gebhart/patrepeval huggingface dataset:
Drug-induced liver injury: recent advances in diagnosis and risk assessment (2017)

Idiosyncratic drug-induced liver injury (IDILI) is a rare but potentially severe adverse drug reaction that should be considered in patients who develop laboratory criteria for liver injury secondary to the administration of a potentially hepatotoxic drug. Although currently used liver parameters are sensitive in detecting DILI, they are neither specific nor able to predict the patient's subsequent clinical course. Genetic risk assessment is useful mainly due to its high negative predictive value, with several human leucocyte antigen alleles being associated with DILI. New emerging biomarkers which could be useful in assessing DILI include total keratin18 (K18) and caspase-cleaved keratin18 (ccK18), macrophage colony-stimulating factor receptor 1, high mobility group box 1 and microRNA-122. From the numerous in vitro test systems that are available, monocyte-derived hepatocytes generated from patients with DILI show promise in identifying the DILI-causing agent from among a panel of coprescribed drugs. Several computer-based algorithms are available that rely on cumulative scores of known risk factors such as the administered dose or potential liabilities such as mitochondrial toxicity, inhibition of the bile salt export pump or the formation of reactive metabolites. A novel DILI cluster score is being developed which predicts DILI from multiple complimentary cluster and classification models using absorption-distribution-metabolism-elimination-related as well as physicochemical properties, diverse substructural descriptors and known structural liabilities. The provision of more advanced scientific and regulatory guidance for liver safety assessment will depend on validating the new diagnostic markers in the ongoing DILI registries, biobanks and public-private partnerships.
Physical Chemistry of Protein Solutions. VII. The Binding of Some Small Anions to Serum Albumin1 (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysical Chemistry of Protein Solutions. VII. The Binding of Some Small Anions to Serum Albumin1George Scatchard, James S. Coleman, and Amy L. ShenCite this: J. Am. Chem. Soc. 1957, 79, 1, 12–20Publication Date (Print):January 1, 1957Publication History Published online1 May 2002Published inissue 1 January 1957https://pubs.acs.org/doi/10.1021/ja01558a003https://doi.org/10.1021/ja01558a003research-articleACS PublicationsRequest reuse permissionsArticle Views357Altmetric-Citations330LEARN 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
Malaria vaccines in development (2005)

The recent infusion of public and private funding for malaria vaccine development has greatly accelerated the pace at which candidate malaria vaccines are entering the clinic. Recent promising results from vaccine trials carried out in malaria-naive and -endemic populations have revealed important insights into what will be required of a successful vaccine. Significant challenges lie ahead, not the least of which is insuring access of a malaria vaccine to the populations that need it most. Creative strategies, strong partnerships with developing countries, industry-like approaches to product development, and political vision and leadership on the part of wealthy nations will be critical to the successful implementation of this important new tool to reduce the intolerable burden of malaria.
Backward peak in the electron spectrum from collisions of 70-keV protons with a target from a hydrogen-atom source (1992)

A large, broad peak has been found in the electron energy spectrum from 30 to 100-keV ${\mathrm{H}}^{+}$+H collisions. The peak, which is centered at 31 eV, appears only in the backward directions. It is suggested that while the peak is unlikely to come from collisions with atoms in the ground or metastable states, it could arise from collisions with atoms in highly excited states or from autoionizing states of the residual ${\mathrm{H}}_{2}$ in the target.
Extension of helix II of an HIV-1-directed hammerhead ribozyme with long antisense flanks does not alter kinetic parametersin vitrobut causes loss of the inhibitory potential in living cells (1994)

When designed to cleave a target RNA in trans, the hammerhead ribozyme contains two antisense flanks which form helix I and helix III by pairing with the complementary target RNA. The sequences forming helix II are contained on the ribozyme strand and represent a major structural component of the hammerhead structure. In the case of an inhibitory 429 nucleotides long trans-ribozyme (2as-Rz12) which was directed against the 5'-leader/gag region of the human immunodeficiency virus type 1 (HIV-1), helix II was not pre-formed in the single-stranded molecule. Thus, major structural changes are necessary before cleavage can occur. To study whether pre-formation of helix II in the non-paired 2as-Rz12 RNA could influence the observed cleavage rate in vitro and its inhibitory activity on HIV-1 replication, we extended the 4 base pair helix II of 2as-Rz12 to 6, 10, 21, and 22 base pairs respectively. Limited RNase cleavage reactions performed in vitro at 37 degrees C and at physiological ion strength indicated that a helix II of the hammerhead domain was pre-formed when its length was at least six base pairs. This modification neither affected the association rate with target RNA nor the cleavage rate in vitro. In contrast to this, extension of helix II led to a significantly decreased inhibition of HIV-1 replication in human cells. Together with the finding of others that shortening of helix II to less than two base pairs reduces the catalytic activity in vitro, this observation indicates that the length of helix II in the naturally occurring RNAs with a hammerhead domain is already close or identical to the optimal length for catalytic activity in vitro and in vivo.
The autophagy machinery is required to initiate hepatitis C virus replication (2009)

In addition to its cellular homeostasis function, autophagy is emerging as a central component of antimicrobial host defense against diverse infections. To counteract this mechanism, many pathogens have evolved to evade, subvert, or exploit autophagy. Here, we report that autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but they are not required once infection is established. These results illustrate a previously unappreciated role for autophagy in the establishment of a viral infection and they suggest that different host factors regulate the translation of incoming viral genome and translation of progeny HCV RNA once replication is established.
Radiotherapy or surgery for head and neck squamous cell cancer (2009)

This study set the baseline for clinical decisions that was not previously established there is no difference in survival for patients with hypopharynx comparing primary surgery to primary radiotherapy. This information is essential for the interpretation of current treatment results, the planning of future clinical studies and the treatment of patients who are not having chemoradiotherapy.
Elevated level of serum growth differentiation factor 15 is associated with oral leukoplakia and oral squamous cell carcinoma (2013)

Elevated GDF15 level may be not only a diagnostic biomarker for oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC.
Transfection Techniques for Producing Recombinant Baculoviruses (2003)

The production of recombinant baculoviruses usually employs cotransfection of insect tissue-culture cells with viral and transfer-plasmid DNAs. The preparation and storage of viral and plasmid DNAs suitable for optimal transfection of insect cells are discussed. Electroporation, calcium-phosphate, and lipofection transfection techniques are presented with a discussion of their relative advantages. The rates of recombinant virus formation are compared using viral infection/plasmid transfection protocols versus cotransfection of cells with transfer-plasmid and viral DNAs.
Characterization of the polA Gene of Streptococcus pneumoniae and Comparison of the DNA Polymerase I It Encodes to Homologous Enzymes from Escherichia coli and Phage T7 (1989)

The DNA sequence of the polA gene of Streptococcus pneumoniae was determined, and the DNA polymerase I encoded by the gene was purified to homogeneity. Determination of the amino-terminal amino acid sequence of the protein showed it to correspond to the Mr 99,487 polypeptide predicted from the nucleotide sequence. The mRNA transcript was mapped with respect to its sites of initiation and termination in the DNA. Inasmuch as the mRNA begins only two nucleotides before the first codon, it lacks a typical ribosome binding site. Nevertheless, 500 molecules of the protein are produced per cell. Like the Escherichia coli DNA polymerase I, the protein from S. pneumoniae has 5'- and 3'-exonuclease as well as polymerase activities, and it also undergoes a single cleavage on mild proteolysis. Alignment of the two different polymerase I proteins shows 40% of their amino acid residues to be identical. Homology is evident also with the DNA polymerase encoded by phage T7 gene 5. In addition, the amino-terminal regions of the bacterial polymerase I proteins are homologous to the separate 5'-exonuclease protein encoded by phage T7 gene 6. Analysis of the patterns of homology suggests that the bacterial polymerase I may represent the accretion of at least six separate genetic regions.
[Ventilatory changes during laparoscopic cholecystectomy]. (1992)

During the past 2 years in Europe and the USA laparoscopic cholecystectomy (LC) has become a widely practiced procedure. Nevertheless, the effects of long-lasting laparoscopic procedures on carbon dioxide elimination have not yet been systematically investigated. METHODS. Approval from the institutional research review board was obtained, as was written informed consent from the patients. Eleven patients undergoing LC were studied. Patient age ranged from 31 to 67 years. All patients received total intravenous anaesthesia (fentanyl, propofol, vecuronium, DHB). Controlled ventilation with a tidal volume of 12-14 ml/kg was administered. Before introduction of anaesthesia a cannula was inserted into the left radial artery. Blood gas analysis was undertaken just before introduction, just before insufflation of carbon dioxide, and thereafter at two intervals, after reaching an intra-abdominal pressure of 12 mm Hg, 15 min apart. Oxygen consumption and carbon dioxide output were measured using a calorimeter (Deltatrac TM, Datex). Intra-abdominal pressure was maintained at 12 mm Hg during the operation. RESULTS. After onset of the pneumoperitoneum inspiratory peak and plateau pressure showed an increase by more than 40%. During the operation respiratory minute volume had to be increased by about 30-40% to maintain normocapnia. Oxygen consumption remained nearly unchanged during the procedure while carbon dioxide output increased up to 38% 60 min after onset of the pneumoperitoneum. D(a-A) CO2 showed no significant change, indicating no increase in dead space. Beginning with the insufflation there was a significant increase in mean arterial pressure that lasted until the end of the procedure. CONCLUSION. The described effects of carbon dioxide insufflation, especially the extent of carbon dioxide resorption, define the need for careful monitoring of respiratory function during LC, especially in patients with preexisting cardiopulmonary disease.
EFFECT OF LYSINE AND WETTING AGENTS ON ACTIVATED PLASMINOGEN SOLUTIONS (1963)

The inclusion of lysine or of lysine with Emulphor 620 or Pluronics F68 increases the stability of a solution of streptokinase-activated plasminogen. Lysine plus Emulphor 620 greatly speeds up the development of caseinolytic activity in a solution of Cohn fraction III-3. Proteolytic activity thus produced may, within 5 hours, equal that produced by streptokinase. Where lysine and Emulphor 620 are present in the reaction mixture between Cohn fraction III-3 and streptokinase, higher fibrinolytic values appear than are produced by the same quantity of reactants without Emulphor and lysine.
Frontal Lobe Syndrome in a Patient With Bilateral Globus Pallidus Lesions (1989)

This article describes a patient who experienced the rapid onset of an irreversible behavioral change while vacationing in La Paz, Bolivia (altitude, 4070 m). The only lesions demonstrated on a magnetic resonance imaging scan were bilateral hemorrhages in the globus pallidus. The behavior change was characterized by apathy and lack of motivation, features commonly associated with bilateral frontal lobe disease. This case is a further demonstration of how subcortical lesions can produce behavioral syndromes that are clinically indistinguishable from classic cortical syndromes. It is cases such as this that show how a strict localizationist concept of behavioral function is too restrictive and how it is necessary to consider a wide network of neuronal interconnections when explaining the mechanism of a dissolution of complex higher functions.
Growth factors activate the Na+/H+ antiporter in quiescent fibroblasts by increasing its affinity for intracellular H+. (1984)

Growth factors (alpha-thrombin and insulin) activate a Na+/H+ antiport in G0/G1-arrested Chinese hamster lung fibroblasts (CCL39). In this report, we have examined the influence of intracellular pH on this exchange activity, measured by initial rates of amiloride-sensitive 22Na+ uptake, in the absence and presence of growth factors. Our results indicate the following. 1) In quiescent as in mitogen-stimulated cells, Na+/H+ antiport is regulated by internal H+ in an allosteric way, whereas, in contrast, interactions with external H+ and Na+ obey simple saturation kinetics. 2) The growth factor-induced activation of Na+/H+ exchange, which, under physiological conditions, is responsible for a sustained cytoplasmic alkalinization, is due to an increased affinity for internal H+ (the apparent pK is shifted by approximately 0.3 pH unit towards alkaline pH values). Therefore, we propose that growth factors promote a conformational change of the Na+/H+ antiporter, possibly at the level of an internal modifier site(s).
Contribution of peptide backbone atoms to binding of an antigenic peptide to class I major histocompatibility complex molecule (1997)

Antigenic peptides are thought to bind to class I major histocompatibility complex (MHC) molecules through three modes of interaction: van der Waals interaction and, to a lesser extent, hydrogen bonding of anchor side chain atoms to residues comprising the binding pockets of the MHC molecule; hydrogen bonding of N- and C-termini to residues at the ends of the binding groove; and hydrogen bonding of peptide backbone atoms to residues lining the binding groove. To dissect the relative contribution of each of these interactions to class I MHC-peptide stability, a retro inverso (RI) analog of VSV-8. an H-2Kb restricted cytotoxic T lymphocyte (CTL) epitope and terminally modified variants of both VSV-8 and RI VSV-8 were synthesized and their ability to target H-2Kb bearing cells for CTL mediated lysis was compared. None of RI VSV-8 analogs elicited lysis of target cells by CTL specific for VSV-8 nor did they appear to compete with the native peptide for binding to H-2Kb. In contrast, terminally modified VSV-8 peptides elicited target lysis. These findings suggest that side chain topochemistry of the peptide is insufficient for stable peptide binding to H-2Kb; rather, hydrogen bonding of the peptide backbone atoms to H-2Kb side chain atoms appears to play a major role in the stability of the complex. Computer modeling confirmed that none of the RI analogs participate in the extensive hydrogen bonding network between the peptide backbone and the MHC molecule seen in the native structure.
Shake-Shake regularization (2017)

The method introduced in this paper aims at helping deep learning practitioners faced with an overfit problem. The idea is to replace, in a multi-branch network, the standard summation of parallel branches with a stochastic affine combination. Applied to 3-branch residual networks, shake-shake regularization improves on the best single shot published results on CIFAR-10 and CIFAR-100 by reaching test errors of 2.86% and 15.85%. Experiments on architectures without skip connections or Batch Normalization show encouraging results and open the door to a large set of applications. Code is available at https://github.com/xgastaldi/shake-shake
A distributed model for radiation-induced latchup (1988)

A lumped-model approach is used to determine three-dimensional effects that often dominate latchup behavior in complex integrated circuits. A preprocessor is used that automatically generates a SPICE-compatible file of up to several thousand elements from a basic description of the topology and physics of local structures. The results show that internal potential drops in the substrate and isolation wells are much larger than the metallization resistance contribution for devices with asymmetrical topology. The work also shows that alterations in the back contact, such as partial removal of the central portion for backside laser simulation, increase lateral voltage drops in the substrate by more than one order of magnitude, substantially changing the latchup characteristics. The model can be used to calculate distributed potentials that are important for latchup and the latchup window effect and to determine the effect of metal shadowing or nonuniform carrier generation when laser simulation is used.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MR‐trackable intramyocardial injection catheter (2004)

There is growing interest in delivering cellular agents to infarcted myocardium to prevent postinfarction left ventricular remodeling. MRI can be effectively used to differentiate infarcted from healthy myocardium. MR-guided delivery of cellular agents/therapeutics is appealing because the therapeutics can be precisely targeted to the desired location within the infarct. In this study, a steerable intramyocardial injection catheter that can be actively tracked under MRI was developed and tested. The components of the catheter were arranged to form a loopless RF antenna receiver coil that enabled active tracking. Feasibility studies were performed in canine and porcine myocardial infarction models. Myocardial delayed-enhancement (MDE) imaging identified the infarcted myocardium, and real-time MRI was used to guide left ventricular catheterization from a carotid artery approach. The distal 35 cm of the catheter was seen under MRI with a bright signal at the distal tip of the catheter. The catheter was steered into position, the distal tip was apposed against the infarct, the needle was advanced, and a bolus of MR contrast agent and tissue marker dye was injected intramyocardially, as confirmed by imaging and postmortem histology. A pilot study involving intramyocardial delivery of magnetically labeled stem cells demonstrated the utility of the active injection catheter system.
Beta-glucans in higher fungi and their health effects (2009)

Together with chitin, the beta-glucans are components of mycetes' cell walls. A high level of biological efficiency has been found in beta-glucans, especially beta-1,3-D-glucans and beta-1,6-D-glucans isolated from some basidiomycetes. (Biological efficiency refers to the relative ability of beta-glucans to promote a desired response, for example to induce leukocyte activation and to produce inflammatory mediators.) These polysaccharides increase the number of Th1 lymphocytes, which help protect organisms against allergic reactions. A number of beta-glucans, for example pleuran from Oyster (Pleurotus spp.) mushrooms or lentinan from Shiitake (Lentinus edodes) mushrooms, have shown marked anticarcinogenic activity. In addition to having an immunity-stimulating effect, beta-glucans may participate in physiological processes related to the metabolism of fats in the human body. Their application results in a decrease in the total cholesterol content in blood and may also contribute to reductions in body weight.
Context-sensitive filtering for the web (2003)

This paper proposes a filtering method on Web browsing. Some papers have reported that a user's interests shift continuously during browsing. To facilitate the user's browsing, a filtering system must adapt to the user's shift of interests. On the assumption that the user's interests are reflected in browsing page content and order, we have proposed Context-Sensitive Filtering (CSF) for a hypertext CD-ROM encyclopedia. In the encyclopedia, the entire hypertext is controlled to have one topic per page. We confirmed effectiveness of CSF for the encyclopedia. However, effectiveness of CSF for the Web was not confirmed. We inferred that the reason of failure is the difference in page properties of the Web and the encyclopedia. This paper describes modeling and CSF improvements. Main improvements include dividing a Web page to approximate an encyclopedia page and augmenting model calculation with TF-IDF. We confirmed effectiveness of proposed CSF through comparing several filtering methods.
Association of Obesity, Diabetes, Serum Lipids and Blood Pressure Regulates Insulin Action (2002)

Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg x m(-2), and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU x kg(-1) x min(-1) during 120 min. We evaluated the metabolic clearance rate of glucose (MCR(G), ml x kg(-1) x min(-1)) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCR(G): BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself.