gebhart/patrepeval huggingface dataset:
The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis (1999)

Heme oxygenase is the rate limiting enzyme in heme degradation to carbon monoxide (CO), iron and bilirubin. The inducible isoform of the protein, heme oxygenase-1 (HO-1), is susceptible to up-regulation by a diverse variety of conditions and agents in mammalian tissue, leading to the common conception that HO-1 is a stress related enzyme. However, as attempts are made to unravel the mechanisms by which HO-1 is induced and as we discover that CO, iron and bilirubin may be important effector molecules, we are learning to appreciate that heme oxygenases may be central to the regulation of many physiological and pathophysiological processes besides their established function in heme catabolism. One such process may be closely linked to nitric oxide (NO). It has been demonstrated that NO and NO donors are capable of inducing HO-1 protein expression, in a mechanism depending on the de novo synthesis of RNA and protein. Thus, it is postulated that NO may serve as a signaling molecule in the modulation of the tissue stress response. This review will highlight the current ideas on the role of CO-heme oxygenase and NO-nitric oxide synthase in cell signaling and discuss how the two systems are interrelated.
DeepAtom: A Framework for Protein-Ligand Binding Affinity Prediction (2019)

The cornerstone of computational drug design is the calculation of binding affinity between two biological counterparts, especially a chemical compound, i.e., a ligand, and a protein. Predicting the strength of protein-ligand binding with reasonable accuracy is critical for drug discovery. In this paper, we propose a data-driven framework named DeepAtom to accurately predict the protein-ligand binding affinity. With 3D Convolutional Neural Network (3D-CNN) architecture, DeepAtom could automatically extract binding related atomic interaction patterns from the voxelized complex structure. Compared with the other CNN based approaches, our light-weight model design effectively improves the model representational capacity, even with the limited available training data. With validation experiments on the PDBbind v.2016 benchmark and the independent Astex Diverse Set, we demonstrate that the less feature engineering dependent DeepAtom approach consistently outperforms the other state-of-the-art scoring methods. We also compile and propose a new benchmark dataset to further improve the model performances. With the new dataset as training input, DeepAtom achieves Pearson's R=0.83 and RMSE=1.23 pK units on the PDBbind v.2016 core set. The promising results demonstrate that DeepAtom models can be potentially adopted in computational drug development protocols such as molecular docking and virtual screening.
Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses (2012)

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.
Immunodominant mink cell focus-inducing murine leukemia virus (MuLV)-encoded CTL epitope, identified by its MHC class I-binding motif, explains MuLV-type specificity of MCF-directed cytotoxic T lymphocytes. (1994)

H-2b mice are immunologic responders to the tumorigenic MCF1233 murine leukemia virus (MuLV), an AKV-related virus derived from endogenous C57BL MuLV. We have identified an immunodominant CTL epitope that is expressed on MCF1233 MuLV-induced lymphomas of H-2b mice. C57BL/10 (B10) mice were immunized with an MCF1233-induced B10 B cell lymphoma, and tumor-specific CTL cultures were generated in vitro. These were tested for recognition of synthetic class I-binding MuLV peptides, selected for class I allele-specific motifs. One of 28 candidate peptides sensitized target cells for CTL recognition. This peptide seems to be an immuno-dominant epitope, because it was recognized by all independent CTL clones, isolated from the tumor-specific bulk culture. The epitope (KSPWFTTL) is derived from the MCF1233 MuLV envelope (env)-p15E region and is shared by all endogenous AKV types of MuLV. It has an optimal length of eight amino acids and is presented by the Kb H-2 class I molecule. Interestingly, Friend, Moloney, and Rauscher (FMR) types of MuLV are not recognized by MCF MuLV-directed CTL. The FMR env-p15E proteins have a single amino acid difference at the first position of the MCF1233 MuLV epitope (RSPWFTTL instead of KSPWFTTL). The corresponding FMR-encoded peptide bound class I H-2 Kb equally well as the MCF peptide, but it was poorly recognized by MCF1233 MuLV-specific CTL. Moreover, in the Rauscher MuLV-induced cell line RMA the FMr peptide seems not to be processed for recognition by CTL, which was illustrated by experiments with CTL elicited against this peptide. Altered TCR interaction as well as lack of processing thus may explain the type specificity of MCF1233 MuLV-directed CTL.
Fluticasone Furoate, a Novel Inhaled Corticosteroid, Demonstrates Prolonged Lung Absorption Kinetics in Man Compared with Inhaled Fluticasone Propionate (2012)

In comparison with inhaled FP, inhaled FF (independent of formulation) demonstrated prolonged absorption from the lung into the systemic circulation, indicating a longer lung retention time and suggesting the potential for maintained efficacy with once-daily administration.
Paired states of fermions in two dimensions with breaking of parity and time-reversal symmetries and the fractional quantum Hall effect (2000)

We analyze pairing of fermions in two dimensions for fully gapped cases with broken parity (P) and time reversal (T), especially cases in which the gap function is an orbital angular momentum (l) eigenstate, in particular $l=\ensuremath{-}1$ (p wave, spinless, or spin triplet) and $l=\ensuremath{-}2$ (d wave, spin singlet). For $l\ensuremath{\ne}0,$ these fall into two phases, weak and strong pairing, which may be distinguished topologically. In the cases with conserved spin, we derive explicitly the Hall conductivity for spin as the corresponding topological invariant. For the spinless p-wave case, the weak-pairing phase has a pair wave function that is asympototically the same as that in the Moore-Read (Pfaffian) quantum Hall state, and we argue that its other properties (edge states, quasihole, and toroidal ground states) are also the same, indicating that nonabelian statistics is a generic property of such a paired phase. The strong-pairing phase is an abelian state, and the transition between the two phases involves a bulk Majorana fermion, the mass of which changes sign at the transition. For the d-wave case, we argue that the Haldane-Rezayi state is not the generic behavior of a phase but describes the asymptotics at the critical point between weak and strong pairing, and has gapless fermion excitations in the bulk. In this case the weak-pairing phase is an abelian phase, which has been considered previously. In the p-wave case with an unbroken $U(1)$ symmetry, which can be applied to the double layer quantum Hall problem, the weak-pairing phase has the properties of the 331 state, and with nonzero tunneling there is a transition to the Moore-Read phase. The effects of disorder on noninteracting quasiparticles are considered. The gapped phases survive, but there is an intermediate thermally conducting phase in the spinless p-wave case, in which the quasiparticles are extended.
Interleukin 1α Increases Serum Leptin Concentrations in Humans (1997)

Leptin, the protein product of the ob gene, regulates appetite and body weight in animals. Endotoxin and cytokines, induced by endotoxin, interleukin (IL) 1 and tumor necrosis factor, increase expression of leptin in mice and hamsters. We measured serum leptin concentrations in patients with cancer before and after administration of recombinant human IL-1 alpha. Fourteen patients received IL-1 alpha at one of three dose levels (0.03, 0.1, or 0.3 microgram/kg.day) for 5 days. Serum leptin concentrations increased in all but two patients within 24 h after the first dose. The increase in leptin was correlated directly with IL-1 alpha dose (P = 0.0030). Despite continued administration of IL-1 alpha, serum leptin concentrations returned to pretreatment levels by day 5 of therapy. An increase in serum leptin concentrations may be one mechanism by which anorexia is induced by IL-1 alpha. However, tachyphylaxis of the leptin response suggests that other mechanisms also are involved.
Glucagon in Heart Failure and in Cardiogenic Shock (1972)

Intravenous glucagon, in doses of 2.5-15 mg/hour, was administered to 50 patients for periods of 1-7 days. Forty patients had either intractable heart failure or cardiogenic shock or both; the remaining 10 had less severe heart disease. In all patients glucagon was added to conventional therapy. Twenty-two of the 40 with very severe heart failure showed a clinical improvement, and 18 were discharged from the hospital; 16 of the 18 patients who did not respond died in the hospital. Only two of the 10 with less severe heart disease improved with glucagon but all could be discharged from the hospital. Glucagon did not initiate or aggravate a tendency to arrhythmias in any of the 17 patients with acute myocardial infarction. In two patients with bradycardia and cardiac failure due to beta-adrenergic blocking drugs, glucagon increased heart rate and there was clinical improvement in heart failure. However, there was no effect in two patients with digitalis-induced nodal bradycardia and heart failure. Nausea was the most troublesome side effect and this could usually be controlled by intramuscular prochlorperazine (Stemetil) which was given routinely before the infusion in all except postoperative patients and repeated as required during the infusion. The results show that glucagon has a definite place in the management of patients with severe heart failure when used as an adjunct to conventional therapy.
Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury (2007)

We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.
Organ distribution and toxicity of lignin. (1999)

It is suggested that 125I-labeled natural and synthetic lignins administered orally to mice are absorbed through the digestive tract and excreted via urine, in addition to feces. Intravenous administration of lignins produced preferential accumulation of radioactivity in the liver and also in the stomach tissue and lung. It also induced an increase in the spleen weight (splenomegaly), suggesting that the immune system might be stimulated. Lignin significantly increased the heme oxygenase among several hepatic enzymes. Macroscopical examination of mice which were administered a lethal dose of lignin showed nasal and lung congestion leading to hemorrhage.
Bayesian Q-learning (1998)

A central problem in learning in complex environments is balancing exploration of untested actions against exploitation of actions that are known to be good. The benefit of exploration can be estimated using the classical notion of Value of Information ---the expected improvement in future decision quality that might arise from the information acquired by exploration. Estimating this quantity requires an assessment of the agent&amp;apos;s uncertainty about its current value estimates for states. In this paper, we adopt a Bayesian approach to maintaining this uncertain information. We extend Watkins&amp;apos; Q-learning by maintaining and propagating probability distributions over the Q-values. These distributions are used to compute a myopic approximation to the value of information for each action and hence to select the action that best balances exploration and exploitation. We establish the convergence properties of our algorithm and show experimentally that it can exhibit substantial improvements o...
A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non–Small Cell Lung Cancer (2010)

PD-0325901 did not meet its primary efficacy end point. Future studies should focus on PD-0325901 schedule, rational combination strategies, and enrichment of patient selection based on mode of action.
Escherichia coli contains a soluble ATP-dependent protease (Ti) distinct from protease La. (1987)

The energy requirement for protein breakdown in Escherichia coli has generally been attributed to the ATP-dependence of protease La, the lon gene product. We have partially purified another ATP-dependent protease from lon-cells that lack protease La (as shown by immunoblotting). This enzyme hydrolyzes [3H]methyl-casein to acid-soluble products in the presence of ATP and Mg2+. ATP hydrolysis appears necessary for proteolytic activity. Since this enzyme is inhibited by diisopropyl fluorophosphate, it appears to be a serine protease, but it also contains essential thiol residues. We propose to name this enzyme protease Ti. It differs from protease La in nucleotide specificity, inhibitor sensitivity, and subunit composition. On gel filtration, protease Ti has an apparent molecular weight of 370,000. It can be fractionated by phosphocellulose chromatography or by DEAE chromatography into two components with apparent molecular weights of 260,000 and 140,000. When separated, they do not show proteolytic activity. One of these components, by itself, has ATPase activity and is labile in the absence of ATP. The other contains the diisopropyl fluorophosphate-sensitive proteolytic site. These results and the similar findings of Katayama-Fujimura et al. [Katayama-Fujimura, Y., Gottesman, S. & Maurizi, M. R. (1987) J. Biol. Chem. 262, 4477-4485] indicate that E. coli contains two ATP-hydrolyzing proteases, which differ in many biochemical features and probably in their physiological roles.
Grating efficiency theory as it applies to blazed and holographic gratings (1977)

Recently developed rigorous theories have been used to investigate the diffraction efficiency behavior of both blazed and holographic gratings. In order to assist designers of spectrometric systems we have covered a complete range of blaze angles for triangular grooves and modulations for sinusoidal groove shape in first and second orders. Several types of mountings are included together with the role played by finite conductivity of aluminum. Useful classifications of both types of gratings are given, as they apply from the near uv to ir regions. Comparisons showing the close agreement between theory and experiment are presented.
Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens (1997)

It is well known that Giardia lamblia and Cryptosporidium parvum can cause severe symptoms in humans, particularly those who are immunologically compromised. Immunoassay procedures offer both increased sensitivity and specificity compared to conventional staining methods. These reagents are also helpful when screening large numbers of patients, particularly in an outbreak situation or when screening patients with minimal symptoms. The data obtained by using 9 diagnostic kits were compared: direct fluorescent-antibody assay (DFA) kits (TechLab Giardia/Crypto IF kit, TechLab Crypto IF kit, and Meridian Merifluor Cryptosporidium/Giardia) and enzyme immunoassay (EIA) kits (Alexon ProSpecT Giardia EZ Microplate Assay, Alexon ProSpecT Cryptosporidium Microplate Assay, Cambridge Giardia lamblia Antigen Microwell ELISA, Meridian Premier Giardia lamblia, Meridian Premier Cryptosporidium, TechLab Giardia CELISA, Trend Giardia lamblia EIA). The test with the Meridian Merifluor Cryptosporidium/Giardia kit was used as the reference method. In various combinations, 60 specimens positive for Giardia, 60 specimens positive for Cryptosporidium, 40 specimens positive for a Giardia-Cryptosporidium mix, and 50 negative fecal specimens were tested. Different species (nine protozoa, three coccidia, one microsporidium, five nematodes, three cestodes, and one trematode) were included in the negative specimens. The sensitivity of EIA for Giardia ranged from 94% (Alexon) to 99% (Trend and Cambridge); the specificity was 100% with all EIA kits tested. The sensitivity of EIA for Cryptosporidium ranged from 98% (Alexon) to 99% (Meridian Premier); specificities were 100%. All DFA results were in agreement, with 100% sensitivity and specificity; however, the TechLab reagents resulted in fluorescence intensity that was generally one level below that seen with the reagents used in the reference method. In addition to sensitivity and specificity, factors such as cost, simplicity, ease of interpretation of results (color, intensity of fluorescence), equipment, available personnel, and number of tests ordered are also important considerations prior to kit selection.
Molecular variation in the major outer membrane protein P5 gene of nonencapsulated Haemophilus influenzae during chronic infections (1997)

During the course of persistent infections by nonencapsulated Haemophilus influenzae in patients with chronic bronchitis, the major outer membrane protein (MOMP) P5 varies in molecular weight. The nature of this variability was determined by DNA sequence analysis of the P5 gene from five different H. influenzae strains and their seven MOMP P5 variants which were isolated from patients with chronic infections of the lower respiratory tract. Analysis of the P5 sequence data from the different strains revealed four well-defined, heterogeneous regions. These regions of variable sequence appeared to correspond to the regions of the gene encoding the putative surface-exposed loops of MOMP P5. The MOMP P5 variants with alterations in MOMP P5 were shown to result from DNA point mutations and codon deletions. In addition, in three variants derived sequentially from one H. influenzae strain, a frameshift mutation resulted in the formation of a stop codon in the region encoding the signal sequence of the MOMP P5 gene. Strikingly, all nucleotide substitutions in the MOMP P5 loop regions of variants were nonsynonymous, suggesting that variants with alterated amino acid compositions of the surface-exposed parts of MOMP P5 obtained a selective advantage during persistence of the infection by nonencapsulated H. influenzae in chronic bronchitis patients.
Targeting multiple pathways in gliomas with stem cell and viral delivered S-TRAIL and Temozolomide (2008)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells. However, its short half-life, poor delivery, and TRAIL-resistant tumor cells have diminished its clinical efficacy. In this study, we explored whether novel delivery methods will represent new and effective ways to treat gliomas and if adjuvant therapy with the chemotherapeutic agent temozolomide would enhance the cytotoxic properties of TRAIL in glioma lines resistant to TRAIL monotherapy. We have engineered adeno-associated virus (AAV) vectors encoding recombinant secreted TRAIL (S-TRAIL) and bioluminescent-fluorescent marker fusion proteins and show that AAV-delivered S-TRAIL leads to varying degrees of killing in multiple glioma lines, which correspond with caspase-3/7 activation. In vivo, dual bioluminescent imaging revealed efficient delivery of therapeutic AAV vectors directly into the tumor mass, which induced marked attenuation of tumor progression. Treatment of glioma cells with the chemotherapeutic agent temozolomide alone lead to a significant accumulation of cells in G(2)-M phase, activated the cell cycle checkpoint protein Chk1, and increased death receptor expression in a time-dependent manner. Furthermore, combined treatment with AAV-S-TRAIL or neural stem cell-S-TRAIL and temozolomide induced cell killing and markedly up-regulated proapoptotic proteins in glioma cells least sensitive to TRAIL. This study elucidates novel means of delivering S-TRAIL to gliomas and suggests combination of clinically relevant temozolomide and S-TRAIL may represent a new therapeutic option with increased potency for glioblastoma patients.
A calculus for overloaded functions with subtyping, extended abstract (1992)

We present a simple extension of typed -calculus where functions can be overloaded by adding different &amp;quot;pieces of code&amp;quot;. In short, the code of an overloaded function is formed by several branches of code; the branch to execute is chosen, when the function is applied, according to a particular selection rule which depends on the type of the argument. The crucial feature of the present approach is that a subtyping relation is defined among types, such that the type of a term generally decreases during computation, and this fact induces a distinction between the &amp;quot;compile-time&amp;quot; type and the &amp;quot;run-time&amp;quot; type of a term. We study the case of overloaded functions where the branch selection depends on the run-time type of the argument, so that overloading cannot be eliminated by a static analysis of code, but is an essential feature to be dealt with during computation. We obtain in this way a type-dependent calculus, which differs from the various \\Gammacalculi where types do not play, essenti...
La aldea de El Rocío y sus «confines» (2018)

espanolHacemos en este articulo un recorrido por toda la cartografia relativa al lugar de El Rocio en Almonte, provincia de Huelva, desde el siglo XVI hasta el siglo XIX, para obtener un estudio de sus confines, apoyado en las fuentes historicas y documentales que han descrito sus limites a lo largo del tiempo. EnglishIn this article we explore all of the cartography related to El Rocio in Almonte, the province of Huelva, from the 16th to the 19th century in order to study its confines, based on historical and documental references that traced the municipal limits over time.
Outcome, timing and adverse events in therapeutic hypothermia after out‐of‐hospital cardiac arrest (2009)

Half of the patients survived, with >90% having a good neurological function at long-term follow-up. Factors related to the timing of TH had no apparent association to outcome. The incidence of adverse events was acceptable but the risk of bleeding was increased if angiography/PCI was performed.