gebhart/patrepeval huggingface dataset:
Anti-C5a receptor antibodies. Characterization of neutralizing antibodies specific for a peptide, C5aR-(9-29), derived from the predicted amino-terminal sequence of the human C5a receptor. (1993)

Results obtained indicate that a site-directed polyclonal antibody specific for a synthetic peptide based on the predicted amino-terminal sequence of human C5aR (anti-C5aR(9-29)) is capable of binding to both normal human and transfected cells bearing C5aR. Flow cytometric analysis of stable murine L cell transfectants (C5aR-neo), human neutrophils, and human monocytes indicated that these cells bound anti-C5aR(9-29) in a specific manner. Moreover, F(ab')2 fragments of anti-C5aR(9-29) specifically neutralized proinflammatory and immunoregulatory activities induced by natural human C5a. This antiserum was found to block, in a dose-dependent manner, 1) zymosan-induced neutrophil chemotaxis, 2) C5a-induced enzyme release from neutrophils, and 3) C5a-induced cytokine production (IL-6 and IL-8) from human monocytes in vitro. These results suggest that this site-directed polyclonal antiserum specifically interacts with the human C5aR molecule. To the best of our knowledge, none of the existing reports in the literature provided evidence for a site-directed antiserum to C5aR that was capable of specifically blocking C5a-mediated inflammatory/immunoregulatory activities in vitro. Studies conducted with anti-C5aR(9-29) indicated that this antiserum effectively blocked C5a-mediated cell activation but by itself did not activate either neutrophils or monocytes. Combined, these data suggest that this antiserum does not interact with the C5a "effector" site but sterically interferes with C5a binding to its receptor by interacting with the extracellular amino-terminal region of the receptor.
Activation of group II metabotropic glutamate receptors inhibits synaptic excitation of the substantia nigra pars reticulata (2000)

Loss of nigrostriatal dopaminergic neurons in Parkinson’s disease (PD) leads to increased activity of glutamatergic neurons in the subthalamic nucleus (STN). Recent studies reveal that the resultant increase in STN-induced excitation of basal ganglia output nuclei is responsible for the disabling motor impairment characteristic of PD. On the basis of this, it is possible that any manipulation that reduces activity at excitatory STN synapses onto basal ganglia output nuclei could be useful in the treatment of PD. We now report that group II metabotropic glutamate receptors (mGluRs) are presynaptically localized on STN terminals and that activation of these receptors inhibits excitatory transmission at STN synapses. In agreement with the hypothesis that this could provide a therapeutic benefit in PD, a selective agonist of group II mGluRs induces a dramatic reversal of catalepsy in a rat model of PD. These results raise
Single nucleotide polymorphism analyses of the human proliferating cell nuclear antigen (pCNA) and flap endonuclease (FEN1) genes (2000)

The products of proliferating cell nuclear antigen (PCNA) and flap endonuclease (FEN1) genes are multifunctional proteins that are involved in DNA replication and damage repair. Yeast models suggest association of mutant forms of PCNA and FEN1 with genomic instability. In our study, we have determined the single nucleotide polymorphisms in human PCNA and FEN1 genes. We sequenced the coding region and adjacent noncoding region of both the PCNA and FEN1 genes in 120 alleles (60 individuals). In the PCNA gene, we detected 9 sequence variants with Hardy-Weinberg allele frequency ranging from 0.008 to 0.088. No polymorphism was detected in the FEN1 gene. The sequence variants in the PCNA gene included 7 intronic single nucleotide polymorphisms (SNP) and 2 synonymous exonic SNPs. All the intronic SNPs were located in introns 1 and 4, which contain several regulatory elements involved in the control of PCNA gene expression. Six of the 7 intronic SNPs showed complete linkage disequilibrium. We confirmed this allelic linkage disequilibrium by allele-specific PCR sequencing. We genotyped 117 additional individuals belonging to 3 population subgroups using the PCR-RFLP method. Finally, to see if the detected polymorphisms are associated with any cancer type, we genotyped cases with melanomas (37 cases), breast cancers (118 cases) and lung cancers (100 cases). We did not find statistical difference in frequency of polymorphism in any cancer type compared with healthy controls, although in breast cancer the frequency was low. Our results suggest that the coding regions of the PCNA and FEN1 genes are highly conserved when compared with other DNA repair genes. The potential of some of the detected intronic polymorphisms to effect regulation of the PCNA gene expression remains to be determined.
The proteosomal degradation of fusion proteins cannot be predicted from the proteosome susceptibility of their individual components (2008)

It is assumed that the proteosome-processing characteristics of fusion constructs can be predicted from the sum of the proteosome sensitivity of their components. In the present study, we observed that a fusion construct consisting of proteosome-degradable proteins does not necessarily result in a proteosome-degradable chimera. Conversely, fusion of proteosome-resistant proteins may result in a proteosome-degradable composite. We previously demonstrated that conserved influenza proteins can be unified into a single fusion antigen that is protective, and that vaccination with combinations of proteosome-resistant and proteosome-degradable antigens resulted in an augmented T-cell response. In the present study we constructed proteosome-degradable mutants of conserved influenza proteins NP, M1, NS1, and M2. These were then fused into multipartite proteins in different positions. The stability and degradation profiles of these fusion constructs were demonstrated to depend on the relative position of the individual proteins within the chimeric molecule. Combining unstable sequences of either NP and M1 or NS1 and M2 resulted in either rapidly proteosome degraded or proteosome-resistant bipartite fusion mutants. However, further unification of the proteosome-degradable forms into a single four-partite fusion molecule resulted in relatively stable chimeric proteins. Conversely, the addition of proteosome-resistant wild-type M2 to proteosome-resistant NP-M1-NS1 fusion protein lead to the decreased stability of the resulting four-partite multigene products, which in one case was clearly proteosome dependent. Additionally, a highly destabilized form of M1 failed to destabilize the wild-type NP. Collectively, we did not observe any additive effect leading to proteosomal degradation/nondegradation of a multigene construct.
Application of the avidin-biotin method of gene enrichment to the isolation of long double-stranded DNA containing specific gene sequences (1977)

A method of enriching for long double-stranded segments of eukaryotic DNA carrying particular genes is described. A purified RNA coded for by the gene is covalently attached to biotin via the protein, cytochrome c. This modified RNA is hybridized to total nuclear, double-stranded DNA under conditions that allow the formation of R-loops. Avidin, which has a high affinity for biotin, is covalently attached to polymer spheres. The complexes of avidin-spheres with DNA:RNA-biotin R-loop hybrids band in CsCl at a much lower bouyant density than does free DNA. This density is a function of the length of DNA coupled per avidin-sphere. This method was used to prepare very long double-strands of DNA highly enriched in the coding sequences for the large rRNAs of D. melanogaster and L. donovani and the histone mRNAs of S. purpuratus.
Antimigraine drug sumatriptan increases blood flow velocity in large cerebral arteries during migraine attacks (1992)

Sumatriptan, a novel selective 5-hydroxytryptamine1d (5-HT1d) receptor agonist, which is highly effective in the acute treatment of migraine attacks, blocks dural neurogenic plasma extravasation and constricts cranial blood vessels in animal experiments. We measured intra- and extracranial blood flow velocities (BFV) with a transcranial Doppler device in 67 patients during a spontaneous migraine attack, before and after treatment with 3 mg or 6 mg subcutaneous sumatriptan or placebo. Sumatriptan, but not placebo, significantly increased BFV (cm/sec) in the internal carotid and middle cerebral arteries on both sides, without detectably changing the BFV in the common and external carotid arteries. The rise in BFV increased with the dose of sumatriptan, parallel to an increase in proportion of patients improved. There were no significant changes in heart rate, blood pressure, or respiratory frequency after treatment with sumatriptan. The increase in BFV probably reflects vasoconstriction of the large basal intracranial arteries, which may be a mechanism for the antimigraine action of sumatriptan.
Genetic Mouse Models of Alzheimer′s Disease (2005)

In the current minireview, we focus on genetic mouse models of Alzheimer's disease (AD). Because various excellent, up-to-date reviews, special issues, and reliable websites are already dedicated to the genetics of Alzheimer's disease in general and of animal models in particular, this review is not meant to be comprehensive. Rather, we aim to steer the Alzheimer's novice through the recent mouse literature on AD. Special attention will be paid to genetic models that have been tested behaviorally.
Estimation of Common Factors Under Cross-Sectional and Temporal Aggregation Constraints: Nowcasting Monthly GDP and Its Main Components (2008)

The paper estimates a large-scale mixed-frequency dynamic factor model for the euro area, using monthly series along with Gross Domestic Product (GDP) and its main components, obtained from the quarterly national accounts. Our model is a traditional dynamic factor model formulated at the monthly frequency in terms of the stationary representation of the variables, which however becomes nonlinear when the observational constraints are taken into account.
Selective inhibition of the contractile apparatus. A new approach to modification of infarct size, infarct composition, and infarct geometry during coronary artery occlusion and reperfusion. (1992)

Selective intracoronary infusion of BDM at doses inhibiting regional wall motion decreased infarct size after reperfusion. The effects of BDM on regional function, the reduction in contraction band necrosis at histology, and the peculiar configuration of these infarcts all suggest that inhibition of contracture can interfere with cell-to-cell progression of myocardial necrosis, supporting a role for contracture in reperfusion-induced cell death.
Real Time Streaming Protocol (RTSP) (1998)

This document is an Internet-Draft. Internet-Drafts are working documents of the Internet Engineering Task Force (IETF), its areas, and its working groups. Note that other groups may also distribute working documents as Internet-Drafts. Internet-Drafts are draft documents valid for a maximum of six months and may be updated, replaced, or obsoleted by other documents at any time. It is inappropriate to use Internet-Drafts as reference material or to cite them other than as “work in progress”. To learn the current status of any Internet-Draft, please check the “1id-abstracts.txt ” listing contained in the Internet-Drafts Shadow Directories on ftp.is.co.za (Africa), nic.nordu.net (Europe), munnari.oz.au (Pacific Rim), ds.internic.net (US East Coast), or ftp.isi.edu (US West Coast). Distribution of this document is unlimited. Copyright Notice Copyright (c) The Internet Society (2002). All Rights Reserved. This memorandum is a revision of RFC 2326, which is currently a Proposed Standard. The Real Time Streaming Protocol, or RTSP, is an application-level protocol for control over the
SIZE LIMITS FOR REGENERATIVE HEAT ENGINES (1998)

This article explores the lower size limit placed on regenerative heat engines by thermodynamics and heat transfer. Information derived in this work has direct relevance to the development of mesoscopic heat engines that are based on standard gas cycles employing regeneration. A model is developed for the Stirling cycle that incorporates a regenerator effectiveness term and an axial conduction term, both of which are dependent on the length scale of the device. The thermal efficiency for the engine is determined in terms of the cycle temperature ratio, the expansion ratio, regenerator effectiveness, and a nondimensional term called the conduction parameter. Results from this study show that a small-scale heat engine fabricated from a low-thermal-conductivity material can be made with a length scale approaching 1 mm. Such a device would undoubtedly be composed of numerous microscale components. Below the 1-mm limit, efficiency suffers to such a degree that solid-state thermoelectric devices would become a better choice for a particular application.
The design and implementation of a framework for configurable software (2002)

Software systems are typically composed of numerous components, each of which is responsible for a different function. Different implementations of a component may be possible, with each implementation tailored for a specific set of applications or environments. Being able to reconfigure software systems to make use of these different implementations with the minimum of effect on existing users and applications is desirable. Configurable software systems are also important for a number of other reasons: additional components or modifications to those currently available, may be required. For example, new versions of software components may be necessary due to the discovery of design flaws in a component; a RPC which provider unreliable message delivery may be suitable for an application in a local area network, but if the application is to be used in a wide area network, a different RPC implementation, which guarantees message delivery, may be necessary. Therefore, software is often required to be configurable, enabling modifications to occur with minimal effect on existing users. To allow this configurability, components should only be available through interfaces that are clearly separated from their implementations, allowing users to be isolated from any implementation changes. Object-oriented programming techniques offer a good basis upon which this separation can be provided. This paper describes a model for constructing configurable software based upon this separation, and illustrates this with a software development system.
Human skeletal muscle xenograft as a new preclinical model for muscle disorders (2014)

Development of novel therapeutics requires good animal models of disease. Disorders for which good animal models do not exist have very few drugs in development or clinical trial. Even where there are accepted, albeit imperfect models, the leap from promising preclinical drug results to positive clinical trials commonly fails, including in disorders of skeletal muscle. The main alternative model for early drug development, tissue culture, lacks both the architecture and, usually, the metabolic fidelity of the normal tissue in vivo. Herein, we demonstrate the feasibility and validity of human to mouse xenografts as a preclinical model of myopathy. Human skeletal muscle biopsies transplanted into the anterior tibial compartment of the hindlimbs of NOD-Rag1(null) IL2rγ(null) immunodeficient host mice regenerate new vascularized and innervated myofibers from human myogenic precursor cells. The grafts exhibit contractile and calcium release behavior, characteristic of functional muscle tissue. The validity of the human graft as a model of facioscapulohumeral muscular dystrophy is demonstrated in disease biomarker studies, showing that gene expression profiles of xenografts mirror those of the fresh donor biopsies. These findings illustrate the value of a new experimental model of muscle disease, the human muscle xenograft in mice, as a feasible and valid preclinical tool to better investigate the pathogenesis of human genetic myopathies and to more accurately predict their response to novel therapeutics.
Carbohydrate binding properties of banana (Musa acuminata) lectin (2001)

This paper extends our knowledge of the rather bizarre carbohydrate binding poperties of the banana lectin (Musa acuminata). Although a glucose/mannose binding protein which recognizes alpha-linked gluco-and manno-pyranosyl groups of polysaccharide chain ends, the banana lectin was shown to bind to internal 3-O-alpha-D-glucopyranosyl units. Now we report that this lectin also binds to the reducing glucosyl groups of beta-1,3-linked glucosyl oligosaccharides (e.g. laminaribiose oligomers). Additionally, banana lectin also recognizes beta1,6-linked glucosyl end groups (gentiobiosyl groups) as occur in many fungal beta1,3/1,6-linked polysaccharides. This behavior clearly distinguishes the banana lectin from other mannose/glucose binding lectins, such as concanavalin A and the pea, lentil and Calystegia sepium lectins.
Conductance of Single Alkanedithiols:  Conduction Mechanism and Effect of Molecule−Electrode Contacts (2006)

The conductance of single alkanedithiols covalently bound to gold electrodes has been studied by statistical analysis of repeatedly created molecular junctions. For each molecule, the conductance histogram reveals two sets of well-defined peaks, corresponding to two different conductance values. We have found that (1) both conductance values decrease exponentially with the molecular length with an identical decay constant, beta approximately equal to 0.84 A(-1), but with a factor of 5 difference in the prefactor of the exponential function. (2) The current-voltage curves of the two sets can be fit with the Simmons tunneling model. (3) Both conductance values are independent of temperature (between -5 and 60 degrees C) and the solvent. (4) Despite the difference in the conductance, the forces required to break the molecular junctions are the same, 1.5 nN. These observations lead us to believe that the conduction mechanism in alkanedithiols is due to electron tunneling or superexchange via the bonds along the molecules, and the two sets of conductance peaks are due to two different microscopic configurations of the molecule-electrode contacts.
HLA-DQ2 and -DQ8 signatures of gluten T cell epitopes in celiac disease (2006)

Celiac disease is associated with HLA-DQ2 and, to a lesser extent, HLA-DQ8. Type 1 diabetes is associated with the same DQ molecules in the opposite order and with possible involvement of trans-encoded DQ heterodimers. T cells that are reactive with gluten peptides deamidated by transglutaminase 2 and invariably restricted by DQ2 or DQ8 can be isolated from celiac lesions. We used intestinal T cells from celiac patients to map DQ2 and DQ8 epitopes within 2 representative gluten proteins, alpha-gliadin AJ133612 and gamma-gliadin M36999. For alpha-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of 2 separate regions. For gamma-gliadin, DQ2- and DQ8-restricted T cells recognized deamidated peptides of the same region. Some gamma-gliadin peptides were recognized by T cells in the context of DQ2 or DQ8 when bound in exactly the same registers, but with different requirements for deamidation; deamidation at peptide position 4 (P4) was important for DQ2-restricted T cells, whereas deamidation at P1 and/or P9 was important for DQ8-restricted T cells. Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes.
Magnetic resonance direct thrombus imaging: a novel technique for imaging venous thromboemboli (2003)

Invasive testing is now seldom required in patients with suspected venous thromboembolism (VTE). However, a corollary of noninvasive imaging is increased complexity as results are often yielded as probabilities rather than definitive answers and additional testing is frequently required following initial imaging. This creates a milieu in which misunderstandings and protocol violations are common, potentially leading to diagnostic errors. A highly accurate noninvasive imaging technique which allows immediate treatment decisions to be made is needed. Magnetic resonance direct thrombus imaging (MRDTI) is a novel technique which detects methaemoglobin in clot, allowing visualisation of thrombus without using intravenous contrast. It has two major advantages over conventional modalities which identify it as having the potential to fill this role. Firstly, direct visualisation of thrombus overcomes many of the pitfalls of conventional techniques, which have either identified thrombus as a filling defect or in terms of surrogates. Secondly, simultaneous imaging of the legs and chest allows a comprehensive assessment of thrombus load, minimising the importance of overlooked subsegmental pulmonary embolism (PE) and potentially facilitating more titrated treatment. Early data suggest MRDTI is highly accurate for the detection of both deep vein thrombosis (DVT) and PE, and ongoing out-come studies are evaluating the safety of withholding treatment in suspected DVT and PE on the basis of negative MRDTI alone. If favorable, a multi-centre outcome study evaluating cost-effectiveness as well as safety would be justified. Subject to further evaluation, this technique has the potential greatly to simplify and standardise the investigation of suspected VTE.
Pathophysiological Mechanisms of Dominant and Recessive KvLQT1 K+ Channel Mutations Found in Inherited Cardiac Arrhythmias (1997)

The inherited long QT syndrome (LQTS), characterized by a prolonged QT interval in the electrocardiogram and cardiac arrhythmia, is caused by mutations in at least four different genes, three of which have been identified and encode cardiac ion channels. The most common form of LQTS is due to mutations in the potassium channel gene KVLQT1, but their effects on associated currents are still unknown. Different mutations in KVLQT1 cause the dominant Romano-Ward (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome, which, in addition to cardiac abnormalities, includes congenital deafness. Co-expression of KvLQT1 with the IsK protein elicits slowly activating potassium currents resembling the cardiac Iks current. We now show that IsK not only changes the kinetics of KvLQT1 currents, but also its ion selectivity. Several mutations found in RW, including a novel mutation (D222N) in the putative channel pore, abolish channel activity and reduce the activity of wild-type KvLQT1 by a dominant-negative mechanism. By contrast, a JLN mutation truncating the carboxyterminus of the KvLQT1 channel protein abolishes channel function without having a dominant-negative effect. This fully explains the different patterns of inheritance. Further, we identified a novel splice variant of the KVLQT1 gene, but could not achieve functional expression of this nor of a previously described heart-specific isoform.