gebhart/patrepeval huggingface dataset:
Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a (2002)

Voltage-gated sodium channels drive the initial depolarization phase of the cardiac action potential and therefore critically determine conduction of excitation through the heart. In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation. The pathophysiological basis of these clinical conditions is unresolved. Here we show that disruption of the mouse cardiac sodium channel gene, Scn5a, causes intrauterine lethality in homozygotes with severe defects in ventricular morphogenesis whereas heterozygotes show normal survival. Whole-cell patch clamp analyses of isolated ventricular myocytes from adult Scn5a(+/-) mice demonstrate a approximately 50% reduction in sodium conductance. Scn5a(+/-) hearts have several defects including impaired atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation. These findings reconcile reduced activity of the cardiac sodium channel leading to slowed conduction with several apparently diverse clinical phenotypes, providing a model for the detailed analysis of the pathophysiology of arrhythmias.
Acquired haemophilia A: A 2013 update (2013)

Acquired haemophilia A (AHA) is a rare but often severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). AHA occurs more frequently in the elderly and in association with several conditions, such as the post-partum period, malignancies, autoimmune diseases or drug exposure; however, approximately 50% of reported cases are apparently idiopathic. Beside the elimination of the underlying disorder, the therapeutic approach to AHA should be directed toward the control of acute bleed and the eradication of FVIII autoantibody production. In this narrative review, we summarise the current knowledge on the epidemiology, diagnosis and clinical features of AHA, focusing in particular on advances in the management of this challenging bleeding disorder.
Generation of suppressor cells by aggregated human globulin. (1981)

We have studied the capacity of aggregated human globulin, a model for immune complexes, to induce suppressor cells which modulate a predominantly T cell response, i.e. the proliferative response of autologous mononuclear cells to concanavalin A. We utilized a soluble aggregated human globulin preparation depleted of both high molecular weight (greater than 4 x 10(6) daltons) insoluble aggregates and monomeric IgG. The mean per cent suppression induced by mononuclear cells preincubated with aggregated human globulin for 96 hr was 39 +/- 8%; monomeric IgG did not induce significant suppression (4 +/- 6%). We found a close correlation between the magnitude of suppression induced by preincubation for 96 hr with aggregated human globulin and that induced by preincubation with concanavalin A. Kinetic analysis indicated that suppressor cell induction by aggregated human globulin required 48 hr of preincubation; suppressor cell induction by concanavalin A required 24 hr. Aggregated human globulin-induced suppression was not associated with DNA synthesis as measured by 3H-thymidine uptake. The findings suggest that immune complexes can modulate immunoregulation.
Controlling grafting density and side chain length in poly(n‐butyl acrylate) by ATRP copolymerization of macromonomers (2006)

Abstract Atom transfer radical polymerization (ATRP) was used for the preparation and subsequent copolymerization of two acryloyl‐terminated poly( n ‐butyl acrylate) macromonomers with different degrees of polymerization (DP n BA = 25 and 42). Homopolymerization of the higher molecular weight macromonomer ( MM1 ; P n BA 42 ‐A, M n = 5600, DP MM = 42, M w / M n = 1.18) resulted in preparation of a densely grafted polymer with a narrow molecular weight distribution ( M w / M n = 1.14), but with the limited degree of polymerization DP = 12. The ultimate degree of homopolymerization for the lower molecular weight macromonomer ( MM2 ; P n BA 25 ‐A, M n = 3400, DP MM = 25, M w / M n = 1.20) was higher, and DP increased from 12 to 22. The limited DP could be because of progressively increasing steric congestion for macromonomers in approaching the growing chain ends of densely grafted polymers. When MMs were copolymerized with n BA, the reactivity of MM was nearly the same as that of n BA monomer irrespective of the differences in the degree of polymerization of the MMs and the initial molar ratio of n BA to MM. Well‐defined graft polymers with different lengths of backbone and side chains, and different graft density were successfully prepared by “grafting through” ATRP. Tadpole‐shaped and dumbbell‐shaped graft polymers were also synthesized by ATRP. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5454–5467, 2006
Digital halftoning using a blue noise mask (1991)

A new digital halftoning algorithm in which the halftoning algorithm is achieved by a pixelwise comparison of the gray scale image against a non-image array, the blue noise mask, is proposed. The blue noise mask is constructed such that when thresholded at any level, the resulting binary pattern has the correct first order statistics, and also its power spectrum has blue noise (high frequency) characteristics which are visually pleasing. The construction of the blue noise mask is described and experimental results are shown. Results from a psychovisual study are provided where subjects rated halftoned images that have the same first order but different second order statistics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Endothelial cell protein C receptor cellular localization and trafficking: potential functional implications (2009)

Although the binding of endothelial cell protein C receptor (EPCR) to its ligands is well characterized at the biochemical level, it remains unclear how EPCR interaction with its ligands at the cell surface impacts its cellular trafficking. We characterized the cellular localization and trafficking of EPCR in endothelial cells and a heterologous expression system. Immunofluorescence confocal microscopy studies revealed that a majority of EPCR is localized on the cell surface in membrane microdomains that are positive for caveolin-1. A small fraction of EPCR is also localized intracellularly in the recycling compartment. Factor VIIa (FVIIa) or activated protein C binding to EPCR promoted the internalization of EPCR. EPCR and EPCR-bound ligands were endocytosed rapidly via a dynamin- and caveolar-dependent pathway. The endocytosed receptor-ligand complexes were accumulated in a recycling compartment before being targeted back to the cell surface. EPCR-mediated FVIIa endocytosis/recycling also resulted in transport of FVIIa from the apical to the basal side. In vivo studies in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early phase of FVIIa clearance. Overall, our results show that FVIIa or activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may facilitate the transcytosis of FVIIa and its clearance from the circulation.
PLX4032, a potent inhibitor of the B‐Raf V600E oncogene, selectively inhibits V600E‐positive melanomas (2010)

Targeted intervention of the B-Raf V600E gene product that is prominent in melanoma has been met with modest success. Here, we characterize the pharmacological properties of PLX4032, a next-generation inhibitor with exquisite specificity against the V600E oncogene and striking anti-melanoma activity. PLX4032 induces potent cell cycle arrest, inhibits proliferation, and initiates apoptosis exclusively in V600E-positive cells in a variety of in vitro experimental systems; follow-up xenograft studies demonstrate extreme selectivity and efficacy against melanoma tumors bearing the V600E oncoproduct. The collective data support further exploration of PLX4032 as a candidate drug for patients with metastatic melanoma; accordingly, validation of PLX4032 as a therapeutic tool for patients with melanoma is now underway in advanced human (Phase III) clinical trials.
The rapport multimedia conferencing system (1988)

This paper describes the design and initial implementation of the Rapport multimedia conferencing system, which supports interactive, real-time, distributed conferences among two or more users. Using computers connected by data and voice networks, this system creates an environment in which many sorts of meetings can take place, including telephone conversations, discussions among colleagues, and lectures. Rapport provides new opportunities for meetings, allowing a user to interact with distant colleagues and to participate in several conferences concurrently at his or her workstation. The system allows many existing computer programs to be used, unmodified, within its conferencing environment. Thus computer-generated data and displays are available to the conferees for manipulation and editing, enhancing the exchange of information during meetings. Although Rapport does not encourage a particular methodology of meeting conduct, such specialized support can be built using Rapport. The paper outlines Rapport's conference abstraction and the model on which it is based — the “virtual meeting room.” It then presents an overview of Rapport's architecture, discusses the system's environmental requirements, and concludes by mentioning some of our plans for future work with Rapport.
Characterization, subsite mapping and partial amino acid sequence of glucoamylase from the filamentous fungus Trichoderma reesei (1995)

The pH optimum, temperature-dependence, thermal stability, substrate specificity and subsite affinities of the 66 kDa, pI 4.0 glucoamylase of the filamentous fungus Trichoderma reesei were determined. It had a pH optimum of 5.5 and a temperature optimum (5 min reaction time) of 70 degrees C with soluble starch as substrate. Thermal-inactivation studies revealed that the glucoamylase is relatively thermostable up to 60 degrees C. Metal ions and EDTA tested at 5 mM concentrations had no significant effect, and beta-cyclodextrin only slightly inhibitory effects, on the digestion of soluble starch. Estimated Km and kcat. values for soluble starch where 0.11 mg.ml-1 and 28.5 s-1 respectively. Hydrolysis of pullulan (Km 14 mg.ml-1 and kcat. = 6.6 s-1) indicated substantial activity towards 1,6-O-glucosidic bonds. From ratios of kinetic parameters of malto- and isomalto-oligosaccharides, it was apparent that the glucoamylase showed approx. 3-fold higher selectivity towards isomalto-oligosaccharides than most other reported fungal glucoamylases. Substrate binding affinities were calculated from kinetic data for the linear series of malto- and isomalto-oligosaccharides. The results were in good agreement with other reported glucoamylases. The main difference was that subsite 1 showed a slightly negative free energy of binding with malto-oligosaccharides, whereas most other glucoamylases show a positive free energy at this subsite. A set of peptides obtained from purified glucoamylase by tryptic digestion where sequenced. They covered approx. 17% of the total amino acid sequence as estimated from molecular mass on SDS/PAGE. Some of the sequences were tentatively aligned to known glucoamylase sequences. They showed about 60% identity with the extensively studied Aspergillus glucoamylase.
Closed Vitreous Surgery (1980)

Two hundred consecutive closed vitrectomies through the pars plana were observed for at least five years after operation to determine the results and analyze the complications. Vitrectomy was performed to remove vitreous opacities in 56.5% of the eyes (group 1), as a preliminary procedure in the course of retinal reattachment in 42% (group 2), and to reconstruct the anterior segment in 1.5% (group 3). Of the group 1 eyes for which adequate follow-up data were available, visual acuity improved notably in 64.2% showed no change in 11.3%, and deteriorated in 24.5%. The respective percentages for the other groups were as follows: 23.3%, 19.2%, and 57.5% for group 2; and 0%, +66.7%, and +33.3% for group 3. The most common complication during operation was bleeding in the vitreous, especially in diabetic patients; retinal break, lens injury, and vitreous-base avulsion followed in frequency. Postoperative bleeding occurred in 23% of eyes but usually resolved spontaneously and required no further surgery. There was postoperative glaucoma in 20% of the eyes. Corneal decompensation (15% of all cases) and rubeosis iridis (also 15%) had a propensity to occur in diabetic patients. Multiple procedures seemed to predispose eyes undergoing vitrectomy to rubeosis. Fibrous ingrowth into the vitreous through the sclerotomy was seen in five eyes and was associated with retinal detachment in one.
Levels and pattern of alkyl nitrates, multifunctional alkyl nitrates, and halocarbons in the air over the Atlantic Ocean (2000)

The Albatross Campaign was a research cruise of the German research vessel RV Polarstern (cruise ANT XFV/1) in October and November 1996 across the Atlantic Ocean. The cruise started in Bremerhaven, Germany, reached the polar region at 67°N, followed the 30°W meridian longitude, crossed the equatorial region, and ended at 50°S at Punta Quilla, Argentina. A second cruise leg closer to the African continent started from Capetown, South Africa, passed the Canary Island, and ended through the English Channel at Bremerhaven, Germany, in May/June 1998. Measurements of atmospheric levels of C 1 –C 13 alkyl mononitrates, 24 alkyl dinitrates (C 3 –C 6 ), 19 hydroxy alkyl nitrates (C 2 –C 6 ), and benzyl nitrate, as well as the halocarbons tetrachloroethene, hexachloroethane, and bromoform are presented in this work. The halocarbons are used to assess the origin of the air parcels analyzed. Levels and patterns of multifunctional alkyl nitrates in the marine air are described here for the first time. The air masses include polluted air from the northern Europe, as well as highly degraded air masses of the South Atlantic trade wind region that represent global baseline levels. Two independent analytical methods were used in combination to cover the whole range of organic nitrates. First, the low‐volume adsorptive enrichment of organic traces on Tenax, followed by thermodesorption cold trap HRGC‐ECD and thermodesorption cold trap HRGC‐(EI)MSD was used. Second, high‐volume adsorptive enrichment of organic traces on silica gel was applied followed by solvent desorption, NP‐HPLC group separation, and HRGC‐(EI)‐MSD. Short‐chain alkyl nitrates (C 4 –C 6 ) showed mixing ratios in the range of 0.2–2.5 parts per trillion by volume (pptv), with a local minimum for the tropical regions and significantly lower ratios for the Southern Hemisphere. The mixing ratio of the sum of 36 long‐chain alkyl mononitrates (C 7 –C 13 ) ranged from 0.02–0.43 pptv, the mixing ratio of the sum of 23 alkyl dinitrates (C 3 –C 6 ) ranged from 0.005–1.08 pptv, and the mixing ratio of the sum of 7 hydroxy alkyl nitrates (C 2 –C 4 ) ranged from 0.005–1.07 pptv, respectively. The average alkyl nitrate concentration in ambient air of central Europe (Ulm, Germany) turned out to be a factor of 10–100 higher than in the marine samples. The low concentrations in marine air reflect chemical and physical loss processes during long‐range transport of the air starting from the continents. Our results are compared with earlier field studies to complete the data set of global occurrence of alkyl nitrates in the troposphere.
Pdx1 restores β cell function in Irs2 knockout mice (2002)

The homeodomain transcription factor Pdx1 is required for pancreas development, including the differentiation and function of β cells. Mutations in Pdx1 or upstream hepatocyte nuclear factors cause autosomal forms of early-onset diabetes (maturity-onset diabetes of the young [MODY]). In mice, the Irs2 branch of the insulin/Igf signaling system mediates peripheral insulin action and pancreatic β cell growth and function. To investigate whether β cell failure in Irs2–/– mice might be related to dysfunction of MODY-related transcription factors, we measured the expression of Pdx1 in islets from young Irs2–/– mice. Before the onset of diabetes, Pdx1 was reduced in islets from Irs2–/– mice, whereas it was expressed normally in islets from wild-type or Irs1–/– mice, which do not develop diabetes. Whereas male Irs2–/–Pdx1+/+ mice developed diabetes between 8 and 10 weeks of age, haploinsufficiency for Pdx1 caused diabetes in newborn Irs2–/– mice. By contrast, transgenic expression of Pdx1 restored β cell mass and function in Irs2–/– mice and promoted glucose tolerance throughout life, as these mice survived for at least 20 months without diabetes. Our results suggest that dysregulation of Pdx1 might represent a common link between ordinary type 2 diabetes and MODY.
iSMS: an integration platform for short message service and IP networks (2001)

This article describes iSMS, a platform that integrates IP networks with the short message service in mobile telephone systems. iSMS provides a generic gateway for creating and hosting wireless data services for mobile stations. Our approach does not require any modification to the mobile telephone system architecture. The iSMS system can be quickly developed and operated by a third party or end user without involvement of mobile equipment manufacturers and telecom operators. Based on the iSMS platform, we illustrate services such as e-mail delivery/forwarding, Web access (e.g., stock and train schedule query) and handset music services. The iSMS platform and the services have been implemented for GSM networks. With iSMS, users are able to use standard GSM handsets to access wireless Internet services, while other approaches like the Wireless Application Protocol and SIM Toolkit services require function-enabled MSs.
‘Pious Flames’: European encounters withSatibefore 18051 (2004)

On 4 December 1829 the governor‐general of India Lord William Bentinck promulgated a regulation prohibiting the burning or burying alive of Hindu widows. This interference with Hindu custom was jus...
Exploiting structure similarity in refinement: automated NCS and target-structure restraints inBUSTER (2012)

Maximum-likelihood X-ray macromolecular structure refinement in BUSTER has been extended with restraints facilitating the exploitation of structural similarity. The similarity can be between two or more chains within the structure being refined, thus favouring NCS, or to a distinct 'target' structure that remains fixed during refinement. The local structural similarity restraints (LSSR) approach considers all distances less than 5.5 Å between pairs of atoms in the chain to be restrained. For each, the difference from the distance between the corresponding atoms in the related chain is found. LSSR applies a restraint penalty on each difference. A functional form that reaches a plateau for large differences is used to avoid the restraints distorting parts of the structure that are not similar. Because LSSR are local, there is no need to separate out domains. Some restraint pruning is still necessary, but this has been automated. LSSR have been available to academic users of BUSTER since 2009 with the easy-to-use -autoncs and -target target.pdb options. The use of LSSR is illustrated in the re-refinement of PDB entries 5rnt, where -target enables the correct ligand-binding structure to be found, and 1osg, where -autoncs contributes to the location of an additional copy of the cyclic peptide ligand.
Molecular cloning of a novel gene similar to myeloid antigen CD33 and its specific expression in placenta (1997)

We have isolated a novel gene that encodes a protein sharing significant similarity with myeloid antigen CD33. The complete cDNA contains an open reading frame of 1,326 nucleotides encoding 442 amino acids. The deduced amino acid sequence indicates that this molecule belongs to the immunoglobulin (Ig) superfamily and is likely to be a new member of the sialoadhesin sub-family. It is composed of three Ig-like domains; its high degree of similarity to CD33 (70% identity) in the first and second of these domains implies that the placenta-specific gene product is likely to be associated with cell-cell interaction. Northern-blot analysis revealed transcripts of four distinct sizes, 7.5 kb, 5.0 kb, 4.1 kb, and 2.0 kb, specifically in the placenta. Consequently, we termed this gene CD33L (CD33 antigen-like). An alternatively-spliced transcript encoding a 342-amino-acid peptide which lacked the transmembrane region and the cytoplasmic tail was also isolated. We mapped CD33L by fluorescence in situ hybridization (FISH) to human chromosome 19q13.3, where the CD33 gene is also located.
Calorimetric study of peptide-phospholipid interactions: the glucagon-dimyristoylphosphatidylcholine complex (1981)

The isothermal enthalpy of reaction glucagon with dimyristoylphosphatidylcholine is found to be large and markedly temperature dependent, changing from -150 kcal/mol of glucagon at 25 degrees C to + 80 kcal/mol of glucagon at 23 degrees C. The observed enthalpy is shown to arise mainly from the glucagon-induced alteration of the distribution of the phospholipid between gel and liquid crystalline phases. The reaction is accompanied by a large change in the apparent heat capacity around the phase transition temperature of the pure lipid which explains the small variation of the free energy of binding with temperature despite the large changes in enthalpy. The equilibrium binding constant calculated from the enthalpy as a function of lipid-peptide ratio is in good agreement with that previously found from fluorescence titrations, but the number of lipid molecules bound per glucagon molecule at 25 degrees C is increased from 20 to 50, suggesting that glucagon can bind to 50 lipid molecules but that only 20 of these are close enough to affect the fluorescence of the hormone. Differential scanning calorimetry of dimyristoylphosphatidylcholine in the presence of glucagon shows a transition curve composed of two components. The major component, corresponding to 80% of the enthalpy change, is centered at 26.1 degrees C and has a cooperative unit of 45 lipid molecules. The total enthalpy change for the transition in the presence of glucagon is only +3.2 kcal/mol, compared with +4.8 kcal/mol for the pure lipid.
The gene coding for a major tumor rejection antigen of tumor P815 is identical to the normal gene of syngeneic DBA/2 mice. (1991)

We showed previously that mouse mastocytoma P815 expresses several distinct antigens that are recognized by cytolytic T lymphocytes (CTL) of syngeneic DBA/2 mice. Antigens P815A and P815B are usually lost jointly and are targets for immune rejection responses in vivo. We used a cosmid library and a CTL stimulation assay to obtain transfectants expressing tumor rejection antigen P815A. From these transfectants we retrieved gene P1A which transferred the expression of both P815A and B. This gene is unrelated to three previously isolated genes coding for tum-antigens. It encodes a putative protein of 224 amino acids which contains two highly acidic domains showing homology with similar regions of nuclear proteins. The P1A gene expressed by tumor P815 is completely identical to the gene present in normal DBA/2 cells. Expression of the gene was tested by Northern blots. Cells from liver, spleen, and a number of mast cell lines were negative, but mast cell line L138.8A produced a high level of P1A message and was lysed by CTL directed against antigens P815A and B. We conclude that major tumor rejection antigens of P815 are encoded by a gene showing little or no expression in most normal cells of adult mice.