gebhart/patrepeval huggingface dataset:
Human type I interferons: structure and function. (1994)

Human type I interferons (IFNs) comprise a family of 13 IFN-alpha subtypes and single species of IFN-beta and IFN-omega. Their 20% overall sequence homology determines identical secondary and tertiary folding of polypeptides. Three-dimensional models suggest that the globular structure of type I IFNs consists of a bundle of 5 alpha-helices, which might form two polypeptide domains. Disulfide bond Cys 29-Cys 139 stabilizes both domains in a bioactive configuration. The IFN molecule exerts its functional entity only as an organic polypeptide complex and therefore molecular fragments apparently lack biological activity. IFN-beta, IFN-omega and some IFN-alpha subtypes are glycoproteins, but the sugar moiety was found to be neither structurally nor functionally relevant. Type I IFNs share a common cellular receptor, a fact that implies a high structural conservativity of their receptor-binding areas. Two conservative hydrophilic regions associated with the amino acids (aa) 30-41 and 120-145 appear to constitute the basic framework of receptor recognition site in type I IFNs. However, the individual IFN-(sub)types induce different spectra of biological effects which reflect some specificity in modelling of binding sites. Besides a subtle sequential heterogeneity in the segments aa 30-41 and 120-145, also the variable hydrophilic aa regions 23-26, 68-85 and 112-121 are responsible for structural and functional individuality among human type I IFNs. The interaction between IFN and its receptor seems to be a complex event which triggers simultaneously antiviral, antiproliferative and immunomodulating actions, although different parts of IFN molecule are not involved equally in eliciting of respective basal activities.
Activation of LH receptors expressed in GnRH neurons stimulates cyclic AMP production and inhibits pulsatile neuropeptide release. (1996)

The GT1-7 cell line of immortalized GnRH neurons has been shown to express receptors for GnRH, LH, and prolactin, as well as a variety of other hormones and transmitters. Treatment of GT1-7 cells with hCG caused a dose-dependent increase in cAMP production, with a rapid increase during the first 15 min and a subsequent decrease that was prevented by pre-treatment with pertussis toxin. Furthermore, the stimulatory effect of cholera toxin on cAMP production was inhibited by hCG in a dose-dependent manner. These data indicate that the LH receptors expressed in GT1-7 cells are coupled to adenylyl cyclase both stimulatory (Gs) and inhibitory (Gi) proteins. In perifused cell cultures, treatment with forskolin and 8-bromo cAMP increased the amplitude of spontaneous GnRH release. However, treatment with nanomolar concentrations of hCG abolished pulsatile GnRH release from both GT1-7 cells and rat hypothalamic cells. The similarity of hCG action on pulsatile GnRH release to that of extracellular Ca2+ depletion and calcium channel antagonists, and its partial resistance to potassium-induced depolarization, suggest that it results from inhibition of plasma-membrane ion channel activity. It is probable that the inhibitory action of hCG on pulsatile GnRH release is responsible for initiation of the suppression of pituitary LH secretion during pregnancy.
ChemInform Abstract: ALL‐SOLID LITHIUM ELECTRODES WITH MIXED‐CONDUCTOR MATRIX (1981)

Abstract Neuartige feste Verbund‐ ′ elektroden, in denen der Reaktant ( ;z.B. LiyAl oder LiySi) in einer festen gemischtleitenden Matrix wie LiMSn feinverteilt ist, können wiederholten Lade‐Entlade‐Zyklen ausgesetzt werden, ohne daß ein merkbarer Kapazitätsverlust eintritt.
DISC1 Regulates Neurotrophin-Induced Axon Elongation via Interaction with Grb2 (2007)

Disrupted-in-Schizophrenia-1 (DISC1) is a candidate gene for susceptibility of schizophrenia. In the accompanying paper (Taya et al., 2006), we report that DISC1 acts as a linker between Kinesin-1 and DISC1-interacting molecules, such as NudE-like, lissencephaly-1, and 14-3-3epsilon. Here we identified growth factor receptor bound protein 2 (Grb2) as a novel DISC1-interacting molecule. Grb2 acts as an adaptor molecule that links receptor tyrosine kinases and the Ras-extracellular signal-regulated kinase (ERK) pathway. DISC1 formed a ternary complex with Grb2 and kinesin heavy chain KIF5A of Kinesin-1. In cultured rat hippocampal neurons, both DISC1 and Grb2 partially colocalized at the distal part of axons. Knockdown of DISC1 or kinesin light chains of Kinesin-1 by RNA interference inhibited the accumulation of Grb2 from the distal part of axons. Knockdown of DISC1 also inhibited the neurotrophin-3 (NT-3)-induced phosphorylation of ERK-1/2 at the distal part of axons and inhibited NT-3-induced axon elongation. These results suggest that DISC1 is required for NT-3-induced axon elongation and ERK activation at the distal part of axons by recruiting Grb2 to axonal tips.
SideSight (2008)

Interacting with mobile devices using touch can lead to fingers occluding valuable screen real estate. For the smallest devices, the idea of using a touch-enabled display is almost wholly impractical. In this paper we investigate sensing user touch around small screens like these. We describe a prototype device with infra-red (IR) proximity sensors embedded along each side and capable of detecting the presence and position of fingers in the adjacent regions. When this device is rested on a flat surface, such as a table or desk, the user can carry out single and multi-touch gestures using the space around the device. This gives a larger input space than would otherwise be possible which may be used in conjunction with or instead of on-display touch input. Following a detailed description of our prototype, we discuss some of the interactions it affords.
Blood Transfusion and Risk of Non-Hodgkin's Lymphoma in Connecticut Women (2004)

The incidence and mortality rates of non-Hodgkin's lymphoma have been increasing worldwide. Allogeneic blood transfusion has been suggested as a risk factor for non-Hodgkin's lymphoma, but the results from epidemiologic studies have been inconsistent. Data from a population-based case-control study of Connecticut women were analyzed to evaluate this relation. A total of 601 histologically confirmed, non-Hodgkin's lymphoma incident cases identified between 1996 and 2000 and 717 randomly selected controls were included in this study. Allogeneic blood transfusion was not associated with the increased risk of non-Hodgkin's lymphoma overall (odds ratio = 1.0, 95% confidence interval: 0.7, 1.3) or by subtype of the disease. The risk also did not vary by number of allogeneic blood transfusions, age at first transfusion, or time since first transfusion. When the reason for blood transfusion was considered, an increased risk of non-Hodgkin's lymphoma was found only for allogeneic blood transfusion for reason of anemia. In summary, the authors' findings do not support the hypothesis that allogeneic blood transfusion increases the risk of non-Hodgkin's lymphoma.
Protein Replacement Therapies for Rare Diseases: A Breeze for Regulatory Approval? (2013)

Protein replacement therapies for rare monogenic diseases have a higher probability of regulatory approval compared with biologics, small molecules, and grant-funded orphan drugs.
RSA/SHA-1 SIGs and RSA KEYs in the Domain Name System (DNS) (2001)

This document describes how to produce RSA/SHA1 SIG resource records (RRs) in Section 3 and, so as to completely replace RFC 2537, describes how to produce RSA KEY RRs in Section 2.
Direct Observation of a 14-Electron Ruthenacyclobutane Relevant to Olefin Metathesis (2005)

The 14-electron ruthenium phosphonium alkylidene complex [(IH2Mes)Cl2Ru=CH(PCy3)][B(C6F5)4], 1b, a highly active olefin metathesis catalyst, reacts with stoichiometric quantities of ethylene at -50 degrees C in CD2Cl2 to generate the ruthenacyclobutane complex [(IH2Mes)Cl2RuCH2CH2CH2], 2, and [CH2=CH(PCy3)][B(C6F5)4] in quantitative yield by NMR spectroscopy. 1H and 13C NMR spectroscopies on 2 and 2-13C3 are consistent with a symmetrical C2v structure, providing the first experimental information concerning this crucial intermediate in ruthenium-mediated olefin metathesis. At -50 degrees C, exchange with free ethylene takes place on the chemical time scale. Complex 2 decomposes in solution upon warming to room temperature, generating propene and unknown ruthenium product(s).
pH‐Dependent Binding of Synthetic β‐Amyloid Peptides to Glycosaminoglycans (1993)

The senile plaques found within the cerebral cortex and hippocampus of the Alzheimer disease brain contain beta-amyloid peptide (A beta) fibrils that are associated with a variety of macromolecular species, including dermatan sulfate proteoglycan and heparan sulfate proteoglycan. The latter has been shown recently to bind tightly to both amyloid precursor protein and A beta, and this binding has been attributed largely to the interaction of the core protein of heparan sulfate proteoglycan with A beta and its precursor. Here we have examined the ability of synthetic A beta s to bind to and interact with the glycosaminoglycan moieties of proteoglycans. A beta(1-28) associates with heparin, heparan sulfate, dermatan sulfate, and chondroitin sulfate. The interaction of these sulfated polysaccharides with the amyloid peptide results in the formation of large aggregates that are readily sedimented by centrifugation. The ability of both A beta(1-28) and A beta(1-40) to bind glycosaminoglycans is pH-dependent, with increasing interaction as the pH values fall below neutrality and very little binding at pH 8.0. The pH profile of heparin-induced aggregation of A beta(1-28) has a midpoint pH of approximately 6.5, suggesting that one or more histidine residues must be protonated for binding to occur. Analysis of the A beta sequence reveals a consensus heparin-binding domain at residues 12-17, and this motif contains histidines at positions 13 and 14 that may be involved in the interaction with glycosaminoglycans.(ABSTRACT TRUNCATED AT 250 WORDS)
Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3 (2006)

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are both relentlessly progressive and ultimately fatal neurological disorders. ALS is familial in approximately 10% of cases and FTD in approximately 30%. Inheritance is usually autosomal dominant with variable penetrance. Phenotypic overlap between ALS and FTD can occur within the same kindred. Mutations in copper/zinc superoxide dismutase 1 (SOD1) are found in approximately 20% of familial and approximately 3% of sporadic ALS cases but are not associated with dementia. Mutations in microtubule associated protein tau (MAPT) are detected in approximately 30% of familial FTD kindreds. Dominant ALS with FTD has previously been linked to 9q21 and pure ALS to loci on 16q21, 18q21, 20p13. Here we report the results of a genome-wide linkage study in a large ALS and FTD kindred using Affymetrix 10K GeneChip microarrays. Linkage analysis of single nucleotide polymorphism (SNP) data identified consistently positive log of the odds (LOD) scores across chromosome 9p (maximal LOD score of 2.4). Fine mapping the region with microsatellite markers generated a maximal multipoint LOD score of 3.02 (theta = 0) at D9S1878. Recombination narrowed the conserved haplotype to 12 cM (11 Mb) at 9p13.2-21.3 (flanking markers D9S2154 and D9S1874). Bioinformatic analysis of the region has identified 103 known genes.
Rescue of DMARD failures by means of monoclonal antibodies or biological agents. (1997)

Over the past decade different monoclonal antibodies or other biological agents have been developed to complete the available therapeutic repertoire for treating RA patients. Thus, monoclonal antibodies to block the TNF-alpha or TNF-alpha receptor fusion proteins, respectively, have been successfully applied in the treatment of RA patients refractory to other treatment principles. In addition, using the IL-1 receptor antagonist, similar promising data have been obtained in placebo-controlled, double-blind trials. Initial attempts are presently being conducted to test combination therapies, using monoclonal antibodies directed against the proinflammatory cytokines and cell surface molecules, and long-acting rheumatic drugs such as methotrexate. Hopefully within the next few years newly developed biological agents will be available for use in daily clinical practice.
Porcine Extrahepatic Vascular Endothelial Asialoglycoprotein Receptor 1 Mediates Xenogeneic Platelet Phagocytosis In Vitro and in Human-to-Pig Ex Vivo Xenoperfusion (2015)

The ASGR1 expressed on aortic and limb arterial pig vascular endothelium plays a role in binding and phagocytosis of human platelets. Therefore, ASGR1 may represent a novel therapeutic target to overcome thrombocytopenia associated with vascularized pig-to-primate xenotransplantation.
Programmable DNA Self-Assemblies for Nanoscale Organization of Ligands and Proteins (2005)

We demonstrate the precise control of periodic spacing between individual protein molecules by programming the self-assembly of DNA tile templates. In particular, we report the application of two self-assembled periodic DNA structures, two-dimensional nanogrids, and one-dimensional nanotrack, as template for programmable self-assembly of streptavidin protein arrays with controlled density.
Mechanism of cGMP-mediated protection in a cellular model of myocardial reperfusion injury (2005)

We conclude that cGMP-dependent signals activate SERCA via a protein kinase G-dependent phosphorylation of phospholamban. The increase in SERCA activity seems to reduce peak [Ca(2+)](i) and [Ca(2+)](i) oscillation during reoxygenation and to attenuate the excessive activation of the contractile machinery that otherwise leads to the development of hypercontracture.
COUPLING OF IMMUNOASSAYS WITH ENZYMATIC RECYCLING ELECTRODES (2001)

Enzymatic substrate regeneration is a tool to enhance the sensitivity of enzyme electrodes both for substrate analysis and immunoassays. The combination of immunoreactions and electrode based substrate recycling connects specific recognition of an analyte with highly sensitive detection. Most important for this field of application is the sensitivity, which permits to detect a label at very low concentration. Enzymatic substrate regenerating systems are reviewed which are based on sensors using acceptor dependent dehydrogenases in combination with phenol oxidases and the lactate oxidase/lactate dehydrogenase couple and applied as sensitive label detectors in electrochemical immunoassays. Label compounds are either redox-active dyes or enzymes. The label enzymes measured so far are alkaline phosphatase and ß-galactosidase.
A House of Cards Structure in Polypropylene/Clay Nanocomposites under Elongational Flow (2001)

This Letter describes the first real space observation for the formation of a house of cards structure in polypropylene/clay nanocomposite melt under elongational flow by TEM analysis. Both strong strain-induced hardening and rheopexy features are originated from the perpendicular alignment of the silicate layers to the stretching direction.
Spliced adenovirus-associated virus RNA. (1979)

We describe the structure of cytoplasmic RNA species transcribed from the DNA of adenovirus-associated virus, a defective parvovirus. The RNA was hybridized with minus strand template DNA and visualized in the electron microscope. Alternatively, the DNA.RNA duplex molecules were digested with nuclease S1 or Escherichia coli exonuclease VII and analyzed by agarose gel electrophoresis. A set of RNA species was observed with 5' terminal at map positions 5, 13, 19, or 39 and a 3' terminus and poly(A) tail at position 96 (one map unit is equivalent to 1% of genome length). Most of these RNAs are spliced and lack sequences approximately between positions 40 and 49. Some RNA preparations also contained unspliced molecules with 5' and 3' terminal at positions similar to those in the spliced RNA.
Efficient Transformation of Methyl Propargyl Ethers into α,β-Unsaturated Ketones (1991)

Abstract Methyl propargyl ethers, obtained from carbonyl compounds by successive treatment with an acetylide and MeI, were easily converted to the corresponding α,β-unsaturated ketone by regioselective hydration of acetylenic moiety followed by elimination of methanol under the catalytic action of Au(III).
Characterization of diverse natural variants of CYP102A1 found within a species of Bacillus megaterium (2011)

An extreme diversity of substrates and catalytic reactions of cytochrome P450 (P450) enzymes is considered to be the consequence of evolutionary adaptation driven by different metabolic or environmental demands. Here we report the presence of numerous natural variants of P450 BM3 (CYP102A1) within a species of Bacillus megaterium. Extensive amino acid substitutions (up to 5% of the total 1049 amino acid residues) were identified from the variants. Phylogenetic analyses suggest that this P450 gene evolve more rapidly than the rRNA gene locus. It was found that key catalytic residues in the substrate channel and active site are retained. Although there were no apparent variations in hydroxylation activity towards myristic acid (C14) and palmitic acid (C16), the hydroxylation rates of lauric acid (C12) by the variants varied in the range of >25-fold. Interestingly, catalytic activities of the variants are promiscuous towards non-natural substrates including human P450 substrates. It can be suggested that CYP102A1 variants can acquire new catalytic activities through site-specific mutations distal to the active site.
Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non‐anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double‐blind placebo‐controlled clinical trial (the PROTECT trial) (2015)

A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed.
Topical application of CD362+ human mesenchymal stem cells (cyndacel-M) seeded in Excellagen scaffold augments wound healing and increases angiogenesis in a diabetic rabbit ulcer model (2015)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
Creatinine Clearance: Bedside Estimate (1973)

Letters1 October 1973Creatinine Clearance: Bedside EstimateROGER W. JELLIFFE, M.D.ROGER W. JELLIFFE, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-79-4-604 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Previously described computer programs have shown their ability to estimate endogenous creatinine clearance (Ccr) with reasonable accuracy when urine specimens cannot be obtained to calculate endogenous creatinine clearance in the standard manner (1). Such estimates have been very useful for planning drug dosage regimens for patients (2, 3) : they have been based on stable or changing serum creatinine levels, age, sex, height, and weight.When the serum creatinine level is stable, however, and the patient is an adult from 20 to 80 years old, a bedside estimate that closely approaches those of the computer programs may...References1. JELLIFFEJELLIFFE RS: A computer program for estimation of creatinine clearance from unstable serum creatinine levels, age, sex, and weight. Mathematical Biosciences 14:17-24, 1972 CrossrefGoogle Scholar2. JELLIFFE R: New developments in drug dosage regimens. Journal Mondiat de Pharmacie 15:53-78, 1972 Google Scholar3. JELLIFFEBUELLKALABA RJR: Reduction of digitalis toxicity by computer-assisted glycoside dosage regimens. Ann Intern Med 77:891-906, 1972 LinkGoogle Scholar4. SIERSBAEK-NIELSENMOLHOLM HANSENKAMPMAN KJJ: Rapid evaluation of creatinine clearance. Lancet 1:1133-1134, 1971 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROGER W. JELLIFFE, M.D.Affiliations: University of Southern California School of Medicine Los Angeles, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEstimating Equations for Glomerular Filtration Rate in the Era of Creatinine Standardization A Systematic ReviewAmy Earley, BS, Dana Miskulin, MD, MS, Edmund J. Lamb, PhD, Andrew S. Levey, MD, and Katrin Uhlig, MD, MSA More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction EquationAndrew S. Levey, MD, Juan P. Bosch, MD, Julia Breyer Lewis, MD, Tom Greene, PhD, Nancy Rogers, MS, and David Roth, MD, for the Modification of Diet in Renal Disease Study Group*Predicted Creatinine ClearanceTOBIAS L. YEH, PHARM.D., RAYMOND D. SILKAITIS, PH. D.Creatinine Clearance and AgeREED E. PYERITZ, M.D., PH.D.Estimation of Creatinine ClearanceMICHAEL D. ROBSON, M.R.C.P. 1 October 1973Volume 79, Issue 4Page: 604-605KeywordsCreatinineSoftware tools ePublished: 13 March 2020 Issue Published: 1 October 1973 PDF downloadLoading ...
ChemInform Abstract: Evaluation of Substituted β‐Carbolines as Noncompetitive Indolamine 2,3‐Dioxygenase Inhibitors. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The Role of Neurotrophins in Axonal Growth, Guidance, and Regeneration (2007)

Neurotrophins are proteins that regulate neuronal survival, axonal growth, synaptic plasticity and neurotransmission. They are members of the neurotrophic factors family and include factors such as the nerve growth factor (NGF), the brain derived neurotrophic factor (BDNF), the neurotrophin-3 (NT-3), and the neurotrophin-4/5 (NT-4/5). These molecules bind to two types of receptors: i) tyrosine kinase receptors (TrkA, TrkB, TrkC) and ii) a common neurotrophin receptor (p75NTR). The two receptor types can either suppress or enhance each other's actions. Neurotrophins have a multifunctional role both in the central and peripheral nervous system. They have been suggested as axonal guidance molecules during the growth and regeneration of nerves. It has also been proven that they stimulate axonal growth by mediating the polymerization and accumulation of F-actin in growth cones and axon shafts. Neurotrophins, as other neurotrophic factors, have been shown that they reduce neuronal injury by exposure to excitotoxins, glucose deprivation, or ischemia. Furthermore, the nerve regeneration promoting effect of these growth factors is well documented for many different models of central or peripheral nervous system injury. Several studies have shown that exogenous administration of these factors has protective properties for injured neurons and stimulates axonal regeneration. Based on these properties, these molecules may be used as therapeutic agents for treating degenerative diseases and traumatic injuries of both the central and peripheral nervous system.