gebhart/patrepeval huggingface dataset:
Time- and Temperature-Dependent Activation of Hepatitis C Virus for Low-pH-Triggered Entry (2006)

Hepatitis C virus (HCV) is an important human pathogen associated with chronic liver disease. Recently, based on a genotype 2a isolate, tissue culture systems supporting complete replication and infectious virus production have been developed. In this study, we used cell culture-produced infectious HCV to analyze the viral entry pathway into Huh-7.5 cells. Bafilomycin A1 and concanamycin A, inhibitors of vacuolar ATPases, prevented HCV entry when they were present prior to infection and had minimal effect on downstream replication events. HCV entry therefore appears to be pH dependent, requiring an acidified intracellular compartment. For many other enveloped viruses, acidic pH triggers an irreversible conformational change, which promotes virion-endosomal membrane fusion. Such viruses are often inactivated by low pH. In the case of HCV, exposure of virions to acidic pH followed by return to neutral pH did not affect their infectivity. This parallels the observation made for the related pestivirus bovine viral diarrhea virus. Low pH could activate the entry of cell surface-bound HCV but only after prolonged incubation at 37 degrees C. This suggests that there are rate-limiting, postbinding events that are needed to render HCV competent for low-pH-triggered entry. Such events may involve interaction with a cellular coreceptor or other factors but do not require cathepsins B and L, late endosomal proteases that activate Ebola virus and reovirus for entry.
β‐Mannosidase deficiency in a female infant with epileptic encephalopathy (1990)

We report a female infant with an isolated deficiency of beta-mannosidase activity. At nine months of age dysmorphism was absent except for brachecephaly. There was moderate developmental delay and a startle response to sound. At 12 months there was a sudden onset of tonic-clonic seizures which were unresponsive to drug therapy, requiring paralysis and mechanical ventilation for control. The child died suddenly aged 15 months. beta-mannosidase activity was markedly reduced in white cells and cultured skin fibroblasts whilst other lysosomal enzymes were normal. The disaccharide ManGlcNAc was excreted in urine but urinary mucopolysaccharides were normal.
Beyerane diterpenes: structure and reactivity of the α-ketol ent-3β-hydroxybeyer-15-ene-2,12-dione, its corresponding diosphenol, and synthesis of the isomeric α-ketol acetates (1979)

The major diterpenoid constituents of the heartwood of the Euphorbiaceae Androstachys johnsonii Prain are ent-3β-hydroxybeyer-15-ene-2,12-dione and the corresponding 2,3,12-trione. The four isomeric 2,3-α-ketol acetates were prepared by new and established methods and the chemistry of these α-ketols was investigated. A condensation reaction with ethylene glycol led to the useful ring A 2,3-ethylenedioxy blocking group. The 12-equatorial alcohol was eliminated yielding the new tetracyclic skeleton ent-14(13 → 12)abeo-beyerane. The ent-3β-hydroxy-2-ketone function was epimerised to the ent-3α-acetoxy-2-ketone function via the derived pyrrolidine enamine.
A microelectrochemical diode with submicron contact spacing based on the connection of two microelectrodes using dissimilar redox polymers (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA microelectrochemical diode with submicron contact spacing based on the connection of two microelectrodes using dissimilar redox polymersGregg P. Kittlesen, Henry S. White, and Mark S. WrightonCite this: J. Am. Chem. Soc. 1985, 107, 25, 7373–7380Publication Date (Print):December 1, 1985Publication History Published online1 May 2002Published inissue 1 December 1985https://pubs.acs.org/doi/10.1021/ja00311a026https://doi.org/10.1021/ja00311a026research-articleACS PublicationsRequest reuse permissionsArticle Views257Altmetric-Citations96LEARN 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-Alertsclose Get e-Alerts
Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families. (1994)

The entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.
<title>Neural network benchmark</title> (1997)

In this paper, we will present a Neural Net Benchmark. In many neural algorithms, learning is defined as a change in connection weight values that result in the capture of training information that can later be recalled. A typical learning algorithm is: if neuron A was active and A's activity caused a connected neuron B to fire, then the synaptic connection between A and B should be increased by certain amount. The benchmark systematically tests a neural network for this ability. The benchmark can be written as: (L3, L4, L5, L6, ... ...). L3 tests the net's ability for 3- neuron correlation: if A and B were active and A and B's activity caused a connected neuron C to fire, can the network recall it later? Similarly, L4, L5, ... tests a net for 4-neuron, 5-neuron correlation. We will also present a neural net classification based on the benchmark.
Purine analogues as amplifiers of phleomycin. VII. Some 1H-imidazo-[4,5-b]pyrazines and related compounds (1982)

Preparations of 2-hydroxy- and 2-mercapto-1H-imidazo[4,5-blpyrazines from pyrazine-2,3-diamines are described. Methylation of 1H-imidazo[4,5- b ]pyrazine-2(3 H )-thione with methyl iodide and diazomethane gave some S, N1, N3 and N4 methyl derivatives; and 1H-imidazo[4,5-b]pyrazin- 2(3H)-one with diazomethane gave products which involved O , N1, N3 and N4 methylation. These products showed slight activity as amplifiers of phleomycin but the benzothiazoles (10b) and (10c) (as hydrobromides) showed three and four star activity respectively.
Determining the Delamination Propensity of Pharmaceutical Glass Vials Using a Direct Stress Method (2013)

Glass flakes can sometimes appear in liquid pharmaceutical drugs contained in glass vials. These glass flakes are a result of several factors related to the glass vial production process, glass vial sterilization procedures, and the formulation of the liquid pharmaceutical drug. Vial testing is routinely done in order to select glass vials that are less likely to form glass flakes. The factors leading to the formation of glass flakes were studied and applied to a method designed to directly screen vials for their propensity to form glass flakes. The washing of vials followed immediately by sterilization at high temperatures was determined to be a critical factor in the formation of glass flakes. As a result, a laboratory mimic of this procedure was incorporated into the newly developed method for screening vials. This mimic procedure as well as robust accelerated incubation conditions and a sensitive visual inspection procedure are key aspects of this vial screening method.
Relation between image-based assessment of distal radius trabecular structure and compressive strength. (1998)

Our findings suggest that image-based assessments of trabecular bone structure relate to bone strength in vitro.
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study (2007)

Alleles of IL2RA and IL7RA and those in the HLA locus are identified as heritable risk factors for multiple sclerosis.
Use of fluorescein-di-beta-D-galactopyranoside (FDG) and C12-FDG as substrates for beta-galactosidase detection by flow cytometry in animal, bacterial, and yeast cells (1994)

Fluorescein-di-beta-D-galactopyranoside (FDG) was found to be a useful substrate for beta-galactosidase detection by flow cytometry in gram-negative bacteria, since it entered viable cells and gave a fluorescence emission proportional to the enzymatic activity. C12-FDG, a more lipophilic derivative, gave a very poor signal because of the lack of penetration. On the contrary, C12-FDG was more sensitive than FDG for beta-galactosidase activity determinations in animal cells. In contrast to previous reports, C12-FDG did not enter viable yeast cells, so that the use of the substrate required cell permeabilization. Without this treatment, C12-FDG penetrates only nonviable yeast cells that may occur in populations expressing beta-galactosidase.
The Hill equation: a review of its capabilities in pharmacological modelling (2008)

The Hill equation was first introduced by A.V. Hill to describe the equilibrium relationship between oxygen tension and the saturation of haemoglobin. In pharmacology, the Hill equation has been extensively used to analyse quantitative drug-receptor relationships. Many pharmacokinetic-pharmacodynamic models have used the Hill equation to describe nonlinear drug dose-response relationships. Although the Hill equation is widely used, its many properties are not all well known. This article aims at reviewing the various properties of the Hill equation. The descriptive aspects of the Hill equation, in particular mathematical and graphical properties, are examined, and related to Hill's original work. The mechanistic aspect of the Hill equation, involving a strong connection with the Guldberg and Waage law of mass action, is also described. Finally, a probabilistic view of the Hill equation is examined. Here, we provide some new calculation results, such as Fisher information and Shannon entropy, and we introduce multivariate probabilistic Hill equations. The main features and potential applications of this probabilistic approach are also discussed. Thus, within the same formalism, the Hill equation has many different properties which can be of great interest for those interested in mathematical modelling in pharmacology and biosciences.
Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation (2003)

Subanaesthetic doses of the N-methyl-D-aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non-NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg-1 min-1, I.V.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P < 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P < 0.001). Before ketamine administration, mean RMT +/- S.D. was 49 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 +/- 2.6 % (P < 0.001). Before ketamine administration, AMT +/- S.D. was 38 +/- 3.3 % of maximum stimulator output and at the highest infusion level it was 33 +/- 4.4 % (P < 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P = 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high-frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short-lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non-NMDA receptors similar to that described in experimental studies.
Standardization of measurement of β-amyloid(1-42)in cerebrospinal fluid and plasma (2000)

The standardization and clinical validation of the measurement of beta-amyloid(1-42) (Abeta42) in cerebrospinal fluid (CSF), plasma and urine is described using a commercially available sandwich-type ELISA with 21F12 and 3D6 as monoclonal antibodies. The INNOTEST beta-amyloid(1-42) allows the specific and reliable measurement of(1-42) amyloid peptides in CSF and plasma. The Abeta42 concentrations in serum and urine were below the detection limit. In plasma, no differences were found in Abeta42 levels between controls and patients with different neurodegenerative disorders (Alzheimer's disease (AD), Lewy body disease (LBD), others). In contrast, CSF-Abeta42 concentrations were lower in AD and LBD patients as compared to controls. No correlation was found in AD patients between CSF and plasma concentrations of Abeta42 or between CSF Abeta42 levels and blood-brain-barrier function. The quantitative outcome of the test is in part dependent on confounding factors such as tube type, freeze/thaw cycles, temperature of incubation, standard preparation protocol, and antibody selection. Notwithstanding these aspects, it emerged that Abeta42 is a useful biochemical marker for the diagnosis of AD patients, but there is a need for an international Abeta standard, a universally accepted protocol for CSF preparation, and a thorough evaluation of assay performance in function of the boundary conditions.
Inositol polyanions. Noncarbohydrate inhibitors of L- and P-selectin that block inflammation. (1994)

Selectins are cell adhesion molecules known to support the initial attachment of leukocytes to inflamed vascular endothelium through their recognition of carbohydrate ligands such as the tetrasaccharide sialyl Lewisx (Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc-). In the present study, we describe the inhibition of L- and P-selectin function by inositol polyanions, simple 6-carbon ring structures that have multiple ester-linked phosphate or sulfate groups. In a purified component competition assay, binding of L- and P-selectin-Ig fusion proteins to immobilized bovine serum albumin-sialyl Lewisx neoglycoprotein was inhibited by inositol hexakisphosphate (InsP6, IC50 = 2.1 +/- 1.4 microM and 160 +/- 40 microM), by inositol pentakisphosphate (InsP5, IC50 = 1.4 +/- 0.2 and 260 +/- 40 microM), and by inositol hexakissulfate (InsS6, IC50 = 210 +/- 80 microM and 2.8 +/- 0.9 mM); E-selectin-Ig binding was unaffected. Inositol polyanions diminished the adhesion of LS180 colon carcinoma cells to plates coated with L- and P-selectin-Ig but not with E-selectin-Ig. Inositol polyanions blocked polymorphonuclear leukocyte (PMN) adhesion to COS cells expressing recombinant transmembrane P-selectin but not to those expressing E-selectin. In addition, inositol polyanions diminished PMN adhesion to activated endothelial cells under rotation-induced shear stress, a process known to require L-selectin function. In vivo, the effects of inositol polyanions were studied in two murine models of acute inflammation. Intravenously administered InsP6 (two doses of 40 mumol/kg) inhibited PMN accumulation in thioglycolate-induced inflammation (55 +/- 10% inhibition) and in zymosan-induced inflammation (61 +/- 4% inhibition). InsP5 and InsS6 also inhibited inflammation in these models, although higher doses were required for InsS6. In conclusion, inositol polyanions are noncarbohydrate small molecules that inhibit L- and P-selectin function in vitro and inflammation in vivo.
Non-thermal Plasma Inactivation of Bacillus Amyloliquefaciens spores (2011)

Inactivation of Bacillus amyloliquefaciens (BA) spores by non-thermal plasma (NTP) was investigated by studying inactivation kinetics and using attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR). ATR-FTIR is a useful tool to probe the biochemical and structural changes of spores after NTP treatment in order to better manipulate and optimize the parameters for NTP processing. The microdischarge generated by the dielectric barrier in our research has higher energy efficiency compared with a uniform glow discharge at atmospheric pressure and autoclave. The survival curve showed two phases with different spore inactivation rates and changes in surface topography of the spores assessed by atomic force microscopy (AFM) indicating that NTP treatment disrupted spore aggregates so that reactive species could reach and inactivate the bottom layers of spore films. Scanning electron microscopy (SEM) images showed that the spore surface was etched away after NTP treatment. Multivariate classification models based on Soft Independent Modeling of Class Analogy (SIMCA) were developed to identify the biochemical changes after NTP treatment. The absorbance of bands correlated to dipicolinic acid (DPA) ring decreased after NTP treatment indicating that DPA released and then reacted with reactive species generated by plasma, which was confirmed by NMR spectra. Also bands corresponding to protein structure changed after NTP treatment.
Quality of newborn care: adherence to guidelines for parenteral nutrition in preterm infants in four European countries (2013)

Most respondents indicated that their clinical practice was based on common guidelines. However, the initiation of PN is frequently not compliant with current recommendations, with the main differences being observed during the first days of life. Continuous education focusing on PN practice is needed, and greater efforts are required to disseminate and implement international guidelines.
Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control (2007)

Based on these results, we propose that RhoA/ROCK blockade constitutes a novel approach to the treatment of diabetic nephropathy. Our data also suggest a critical role for RhoA/ROCK activation in the pathogenesis of diabetic nephropathy.
Studies on the Species Specificity of Yeast and E. coli Tyrosine tRNAs (1966)

As an adaptor, the transfer RNA molecule should have three functional sites. One site recognizes the specific aminoacyl tRNA synthetase, and thus the tRNA can accept a specific amino acid. The second site recognizes the correct codon on the template or messenger RNA; and a third, which may be common to all tRNAs, furnishes a binding site for the tRNA on the ribosome.
Dynamic Time Warping As a Novel Tool in Pattern Recognition of ECG Changes in Heart Rhythm Disturbances (2006)

We present a novel method for the classification and identification of electrocardiograms (ECGs) of various heart rhythm disturbances. This is an essential step in the automatic analysis of heart rhythm disturbances. Dynamic time warping (DTW) is used for this purpose. DTW is utilized successfully in speech recognition. Wavelet analysis is used in some implantable cardioverter defibrillators currently for ECG waveform recognition and classification purpose. The simulations of time-series ECG data of various rhythm disturbances are produced. Normal sinus rhythm ECG templates are compared to the simulated rhythms by both methods. DTW analysis successfully differentiates the ECGs of various arrhythmias. Of note, DTW is able to differentiate ventricular tachycardia from supraventricular tachycardia unlike wavelet analysis. Differentiation of these two rhythm types has significant clinical implications. DTW can potentially be used for automatic pattern recognition of ECG changes representative of various rhythm disturbances.
Multi-cell type human liver microtissues for hepatotoxicity testing (2012)

Current 2-dimensional hepatic model systems often fail to predict chemically induced hepatotoxicity due to the loss of a hepatocyte-specific phenotype in culture. For more predictive in vitro models, hepatocytes have to be maintained in a 3-dimensional environment that allows for polarization and cell-cell contacts. Preferably, the model will reflect an in vivo-like multi-cell type environment necessary for liver-like responses. Here, we report the characterization of a multi-cell type microtissue model, generated from primary human hepatocytes and liver-derived non-parenchymal cells. Liver microtissues were stable and functional for 5 weeks in culture enabling, for example, long-term toxicity testing of acetaminophen and diclofenac. In addition, Kupffer cells were responsive to inflammatory stimuli such as LPS demonstrating the possibility to detect inflammation-mediated toxicity as exemplified by the drug trovafloxacin. Herewith, we present a novel 3D liver model for routine testing in 96-well format capable of reducing the risk of unwanted toxic effects in the clinic.
Functionally Accepted Insertions of Proteins within Protein Domains (2000)

Experiments were designed to explore the tolerance of protein structure and folding to very large insertions of folded protein within a structural domain. Dihydrofolate reductase and beta-lactamase have been inserted in four different positions of phosphoglycerate kinase. The resultant chimeric proteins are all overexpressed, and the host as well as the inserted partners are functional. Although not explicitly designed, functional coupling between the two fused partners was observed in some of the chimeras. These results show that the tolerance of protein structures to very large structured insertions is more general than previously expected and supports the idea that the natural sequence continuity of a structural domain is not required for the folding process. These results directly suggest a new experimental approach to screen, for example, for folded protein in randomized polypeptide sequences.