gebhart/patrepeval huggingface dataset:
Exercise Capacity in Hypertrophic Cardiomyopathy (1995)

Background We previously showed that exercise capacity in patients with hypertrophic cardiomyopathy (HCM) is related to peak exercise cardiac output. Cardiac output augmentation during exercise is normally dependent on heart rate (HR) response and stroke volume (SV) augmentation by increased left ventricular end-diastolic volume and/or increased contractility. We hypothesized that in contrast to normal subjects, peak exercise capacity in patients with HCM is determined by the diastolic filling characteristics of the left ventricle during exercise, which would in turn determine the degree to which SV is augmented, and that HR is a relatively unimportant determinant of peak exercise capacity. Methods and Results Twenty-three patients with HCM underwent invasive hemodynamic evaluation and measurement of maximal oxygen consumption (V̇ o 2max ) during erect treadmill exercise to assess the relative importance of changes in HR and SV in determining exercise capacity. Hemodynamic responses to erect and supine exercise were compared in 10 of these patients. In a separate group of 46 patients with HCM, the relation between V̇ o 2max and exercise diastolic filling indexes was assessed. Peak HR during erect exercise was 92±8% of predicted maximum. V̇ o 2max was 29.0±6.4 mL · kg −1 · min −1 and was related significantly to peak exercise cardiac index and SV index ( r =.71, P &lt;.0001 and r =.66, P =.001, respectively) but not to peak HR, HR deficit, or resting or peak pulmonary capillary wedge pressure. Peak cardiac output during erect exercise was not related to peak HR ( r =.13, P =NS). When erect and supine exercise were compared, peak HR was lower in the supine position (153.3±19.9 beats per minute supine versus 172.0±17.6 beats per minute erect, P =.003), but peak exercise cardiac index was similar (7.9±2.6 L · min −1 · m −2 supine versus 7.5±2.8 L · min −1 · m −2 erect). Pulmonary capillary wedge pressure was higher at rest in the supine versus erect position (15.3±5.2 versus 8.1±6.1 mm Hg) but was not significantly higher at peak exercise in the supine versus erect position (28.5±8 versus 22.4±11.6 mm Hg erect, P =NS). In the separate group of 46 patients with HCM, V̇ o 2max was significantly inversely related to time to peak filling at peak exercise ( r =−.60, P &lt;.0001) but did not correlate with time to peak filling at rest, resting ejection fraction, peak filling rate, or peak exercise peak filling rate. Conclusions SV is the major determinant of peak exercise capacity in the erect position in patients with hypertrophic cardiomyopathy. This in turn is determined by the exercise left ventricular diastolic filling characteristics. HR augmentation does not appear to be a major determinant of peak cardiac output in the erect position.
Degradation Characteristics of a Novel PAF Receptor Antagonist, SY0916, in Aqueous Solution (2019)

SY0916 has been proven to be a potent treatment agent against rheumatoid arthritis in preclinical studies and has been shown to be safe in phase I clinical trials. However, SY0916 is unstable in water, which is frequently used in pharmaceutical development processes. The degradation behaviour and stability of SY0916 in aqueous solutions were investigated at different pH levels, periods of time, and temperatures. Two degradation products (DPs) were successfully separated and characterized by liquid chromatography coupled to high-resolution tandem mass spectrometry (LC-HRMS/MS), liquid chromatography coupled to nuclear magnetic resonance with solid phase extraction (LC-SPE-NMR), and nuclear magnetic resonance (NMR). SY0916 decomposed to its <i>α</i>,<i>β</i>-unsaturated ketone in protonic solvents, and the <i>α</i>,<i>β</i>-unsaturated ketone further transformed into its alcohol form through a conjugate addition reaction in aqueous media. The results of this study indicate that the pH of the buffer solutions should be maintained between 3.0 and 3.6 for maximum SY0916 stability. Factors that affect degradation should be carefully controlled to mitigate or avoid drug decay.
Detection of Early-Stage Pancreatic Adenocarcinoma (2010)

These results suggest the use of the PAM4 serum assay to detect early-stage pancreatic adenocarcinoma and that positive levels of PAM4 antigen are not derived from inflamed pancreatic tissues but rather may provide evidence of subclinical pancreatic neoplasia. EFFECT: The ability to detect pancreatic adenocarcinoma at an early stage could provide for early therapeutic intervention with potentially improved patient outcomes.
Sequence and glycosylation site identity of two distinct glycoforms of nonspecific cross-reacting antigen as demonstrated by sequence analysis and fast atom bombardment mass spectrometry. (1990)

Nonspecific cross-reacting antigen (NCA) is a highly glycosylated membrane protein which is immunologically and structurally related to carcinoembryonic antigen, an important tumor-associated antigen. Two glycoforms of NCA were purified from a single liver metastasis of a colonic carcinoma and characterized with respect to their primary sequence and position of glycosylation sites. The two glycoforms (designated TEX (tumor-extracted antigen), Mr 75,000, and NCA, Mr 45,000) each showed a deglycosylated Mr of 35,000 and yielded identical peptide maps. The structural characterization of TEX and NCA and the assignment of glycosylation sites was performed by fast atom bombardment mass spectrometry and microsequence analysis of the resulting peptides. This approach showed that TEX and NCA were identical with respect to primary sequence and provided direct evidence that 11 of the 12 predicted asparagine-linked glycosylation sites were glycosylated in both TEX and NCA. Indirect evidence was obtained for glycosylation at the other site. Both glycoforms also contain ethanolamine linked to Gly-286, a finding consistent with the conclusion that these proteins are anchored to the plasma membrane through a glycosyl-phosphatidylinositol tail. The large difference in the molecular weights of glycosylated TEX and NCA suggests significant variations in their oligosaccharide structures.
Data stream management system for MavHome (2004)

MavHome project provides rich applications for addressing various issues associated with stream data processing. In this paper, we present our approach for building a data stream management system (DSMS) for the above smart home project. We further summarize our primitive solutions for continuous query processing, Quality of Service(QoS) management, and mapping a trigger mechanism to a stream processing system.
Smoked cannabis for chronic neuropathic pain: a randomized controlled trial (2010)

A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).
Creating Alignment and Anisotropy in Engineered Heart Tissue: Role of Boundary Conditions in a Model Three-Dimensional Culture System (2003)

Electrical and mechanical anisotropy arise from matrix and cellular alignment in native myocardium. Generation of anisotropy in engineered heart tissue will be required to match native properties and will provide immediate opportunities to investigate the genesis and structural determinants of functional anisotropy. We investigated the influence of geometry and boundary conditions on fibroblast alignment in thin collagen gels. Consistent with previous reports, we found that human dermal fibroblasts align parallel to free edges in partially constrained gels; in contrast to at least one report, fibroblasts in fully constrained gels remained randomly aligned independent of geometry. These experiments allowed us to distinguish between two possible mechanisms for such alignment. Mean orientations that followed the shape of the free edges and stronger alignment nearest the free edges in gels with a variety of geometries suggested that cells align parallel to a local free boundary rather than to local lines of tension. These findings focus attention on the presence of voids and free surfaces such as the endocardium and epicardium, cleavage planes, and blood vessels in governing cell and fiber alignment in developing and remodeling myocardium, myocardial scar tissue, and engineered heart constructs.
Bioactive Isocoumarins and Related Metabolites from Conifer Endophytes (1995)

Six new [1-4, 7, 9] and two known [6 and 8] metabolites have been isolated from culture filtrates of conifer endophyte strains of Canoplea elegantula. Their structures have been determined by spectroscopic means. Compound 1 was toxic to spruce budworm cells, and both 1 and 3 were toxic to spruce budworm larvae.
Delineation of IL-5 domains predicted to engage the IL-5 receptor complex (1996)

IL-5 is an interdigitating homodimeric glycoprotein and a member of the helical bundle family of cytokines. IL-5 is a potent activator of eosinophils and a specific promoter of their differentiation. This activity has implicated IL-5 in the pathogenesis of asthma and allergic disease. A detailed understanding of IL-5 structure and function is required to develop immunomodulators of IL-5-mediated inflammatory responses. We generated a panel of neutralizing anti-IL-5 mAbs which were used to map functional domains on IL-5. In addition, the nucleotide sequences for human IL-5, murine IL-5, rat IL-5, and eight human/murine IL-5 chimeras were engineered and expressed in COS-7 cells. These recombinant cytokines and mAbs were used in TF-1 bioassays to identify five functional epitopes on the tertiary structure of IL-5. Residues responsible for the species-specific activity of human IL-5 were identified with the murine BCL1 bioassay. One set of epitopes cluster around the helix A-loop 2 region, which is predicted to engage the IL-5 receptor beta-chain. The second set of epitopes as well as the species specificity domain cluster around the loop 3-helix D region, which is predicted to engage the IL-5 receptor alpha-chain. Together, these analyses target the A/D helical face of IL-5 as the region involved in receptor engagement.
Generic Algorithm to Predict the Speed of Translational Elongation: Implications for Protein Biogenesis (2009)

Synonymous codon usage and variations in the level of isoaccepting tRNAs exert a powerful selective force on translation fidelity. We have developed an algorithm to evaluate the relative rate of translation which allows large-scale comparisons of the non-uniform translation rate on the protein biogenesis. Using the complete genomes of Escherichia coli and Bacillus subtilis we show that stretches of codons pairing to minor tRNAs form putative sites to locally attenuate translation; thereby the tendency is to cluster in near proximity whereas long contiguous stretches of slow-translating triplets are avoided. The presence of slow-translating segments positively correlates with the protein length irrespective of the protein abundance. The slow-translating clusters are predominantly located down-stream of the domain boundaries presumably to fine-tune translational accuracy with the folding fidelity of multidomain proteins. Translation attenuation patterns at highly structurally and functionally conserved domains are preserved across the species suggesting a concerted selective pressure on the codon selection and species-specific tRNA abundance in these regions.
Short Interfering RNA-Mediated Inhibition of Herpes Simplex Virus Type 1 Gene Expression and Function during Infection of Human Keratinocytes (2004)

RNA interference (RNAi) is an antiviral mechanism that is activated when double-stranded RNA is cleaved into fragments, called short interfering RNA (siRNA), that prime an inducible gene silencing enzyme complex. We applied RNAi against a herpes simplex virus type 1 (HSV-1) gene, glycoprotein E, which mediates cell-to-cell spread and immune evasion. In an in vitro model of infection, human keratinocytes were transfected with siRNA specific for glycoprotein E and then infected with wild-type HSV-1. RNAi-mediated gene silencing reproduced the small plaque phenotype of a gE-deletion mutant virus. The specificity of gene targeting was demonstrated by flow cytometry and Northern blot analyses. Exogenous siRNA can suppress HSV-1 glycoprotein E expression and function during active infection in vitro through RNAi. This work establishes RNAi as a genetic tool for the study of HSV and provides a foundation for development of RNAi as a novel antiviral therapy.
Doctor AI: Predicting Clinical Events via Recurrent Neural Networks (2015)

Leveraging large historical data in electronic health record (EHR), we developed Doctor AI, a generic predictive model that covers observed medical conditions and medication uses. Doctor AI is a temporal model using recurrent neural networks (RNN) and was developed and applied to longitudinal time stamped EHR data from 260K patients over 8 years. Encounter records (e.g. diagnosis codes, medication codes or procedure codes) were input to RNN to predict (all) the diagnosis and medication categories for a subsequent visit. Doctor AI assesses the history of patients to make multilabel predictions (one label for each diagnosis or medication category). Based on separate blind test set evaluation, Doctor AI can perform differential diagnosis with up to 79% recall@30, significantly higher than several baselines. Moreover, we demonstrate great generalizability of Doctor AI by adapting the resulting models from one institution to another without losing substantial accuracy.
Characterization of C4–2 Prostate Cancer Bone Metastases and Their Response to Castration (2003)

The C4-2 model of bone metastasis recapitulates the response to androgen deprivation observed in CaP patients with bone metastases and is suitable for study of interactions between tumor and bone cells and evaluation of new therapeutic modalities.
Significant temperature and pressure sensitivities of electrical properties in chemically modified multiwall carbon nanotube/methylvinyl silicone rubber nanocomposites (2006)

The effects of γ-aminopropyltriethoxy silane coupling agent on electrical properties in multiwall carbon nanotube/methylvinyl silicone rubber nanocomposites were studied. The results showed that the modified nanotubes could be dispersed homogeneously and that they had a tight bonding with the rubber matrix. The concentration of coupling agent played a crucial role in deciding the conductivity and the electrical properties of the nanocomposites exhibited strong dependences on temperature and pressure. Dependences of electrical properties on temperature and pressure were also improved by increasing the content of coupling agent.
Sesquiterpenes as Phytoalexins and Allelopathic Agents (1987)

The plant origin and structure are given for those sesquiterpenes which have been shown to be active as phytoalexins or allelopathic agents. Potato (Solanum tuberosum), pepper (Capsicum annum), tobacco (Nicotiana species), eggplant (Solanum melongena), tomato (Lycopersicon esculentum) and jimsonweed (Datura stramonium), all members of the Solanaceae, are rich sources of sesquiterpenoid phytoalexins. Over twenty furanosesquiterpenoid phytoalexins have been isolated from sweet potato (Ipomoea batatus). Both elm (Ulmus glabra) and cotton (Gossypium species) have also been sources of sesquiterpenoid phytoalexins. Allelopathic sequiterpenoids have been implicated in a limited number of investigations. Potential sesquiterpenoid allelochemicals have been found in Artemisia absenthium, Ambrosia psilostachya, Cyperus serotinus and Lippia nodiflora.
A Genetic Screen to Identify Bacteriophage Lysins (2009)

Lysins are phage-encoded, peptidoglycan (cell wall) hydrolases that accumulate in the bacterial cytoplasm during a lytic infection cycle. Late during infection, the lysins undergo holin-mediated translocation across the inner membrane into the peptidoglycan matrix where they cleave cell wall covalent bonds required for wall stability and allow bacterial lysis and progeny phage release. This potent hydrolytic activity is now the foundation of a powerful genetic-based screening process for the identification and analysis of phage lysin proteins. Here, we describe a method for identifying a lysin, PlyG, from a bacteriophage that specifically infects the Gram-positive organism Bacillus anthracis; however, the techniques described can be adapted to clone, express, and analyze lysins from any phage infecting Gram-positive bacteria or possibly even Gram-negative bacteria.
Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation (2004)

The 1,3-dipolar cycloaddition reaction between unactivated azides and acetylenes proceeds exceedingly slowly at room temperature. However, considerable rate acceleration is observed when this reaction occurs inside the active center gorge of acetylcholinesterase (AChE) between certain azide and acetylene reactants, attached via methylene chains to specific inhibitor moieties selective for the active center and peripheral site of the enzyme. AChE catalyzes the formation of its own inhibitor in a highly selective fashion: only a single syn1-triazole regioisomer with defined substitution positions and linker distances is generated from a series of reagent combinations. Inhibition measurements revealed this syn1-triazole isomer to be the highest affinity reversible organic inhibitor of AChE with association rate constants near the diffusion limit. The corresponding anti1 isomer, not formed by the enzyme, proved to be a respectable but weaker inhibitor. The crystal structures of the syn1- and anti1-mouse AChE complexes at 2.45- to 2.65-A resolution reveal not only substantial binding contributions from the triazole moieties, but also that binding of the syn1 isomer induces large and unprecedented enzyme conformational changes not observed in the anti1 complex nor predicted from structures of the apoenzyme and complexes with the precursor reactants. Hence, the freeze-frame reaction offers both a strategically original approach for drug discovery and a means for kinetically controlled capture, as a high-affinity complex between the enzyme and its self-created inhibitor, of a highly reactive minor abundance conformer of a fluctuating protein template.
Atomic garbage collection: managing a stable heap (1989)

Modern database systems use transactions to achieve a high degree of fault-tolerance. Many modern programming languages and systems provide garbage collected heap storage, which frees the programmer from the job of explicitly deallocating storage. In this paper we describe integrated garbage collection and recovery algorithms for managing a stable heap in which accessible objects survive both system crashes and media failures. A garbage collector typically both moves and modifies objects which can lead to problems when the heap is stable because a system crash after the start of collection but before enough of the reorganized heap reaches the disk can leave the disk in an inconsistent state. Furthermore, collection has to be coordinated with the recovery system. We present a collection algorithm and recovery system that solves these problems.
Phosphopeptides interacting with colloidal calcium phosphate isolated by tryptic hydrolysis of bovine casein micelles (1996)

After extended tryptic hydrolysis of large bovine casein micelles, a mineral-rich peptide fraction was recovered by ultracentrifugation. Its mineral part contained 72% of the colloidal Ca and 49% of the colloidal P1 originally present in the native micelle. Colloidal nitrogenous components were also present, amounting to 27% of the original N content. They contained most of the phosphopeptides and 82% of the micellar phosphoseryl residues. These tryptic peptides were characterized by reversed-phase HPLC on-line electrospray ion source-mass spectrometry analysis. Among the peptides produced 14 phosphopeptides were identified: alpha s2-CN(1-24), alpha s2-CN(1-21), alpha s1-CN(43-79), alpha s1-CN(35-79)7P, alpha s1-CN(35-79)8P, alpha s1-CN(37-79), alpha s1-CN(104-119), alpha s1-CN(104-124), beta-CN(1-25), beta-CN(1-28), beta-CN(1-29), beta-CN(30-97), beta-CN(33-97) and beta-CN(29-97). The proportion of the phosphopeptides interacting with colloidal calcium phosphate was correlated with their relative content of phosphoserine residues, since phosphopeptides containing more than four phosphoserine residues were consistently present within this fraction. It also appeared that other types of peptides, some of them hydrophobic in nature, were also partly or completely present within the colloidal fraction, including alpha s1-CN(91-100), alpha s1-CN(152-193), alpha s1-CN(23-34), alpha s1-CN(125-193), alpha s1-CN(125-199), beta-CN(177-209). beta-CN(184-209), beta-CN(114-169) and beta-CN(108-169). Their possible involvement in the micellar backbone is discussed.
Phagocytosis and the microtubule cytoskeleton (2002)

Phagocytosis is a critical host defense mechanism used by macrophages and neutrophils to clear invading pathogens. The complex sequence of events resulting in internalization and degradation of the pathogens is a coordinated process involving lipids, signaling proteins, and the cytoskeleton. Here, we examine the role of the microtubule cytoskeleton in supporting both the engulfment of pathogens and their elimination within phagolysosomes.
Activation of human factor V by factor Xa and thrombin (1990)

The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by either autoradiography of 125I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of Mr 220,000 and 105,000. Although thrombin cleaved the Mr 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the Mr 220,000 peptide. The factor Xa dependent functional assessment of 125I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the Mr 220,000 peptide. This observation facilitated the study of the kinetics of factor V activation by allowing the activation of factor V to be monitored by the appearance of the Mr 220,000 peptide (factor Xa activation) or the Mr 105,000 peptide (thrombin activation). Factor Xa catalyzed activation of factor V obeyed Michaelis-Menten kinetics and was characterized by a Km of 10.4 nM, a kcat of 2.6 min-1, and a catalytic efficiency (kcat/Km) of 4.14 X 10(6) M-1 s-1. The thrombin-catalyzed activation of factor V was characterized by a Km of 71.7 nM, a kcat of 14.0 min-1, and a catalytic efficiency of 3.26 X 10(6) M-1 s-1. This indicates that factor Xa is as efficient an enzyme toward factor V as thrombin.