Since previous trials have demonstrated significant toxicity from high dose recombinant human IL-12 (rhIL-12), we sought to determine an optimal biological dose for rhIL-12 at lower doses when combined with peptide antigens. Two studies were undertaken. The rhIL-12 was administered at doses of 0 (placebo), 10, 30 and 100 ng/kg, subcutaneously in one study and intravenously in the other. Apart from IL-12 dosing, the studies were identical. Subjects had evaluable stage III or IV melanoma which expressed Melan-A by RT-PCR or immunohistochemistry. Melan-A (26-35) (EAAGIGILTV) and influenza matrix (58-66) (GILGFVFTL) peptides were administered intradermally on weeks 1, 2, 3, 4 and 9. Twenty-eight subjects were enrolled, of whom 24 were evaluable for clinical and immunological responses. Therapy was well tolerated, the main adverse event being influenza-like symptoms. Immunological monitoring included the evaluation of cutaneous reactions and assays for antigen-specific T-cells. Clinical responses included a complete response in a subject with small volume subcutaneous disease, a partial response in a subject with hepatic metastases, and mixed responses in pulmonary, pleural and nodal disease. Biopsies of accessible tumors showed infiltration with CD4+ and CD8+ lymphocytes capable of lysing Melan-A peptide-pulsed targets in vitro. No clear dose-dependent effect of rhIL-12 could be determined. The rhIL-12 given either s.c. or i.v. was well tolerated at doses of 10-100 ng/kg. Clinical and immunological activity has been observed in this study where peptides were administered either with or without low dose rhIL-12.
Is Glycemic Control Improving in U.S. Adults? (2007)

Glycemic control improved between 1999 and 2004. This trend may represent an important improvement in diabetes care and is encouraging for future reduction of diabetes-related complications.
Phase I/II clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 in patients with unresactable, chemotherapy-resistant peritoneal carcinomatosis. (2013)

3098 Background: For therapy-resistant peritoneal carcinomatosis (PC) viruses exhibiting oncolytic properties open up new perspectives. Our phase I/II study in patients with refractory PC (NCT01443260) is designed to assess the safety, MTD, and anti-tumor activity of GL-ONC1, a recombinant vaccinia virus (VACV) genetically engineered to selectively replicate in and destroy cancer cells. Methods: GL-ONC1 was administered intraperitoneally up to 4 times every 28 days under a standard 3+3 dose escalation design. Safety was assessed using CTCAEv4.0. Anti-tumor activity was determined by “fluid biopsies” obtained via repetitive paracenteses and by serial PET-CT scans. Patient samples were collected for pharmacokinetics, pharmacodynamics and viral shedding analysis. Results: Up to now, 4 patients have received 10 doses of GL-ONC1 ranging from 10 7 to 10 8 infectious viral particles per application.Adverse events have generally been limited to grade 1/2, being mostly transient flu-like symptoms as well as increased abdominal pain resulting from treatment-induced peritonitis. No DLT was reported. No viral shedding was observed. In one gastric cancer patient, effective intraperitoneal replication of GL-ONC1 was demonstrated for more than 3 weeks. Using either anti-EpCAM or anti-VACV specific antibodies, around 5% of all ascitic cells were found to be EpCAM-positive 3 days after treatment in this patient, and only around 5-10% of these cancer cells were VACV positive at the same time point. In contrast, 4 days later (i.e. 7 days after virotherapeutic treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. Of note, VACV-positive cancer cells morphologically showed significant degenerative changes. Conclusions: Preliminary data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally. Importantly, a single intraperitoneal delivery of GL-ONC1 was found to be sufficient to cause a dramatic decline in the number of malignant cells in the ascitic fluid, suggesting that GL-ONC1 effectively removes tumor cells in the ascites of patients with PC. Clinical trial information: NCT01443260.
A Neuronal Antigen in the Brains of Alzheimer Patients (1986)

A monoclonal antibody was prepared against pooled homogenates of brain tissue from patients with Alzheimer's disease. This antibody recognizes an antigen present in much higher concentration in certain brain regions of Alzheimer patients than in normal brain. The antigen appears to be a protein present in neurons involved in the formation of neuritic plaques and neurofibrillary tangles, and in some morphologically normal neurons in sections from Alzheimer brains. Partial purification and Western blot analysis revealed the antigen from Alzheimer brain to be a single protein with a molecular weight of 68,000. Application of the same purification procedure to normal brain tissue results in the detection of small amounts of a protein of lower molecular weight.
Cyclic sulfolanes as novel and high-affinity P2 ligands for HIV-1 protease inhibitors (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic sulfolanes as novel and high-affinity P2 ligands for HIV-1 protease inhibitorsArun K. Ghosh, Wayne J. Thompson, Hee Yoon Lee, Sean P. McKee, Peter M. Munson, Tien T. Duong, Paul L. Darke, Joan A. Zugay, Emilio A. Emini, and Cite this: J. Med. Chem. 1993, 36, 7, 924–927Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/jm00059a019https://doi.org/10.1021/jm00059a019research-articleACS PublicationsRequest reuse permissionsArticle Views280Altmetric-Citations42LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Reinforcement Learning Neural Turing Machines (2015)

The expressive power of a machine learning model is closely related to the number of sequential computational steps it can learn. For example, Deep Neural Networks have been more successful than shallow networks because they can perform a greater number of sequential computational steps (each highly parallel). The Neural Turing Machine (NTM) [8] is a model that can compactly express an even greater number of sequential computational steps, so it is even more powerful than a DNN. Its memory addressing operations are designed to be differentiable; thus the NTM can be trained with backpropagation. While differentiable memory is relatively easy to implement and train, it necessitates accessing the entire memory content at each computational step. This makes it difficult to implement a fast NTM. In this work, we use the Re inforce algorithm to learn where to access the memory, while using backpropagation to learn what to write to the memory. We call this model the RL-NTM. Reinforce allows our model to access a constant number of memory cells at each computational step, so its implementation can be faster. The RL-NTM is the first mo del that can, in principle, learn programs of unbounded running time. We successfully trained the RL-NTM to solve a number of algorithmic tasks that are simpler than the ones solvable by the fully differentiable NTM. As the RL-NTM is a fairly intricate model, we needed a method for verifying the correctness of our implementation. To do so, we developed a simple technique for numerically checking arbitrary implementations of models that use Reinforce, which may be of independent interest.
Autologous Fibrin Glue in Full-thickness Skin Grafting (1989)

Full-thickness skin grafts can be anchored to the recipient site using fibrin glue made from the patient's own blood and commercially available thrombin and epsilon aminocaproic acid. The technique works well for small grafts on irregularly contoured sites where suture fixation of a graft would be technically difficult. Full-thickness skin grafts anchored with autologous fibrin glue have been uniformly successful in 50 patients followed for a minimum period of four months.
Increased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages (2002)

The ATP-binding cassette transporter A1 (ABCA1) encodes a membrane protein that promotes cholesterol and phospholipid efflux from cells. Mutations in ABCA1 lead to HDL deficiency and tissue accumulation of macrophages in patients with homozygous Tangier disease. In this study, we examined whether the complete absence of ABCA1 or selected inactivation in macrophages is accompanied by an increase in atherosclerotic lesion progression in hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) mice and LDLR receptor-deficient (LDLr(-/-)) mice. The absence of ABCA1 led to reduced plasma cholesterol levels in both the apoE(-/-) and LDLr(-/-) mice, along with severe skin xanthomatosis characterized by marked foamy macrophages and cholesterol ester accumulation. However, the complete absence of ABCA1 did not affect the development, progression, or composition of atherosclerotic lesions in either the LDLr(-/-) or the apoE(-/-) mice fed a chow or atherogenic diet. In contrast, bone marrow transplantation studies demonstrated that the selective inactivation of ABCA1 in macrophages markedly increased atherosclerosis and foam cell accumulation in apoE(-/-). Taken together, these findings demonstrate that the complete absence of ABCA1 has a major impact on plasma lipoprotein homeostasis, and the proposed antiatherogenic effect resulting from ABCA1 deficiency is compensated by a less atherogenic profile. ABCA1 deficiency in macrophages, however, demonstrates the antiatherogenic properties of ABCA1 independent of plasma lipids and HDL levels.
Compliance with and Attitudes towards the Management of Medical Emergencies in General Dental Practice (2014)

Patient safety and risk management are increasing priorities in dental practice today. Ensuring that members of the dental team are prepared and equipped to adequately manage the common medical emergencies that might occur is an expectation of the public and increasingly demanded by the inspecting and regulatory bodies in healthcare.
Role of protein disulphide-isomerase in the expression of native proteins. (1989)

Formation of native disulphide bonds is a post-translational modification associated with the folding and assembly of secretory proteins. The process is catalysed within the lumen of the endoplasmic reticulum by the enzyme protein disulphide-isomerase (PDI), which is abundant in secretory cells and catalyses thiol: protein-disulphide interchange in vitro with very broad protein substrate specificity. The presence of PDI within microsomal vesicles is essential for efficient and rapid cotranslational disulphide bond formation during protein synthesis in vitro. The sequence of PDI is now known from several species, and shows the presence of two domains closely homologous to thioredoxins. Chemical modification data confirm the role of the thioredoxin domains in thiol:disulphide interchange activity, and structural models of these domains can be built based on homology with thioredoxin. Thus PDI is both strongly implicated in the process of native protein folding in vivo and well characterized at the molecular level. In addition to its disulphide-isomerase activity, PDI participates as a component of the enzyme prolyl-4-hydroxylase, and further functions have also been proposed.
Optimal and near‐optimal filters in high‐resolution electron microscopy (1998)

Two filters for improving the visibility of crystalline material in the presence of amorphous surface contamination layers in high‐resolution electron microscope images can be constructed automatically from the information present in the Fourier transform of the recorded image. The recorded signal is considered in the first approximation to be the sum of two signals which are uncorrelated in the frequency domain. By estimating the power spectrum of the signal from the amorphous layer, an optimized estimate for the desired signal is given by the Wiener filter. A second filter which uses the estimated amplitude of the amorphous signal to subtract out a background can be shown to be related to the Wiener filter. The two filters are applied to an experimental image of zeolite and the effects of the two filters are compared.
Medical male circumcision campaigns face cultural challenges in southern Africa : AIDS brief (2013)

Campaigns to circumcise tens of thousands of men in southern Africa are falling victim to lingering acceptability issues six years after the procedure was first recommended to help prevent HIV infection, according to speakers at the 2nd International Conference for the Social Sciences and Humanities in HIV in Paris last week.
WHAT SIZE SHOULD A BACTERIUM BE? A Question of Scale (1996)

There are living prokaryotes (Bacteria and Archaea) that have cell sizes that range from 0.02-400 microns3. Over this tremendous range, various abilities to cope with the environment are needed. This review attempts to formulate some of the problems and some of the solutions. The smallest size for a free-living organism is suggested to be largely set by the catalytic efficiency of enzymes and protein synthetic machinery. Because of fluctuations in the environment, cells must maintain machinery to cope with various catastrophes; these mechanisms increase the minimum size of the cell. On the other hand, the largest cell is reasonably assumed to be limited by the ability of diffusion to bring nutrients to the appropriate part of the cell and to dispose of waste products. To explore the limitation imposed by diffusion, analysis is developed of diffusion processes through stirred and unstirred media, diffusion through media that contains obstacles, and the effect of size and shape.
Quantum biomechanics of long-range electron transfer in protein: hydrogen bonds and reorganization energies. (1994)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Modeling of Surrounding Gate MOSFETs With Bulk Trap States (2007)

We report a simple analytical model for surrounding gate MOSFETs including bulk traps. Based on the depletion approximation and the assumption that bulk traps are uniformly distributed inside the bandgap, we solved Poisson's equation in cylindrical coordinates and derived the general solution of potential distribution. Extraction of threshold voltage and subthreshold slope were conducted. The analytical solution yields good agreement with MEDICI simulations confirming the model. The model predicts a linear threshold voltage drop, depending on the trap density, as the diameter of the device decreases when the channel is fully depleted
Testing and Analysis of Thin Stiffened Composite Shear Panels (1995)

An investigation of theoretical and experimental approaches to the characterisation of thin, stiffened, composite panels in the postbuckled state has been undertaken. Static shear tests were performed on three-blade-stiffened panels with a working section of 250 mm square using a 'picture frame' test rig. Several panels with an introduced delamination were also tested. A servo-hydraulic testing machine was employed for loading the panels. Buckling initiated at 26 kN (74 N/mm) and a fully buckled tension field developed at 31 kN (88 N/mm). The panels failed at loads in excess of three times the initial buckling load. A finite element model of the panel was developed using linear and geometrically nonlinear solution methods. The predicted buckling load, displacements and strains compared well with experiment.
Chemopreventive promise of targeting the Nrf2 pathway (2007)

The Kelch ECH associating protein 1-nuclear factor-E2-related factor 2-antioxidant response element (Keap 1-Nrf2-ARE) signaling pathway regulates several protective mechanisms including expression of conjugating and antioxidative genes, antiinflammatory responses, the molecular chaperone/stress response system and the ubiquitin/proteasome system. The Nrf2-mediated response alters susceptibility to carcinogenesis, acute chemical toxicity, oxidative stress, asthma, acute inflammation, septic shock and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Studies using natural and synthetic chemical inducers that activate Nrf2 signaling have demonstrated protective efficacy in many animal models of disease. Conversely, studies in Nrf2-disrupted mice indicate they exhibit increased sensitivity to many of these diseases. Thus, activation of Keap1-Nrf2-ARE signaling constitutes a broad protective response, making Nrf2 and its interacting partners important targets for chemoprevention. However, additional studies are needed to characterize Keap1-Nrf2-ARE signaling in humans to further develop exceptionally potent activators of the pathway and further understand the potential consequences of altering this system.
Reclassification of Eubacterium rectale (Hauduroy et al. 1937) Prévot 1938 in a new genus Agathobacter gen. nov. as Agathobacter rectalis comb. nov., and description of Agathobacter ruminis sp. nov., isolated from the rumen contents of sheep and cows (2015)

Three strains of a butyrate-producing bacterium were isolated from the rumen contents of grazing sheep and cows. The strains were anaerobic, with Gram-positive cell walls, straight-to-slightly-curved, rod-shaped, non-spore-forming and single flagellate. C<sub>14 : 1</sub>, C<sub>14 : 0</sub>, C<sub>16 : 0</sub> and C<sub>16 : 1</sub> were the predominant fatty acids. The cell-wall peptidoglycan type was A1<i>γ</i>. The DNA G+C content varied from 41.4 to 42.2 mol%. 16S rRNA gene sequence similarities between the isolates and <i>Eubacterium rectale</i>, <i>Roseburia hominis</i> and <i>Roseburia intestinalis</i> were found to be 96, 95 and 95 %, respectively. The phylogenetic tree showed that the strains constituted a different taxon, separate from other taxa with validly published names and forming a cluster with strains of <i>Eubacterium rectale.</i> On the basis of phenotypic, chemotaxonomic and phylogenetic results (16S RNA, <i>dnaK</i>, <i>groEL</i>, <i>atpA</i> genes), the isolates are considered to represent a novel species of a new genus of the family <i>Lachnospiraceae</i>, for which the name <i>Agathobacter ruminis</i> gen. nov., sp. nov. is proposed (type strain JK623<sup>T</sup> = DSM 29029<sup>T</sup> = LMG 28559<sup>T</sup>). We also propose the transfer of <i>Eubacterium rectale</i> to the new genus <i>as Agathobacter rectalis</i> gen. nov., comb nov. This new genus represents saccharoclastic, chemo-organotrophic and obligatory anaerobic, non-spore-forming rods with Gram-positive membrane. The main fermentation products on peptone yeast glucose (PYG) medium were butyrate, acetate, hydrogen and lactate. The type species of the genus is <i>Agathobacter rectalis</i> gen. nov., comb nov. (Prévot, 1938) with type strain ATCC 33656<sup>T</sup> ( = JCM 17463<sup>T</sup>).