gebhart/patrepeval huggingface dataset:
Isolation of a porcine respiratory, non‐enteric coronavirus related to transmissible gastroenteritis (1986)

A porcine respiratory, non-enteric virus which is related to the coronavirus transmissible gastroenteritis virus (TGEV) has been isolated in pigs and in cell culture. The isolate was designated TLM 83. It has become very widespread and enzootic among the swine population in Belgium and in other swine raising countries. It causes an infection of the lungs and appears to spread by aerogenic route. It does not replicate in the enteric tract. The experimental infection in conventional and gnotobiotic pigs in isolation remains subclinical. The infection, either experimental or in the field, results in the formation of antibodies which neutralise the classical enteric TGEV. Based on this relationship, this virus is assumed to be a new TGEV-related porcine respiratory coronavirus or TGEV itself which has totally lost its tropism for the enteric tract.
Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial (2004)

A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.
Litigation in Nontraumatic Aortic Diseases – A Tempest in the Malpractice Maelstrom (2007)

Aortic disease can be diagnostically elusive, as 'the great masquerader'. Emergency physicians must maintain a high index of suspicion for aneurysm and dissection. The D-dimer test can effectively rule out aortic dissection. 'Triple rule-out' CT scans should be performed liberally. CT scan readers must remember to evaluate the aorta. Operating room administrators must be aware that postponing a scheduled thoracic aortic case may result in interim rupture and consequent litigation. With virulent thoracic aortic diseases, adverse outcome itself does not imply substandard care.
Dynamic Modeling and Control of DFIG-Based Wind Turbines Under Unbalanced Network Conditions (2007)

This paper presents an analysis and control design of a doubly-fed induction generator (DFIG)-based wind generation system operating under unbalanced network conditions. A DFIG system model in the positive and negative synchronous reference frames is presented. Variations of stator active and reactive powers and generator torque are fully defined in the presence of negative sequence voltage and current. Alternative DFIG control targets during network unbalance, such as reducing stator current unbalance, torque, and power pulsations minimization, are identified. A rotor current control strategy based on positive and negative (dq) reference frames is used to provide precise control of the rotor positive and negative sequence currents. Simulation results using EMTDC/PSCAD are presented for a 2-MW DFIG wind generation system. It shows that conventional vector control of DFIG without considering network unbalance results in excessive oscillations on the stator active/reactive power, electromagnetic torque, and stator/rotor currents even with a small stator voltage unbalance. In contrast, with the proposed control strategy, enhanced system control and operation such as minimizing oscillations in either active power, or electromagnetic torque, or stator or rotor currents can be achieved
Architecture of scalable backup service for private cloud (2013)

In this paper we propose a scalable backup service for virtualization infrastructure such as private cloud called hBaaS. hBaaS is designed to utilize existing infrastructure without the needs of additional equipment to provision it as-a-Service model. We propose an integrated solution for virtualization platform that scales as the total VMs increases. The solution addresses the issue of concentrated backup schedule on a specific time range which potentially cause resource bottleneck. We discuss two methods to reduce the backup workload footprint; by distributing the backup workload operation into multiple proxy servers and push the backup operations into background which increases the duration of time to backup but lessen the impact of backup operation to the infrastructure. Indirectly, hBaaS will be able to cater more backup requests from users.
Biological actions of brain natriuretic peptide in thoracic inferior vena caval constriction (1993)

Brain natriuretic peptide (BNP) shares structural and functional similarities to atrial natriuretic peptide (ANP). Although BNP and ANP interact with the same biologically active guanylate cyclase-coupled receptor, recent reports conflict with regard to the biological actions of exogenous BNP in sodium-retaining and edematous states. We studied the biological actions of BNP in normal dogs (n = 5) and sodium-avid dogs with chronic thoracic inferior vena caval constriction (TIVCC) (n = 6). In normal dogs BNP increased glomerular filtration rate, renal blood flow, and urinary sodium excretion and decreased proximal and distal fractional reabsorption of sodium with activation of urinary guanosine 3',5'-cyclic monophosphate (cGMP). These renal actions occurred in association with marked hypotensive actions and activation of systemic cGMP. In TIVCC, a state characterized by chronic reductions of cardiac output, avid sodium retention, edema, and activation of the renin-angiotensin-aldosterone system (RAAS), the renal actions of BNP were absent in association with marked attenuation of the urinary cGMP response. In contrast, an enhanced hypotensive response with preserved activation of systemic cGMP was observed. In neither normal dogs nor TIVCC dogs did BNP inhibit the RAAS. These studies report that BNP is a potent vasoactive and natriuretic peptide with potent proximal and distal tubular actions in normal dogs. These studies also demonstrate that in TIVCC, a model of low cardiac output and congestive failure that results in marked sodium retention with edema in which there is activation of the RAAS, the renal actions of BNP are attenuated while the vasoactive actions are enhanced.
Understanding organofluorine chemistry. An introduction to the C–F bond (2007)

Fluorine is the most electronegative element in the periodic table. When bound to carbon it forms the strongest bonds in organic chemistry and this makes fluorine substitution attractive for the development of pharmaceuticals and a wide range of speciality materials. Although highly polarised, the C-F bond gains stability from the resultant electrostatic attraction between the polarised C delta+ and F delta- atoms. This polarity suppresses lone pair donation from fluorine and in general fluorine is a weak coordinator. However, the C-F bond has interesting properties which can be understood either in terms of electrostatic/dipole interactions or by considering stereoelectronic interactions with neighbouring bonds or lone pairs. In this tutorial review these fundamental aspects of the C-F bond are explored to rationalise the geometry, conformation and reactivity of individual organofluorine compounds.
Effect of Polyethyleneglycol (PEG) Chain on Cell Uptake of PEG-Modified Liposomes (2003)

The liposomalization and polyethyleneglycol (PEG) modification of antitumor agents prolongs their circulation in the blood and increases their accumulation in the tumor. It is expected that modification of the liposome surface with PEG-Lipid will prevent connection of liposome and tumor cell, so we examined the effect of PEG chain length and anchor length on liposome uptake into the tumor cell. It was obvious that modification of the liposome surface with PEG-Lipid did not prevent liposome uptake into tumor cells, but rather, promoted it. It was suggested that the increase in liposome uptake into the tumor cell was induced by modification of PEG-lipids with apparent stability. In other words, PEG 2,000-DPG, which had a high rate of residual PEG-Lipid on liposomal membrane depending on the re-uptake to liposomal membrane, met to this requirement.
Direct one-step conversion of alcohols into nitriles (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDirect one-step conversion of alcohols into nitrilesRoman Davis and Karl G. UntchCite this: J. Org. Chem. 1981, 46, 14, 2985–2987Publication Date (Print):July 1, 1981Publication History Published online1 May 2002Published inissue 1 July 1981https://pubs.acs.org/doi/10.1021/jo00327a034https://doi.org/10.1021/jo00327a034research-articleACS PublicationsRequest reuse permissionsArticle Views2093Altmetric-Citations54LEARN 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
Is There a Difference between Leads and Drugs? A Historical Perspective (2001)

To be considered for further development, lead structures should display the following properties: (1) simple chemical features, amenable for chemistry optimization; (2) membership to an established SAR series; (3) favorable patent situation; and (4) good absorption, distribution, metabolism, and excretion (ADME) properties. There are two distinct categories of leads: those that lack any therapeutic use (i.e., "pure" leads), and those that are marketed drugs themselves but have been altered to yield novel drugs. We have previously analyzed the design of leadlike combinatorial libraries starting from 18 lead and drug pairs of structures (S. J. Teague et al. Angew. Chem., Int. Ed. Engl. 1999, 38, 3743-3748). Here, we report results based on an extended dataset of 96 lead-drug pairs, of which 62 are lead structures that are not marketed as drugs, and 75 are drugs that are not presumably used as leads. We examined the following properties: MW (molecular weight), CMR (the calculated molecular refractivity), RNG (the number of rings), RTB (the number of rotatable bonds), the number of hydrogen bond donors (HDO) and acceptors (HAC), the calculated logarithm of the n-octanol/water partition (CLogP), the calculated logarithm of the distribution coefficient at pH 7.4 (LogD(74)), the Daylight-fingerprint druglike score (DFPS), and the property and pharmacophore features score (PPFS). The following differences were observed between the medians of drugs and leads: DeltaMW = 69; DeltaCMR = 1.8; DeltaRNG = DeltaHAC =1; DeltaRTB = 2; DeltaCLogP = 0.43; DeltaLogD(74) = 0.97; DeltaHDO = 0; DeltaDFPS = 0.15; DeltaPPFS = 0.12. Lead structures exhibit, on the average, less molecular complexity (less MW, less number of rings and rotatable bonds), are less hydrophobic (lower CLogP and LogD(74)), and less druglike (lower druglike scores). These findings indicate that the process of optimizing a lead into a drug results in more complex structures. This information should be used in the design of novel combinatorial libraries that are aimed at lead discovery.
Therapeutic applications of macrophage colony-stimulating factor-1 (CSF-1) and antagonists of CSF-1 receptor (CSF-1R) signaling (2011)

Macrophage-colony stimulating factor (CSF-1) signaling through its receptor (CSF-1R) promotes the differentiation of myeloid progenitors into heterogeneous populations of monocytes, macrophages, dendritic cells, and bone-resorbing osteoclasts. In the periphery, CSF-1 regulates the migration, proliferation, function, and survival of macrophages, which function at multiple levels within the innate and adaptive immune systems. Macrophage populations elicited by CSF-1 are associated with, and exacerbate, a broad spectrum of pathologies, including cancer, inflammation, and bone disease. Conversely, macrophages can also contribute to immunosuppression, disease resolution, and tissue repair. Recombinant CSF-1, antibodies against the ligand and the receptor, and specific inhibitors of CSF-1R kinase activity have been each been tested in a range of animal models and in some cases, in patients. This review examines the potential clinical uses of modulators of the CSF-1/CSF-1R system. We conclude that CSF-1 promotes a resident-type macrophage phenotype. As a treatment, CSF-1 has therapeutic potential in tissue repair. Conversely, inhibition of CSF-1R is unlikely to be effective in inflammatory disease but may have utility in cancer.
Pulmonary magnetic resonance angiography (1999)

Early attempts to image the pulmonary vasculature with spin-echo magnetic resonance (MR) imaging were hampered by severe image degradation related to respiratory and cardiac pulsation artifact, susceptibility at interfaces between lung parenchyma and vessel wall, and poor contrast between flowing blood and intravascular filling defects of emboli. With the development of gradient-echo MR angiographic techniques some of these limitations were overcome; however, the need for multiple breath-holds and the frequent occurrence of flow-related artifacts that could simulate pulmonary emboli diminished their clinical utility. With the development of contrast-enhanced MR angiography, many of the limitations of earlier techniques were addressed. Images of both lungs with high signal-to-noise ratios and high contrast between flowing blood and pulmonary emboli could be acquired in a single breath-hold, during “first-pass” imaging with extracellular contrast agents in the coronal plane. However, subsegmental vessels could not be assessed with this approach. The technique has been refined further by imaging each lung separately in the sagittal plane; this offers higher resolution and total lung coverage and requires a shorter breath-hold. Finally, several investigators have reported preliminary data on imaging of the pulmonary vasculature with blood pool agents, exploiting respiratory triggering or navigator echoes to eliminate the need for breath-holding for the detection of pulmonary emboli. J. Magn. Reson. Imaging 10:326–338, 1999. © 1999 Wiley-Liss, Inc.
Spectroscopic studies of the electronic structure of iron(III) tris(catecholates) (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpectroscopic studies of the electronic structure of iron(III) tris(catecholates)Timothy B. Karpishin, Matthew S. Gebhard, Edward I. Solomon, and Kenneth N. RaymondCite this: J. Am. Chem. Soc. 1991, 113, 8, 2977–2984Publication Date (Print):April 1, 1991Publication History Published online1 May 2002Published inissue 1 April 1991https://pubs.acs.org/doi/10.1021/ja00008a028https://doi.org/10.1021/ja00008a028research-articleACS PublicationsRequest reuse permissionsArticle Views1101Altmetric-Citations103LEARN 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
Hepatocyte Growth Factor Contributes to Fracture Repair by Upregulating the Expression of BMP Receptors (2005)

This study indicates that HGF is activated and expressed at the fracture site and that HGF induces the upregulation of BMPRs in mesenchymal cells. Furthermore, HGF may facilitate BMP signaling without altering the expression of BMP molecules.
Quantifying the contribution of gluconeogenesis to glucose production in fasted human subjects using stable isotopes (1999)

The contribution of gluconeogenesis to glucose production is estimated from the enrichment of the H bound to C-5 of glucose relative to either that bound to C-2 of glucose or the enrichment in body water on ingesting 2H2O in the fasted state. Contributions of all gluconeogenic substrates are included in the estimate and the limitation of an uncertain precursor enrichment removed. The half-life of 2H2O in body water precludes a repeat study for many weeks. Glycogen cycling could result in underestimation, but there is evidence that glycogen cycling does not occur in liver in the fasted state. Gluconeogenesis has been estimated by mass-isotopomer-distribution analyses, usually by administering 13C-labelled glycerol. Underestimates emphasize the major limitation of the method, i.e. the need to assume a single enrichment of the precursor pool. Estimates of gluconeogenesis from isotopomer distribution in arterial-blood glucose and lactate on infusing [U-13C6] glucose are unreliable, as a proportion of the glucose is formed from glycerol and from amino acids not converted to glucose via pyruvate. Loss of label in the Krebs cycle and relying on enrichment of arterial-blood lactate as a measure of hepatic pyruvate further add to the uncertainty. Estimates of the rate of gluconeogenesis by NMR are obtained by subtraction of the rate of glycogenolysis determined by NMR from the rate of glucose production. Estimates are then the mean rate for the period over which glycogen contents are measured. Technical considerations can limit the accuracy of analyses and result in overestimates.
Inhibition of antigen-induced T cell response and antibody-induced NK cell cytotoxicity by NKG2A: association of NKG2A with SHP-1 and SHP-2 protein-tyrosine phosphatases (1998)

Subsets of T and natural killer (NK) lymphocytes express the CD94-NKG2A heterodimer, a receptor for major histocompatibility complex class I molecules. We show here that engagement of the CD94-NKG2A heterodimer inhibits both antigen-driven tumor necrosis factor (TNF) release and cytotoxicity on melanoma-specific human T cell clones. Similarly, CD16-mediated NK cell cytotoxicity is extinguished by cross-linking of the CD94-NKG2A heterodimer. Combining in vivo and in vitro analysis, we report that both I/VxYxxL immunoreceptor tyrosine-based inhibition motifs (ITIM) present in the NKG2A intracytoplasmic domain associate upon tyrosine phosphorylation with the protein tyrosine phosphatases SHP-1 and SHP-2, but not with the polyinositol phosphatase SHIP Determination of the dissociation constant, using surface plasmon resonance analysis, indicates that NKG2A phospho-ITIM interact directly with the SH2 domains of SHP-1 and SHP-2 with a high affinity. Engagement of the CD94-NKG2A heterodimer therefore appears as a protein-tyrosine phosphatase-based strategy that negatively regulates both antigen-induced T cell response and antibody-induced NK cell cytotoxicity. Our results suggest that this inhibitory pathway sets the threshold of T and NK cell activation.
T Cell Responses to Gram-Negative Intracellular Bacterial Pathogens: A Role for CD8+ T Cells in Immunity to Salmonella Infection and the Involvement of MHC Class Ib Molecules (1999)

Despite being a major group of intracellular pathogens, the role of class I-restricted T cells in the clearance of Gram-negative bacteria is not resolved. Using a murine typhoid model, a role for class I-restricted T cells in the immune response to the Gram-negative pathogen Salmonella typhimurium is revealed. Class I-deficient beta2-microglobulin-/- mice show increased susceptibility to infection with S. typhimurium. Following infection, CD8+ CTLs specific for Salmonella-infected targets can be readily detected. The Salmonella-specific CTLs recognize infected H-2-mismatched targets, suggesting the involvement of shared class Ib molecules. Studies using transfectants expressing defined class Ia and class Ib molecules indicate the involvement of the class Ib molecule, Qa-1. Ab-blocking studies and the measurement of bacteria-specific CTL frequencies identified Qa-1 as a dominant restricting element. The Qa-1-restricted CTL recognition depends on TAP and proteasome functions. Surprisingly, Qa-1-restricted CTLs recognized cells infected with other closely related Gram-negative bacteria. Taken together, these observations indicate that Salmonella-specific CTLs recognize a cross-reactive epitope presented by Qa-1 molecules and, as such, may be novel targets for vaccine development.
The cyclotide family of circular miniproteins: Nature's combinatorial peptide template (2006)

The cyclotides are a recently discovered family of miniproteins that contain a head-to-tail cyclized backbone and a knotted arrangement of disulfide bonds. They are approximately 30 amino acids in size and are present in high abundance in plants from the Violaceae, Rubiaceae, and Cucurbitaceae families, with individual plants containing a suite of up to 100 cyclotides. They have a diverse range of biological activities, including uterotonic, anti-HIV, antitumor, and antimicrobial activities, although their natural function is likely that of defending their host plants from pathogens and pests. This review focuses on the structural aspects of cyclotides, which may be thought of as a natural combinatorial peptide template in which a wide range of amino acids is displayed on a compact molecular core made up of the cyclic cystine knot structural motif. Cyclotides are exceptionally stable and are resistant to denaturation via thermal, chemical, or enzymatic treatments. The structural features that contribute to their remarkable stability are described in this review.