gebhart/patrepeval huggingface dataset:
Identification of a new SCN5A mutation, D1840G, associated with the long QT syndrome (1998)

The long QT syndrome (LQT) is an inherited cardiac disorder that can cause sudden cardiac death among apparently healthy young individuals due to malignant ventricular arrhythmias. LQT was found to be caused by mutations in four genes LQT1, LQT2, LQT3 and LQT5, and linkage was reported for an additional locus, LQT4, on chromosome 4q25-27. We have studied a large (n=131) LQT-affected Jewish kindred and identified tight linkage between the LQT-affected status and LQT3 (lod score 6.13, with an estimated recombination fraction of zero). We identified a new point-mutation, A to G substitution at nucleotide 5519 of the SCN5A gene, changing the aspartate 1840 to glycine, D1840G. This is a non-conservative change of an amino acid completely conserved in sodium channels from Molusca to human. The mutation was identified in all affected individuals (n=23), and not identified in all the unaffected family members (n=40), and not in 200 chromosomes of healthy control individuals. The mutation was identified in 3/12 individuals with equivocal phenotype, thus, providing an accurate diagnostic tool for all family members. This mutation is currently being used in a cellular electrophysiological model, to characterize the function of the mutated sodium channel in this syndrome. Hum Mutat 12:72, 1998. © 1998 Wiley-Liss, Inc.
Sequence of cbh-1 gene of Humicola grisea var. thermoidea (1990)

Sequence of cbh-1 gene of Humicola grisea var. thermoidea Get access Maristella de Oliviera Azevedo, Maristella de Oliviera Azevedo Department of Genetics, The University of LeedsLeeds LS2 9JT, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Alan Radford Alan Radford Department of Genetics, The University of LeedsLeeds LS2 9JT, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 3, 11 February 1990, Page 668, https://doi.org/10.1093/nar/18.3.668 Published: 11 February 1990 Article history Accepted: 02 January 1990 Published: 11 February 1990
De Novo Design, Synthesis, and Characterization of Antimicrobial β-Peptides (2001)

beta-Peptides are a class of polyamides that have been demonstrated to adopt a variety of helical conformations. Recently, a series of amphiphilic L(+2) helical beta-peptides were designed, which were intended to mimic the overall physicochemical properties of a class of membrane-active antimicrobial peptides, including magainin and cecropin. Although these peptides showed potent antimicrobial activity, they also showed significant activity against human erythrocytes. Operating under the assumption that their lack of specificity arose from excessive hydrophobicity, two additional beta-peptides H-(beta(3)-HAla-beta(3)-HLys-beta(3)-HVal)(n)-NH(2) (n = 4, 5) were designed and synthesized. Both have high antimicrobial activities, but very low hemolytic potencies. The peptides bind in an L(+2) conformation to phospholipid vesicles, inducing leakage of entrapped small molecules. The peptides have a low affinity for membranes consisting of neutral phosphatidylcholine lipids, but bind avidly to vesicles containing 10 mol % of acidic phosphatidylserine lipids. Differences in vesicle leakage kinetics for the two peptides suggest that chain length could affect their mechanisms of disrupting cell membranes. Thus, insights gained from the study of variants of natural alpha-peptides have provided a useful guide for the design of nonnatural antimicrobial beta-peptides.
Isolation and Characterization of Desulfitobacterium dehalogenans gen. nov., sp. nov., an Anaerobic Bacterium Which Reductively Dechlorinates Chlorophenolic Compounds (1994)

An organism that is able to reductively ortho-dechlorinate 2,4-dichlorophenol and 3-chloro-4-hydroxyphenylacetate (3-Cl-4-OHPA) was isolated from a methanogenic lake sediment. This organism, an anaerobic, motile, Gram-type-positive, rod-shaped bacterium, grew in the presence of 0.1% yeast extract when pyruvate, lactate, formate, or hydrogen was used as the electron donor for reductive dehalogenation of 3-Cl-4-OHPA. Sulfite, thiosulfate, and sulfur were reduced to sulfide, nitrate was reduced to nitrite, and fumarate was reduced to succinate. Dissimilatory reduction of sulfate could not be demonstrated, and no adenylylsulfate reductase was detected with an immunoassay. The organism fermented two pyruvate molecules to one lactate molecule, one acetate molecule, and one carbon dioxide molecule. The pH and temperature optima for both growth and dechlorination of 3-Cl-4-OHPA were 7.5 and 38 degrees C, respectively. The doubling time under these conditions was approximately 3.5 h. On the basis of the results of a 16S rRNA analysis and the inability of the organism to use sulfate as an electron acceptor, strain JW/IU-DC1 is described as the type strain of the new taxon Desulfitobacterium dehalogenans gen. nov., sp. nov.
Supporting Informal Communication across Local and Distributed Communities (2002)

A new species, Lethe tengchongensis Lang sp. nov., from Tengchong County, Mts. Gaoligong, western Yunnan Province, SW China is described and illustrated.
<title>Kinetic models of tissue fusion processes</title> (1992)

Recent studies of tissue fusion (welding) processes have reported temperature ranges but have not carefully analyzed critical exposure time data. Electron microscopic (EM) studies suggest that the fusion process in blood vessels may be dominated by random re-entwinement of thermally dissociated adventitial collagen fibrils (Type I) during the end stage heating and early cooling phases. At the light microscopic level, this bonding process is reflected by the formation of an amorphous coagulum of thermally coagulated adventitial collagen at the anastomotic site. We have constructed a numerical model of the vessel welding process, assuming CO<SUB>2</SUB> laser impingement, and used it to simulate quantitative histologic data obtained from successful welds of rat femoral and canine brachial arteries (unpublished data). The model estimates smooth muscle and collagen damage based on kinetic thermal damage analysis and water loss boundaries as a function of irradiation beam parameters and heating time. Both heating and cooling phases are simulated. The results illustrate the importance of the damage kinetics and local heat transfer phenomena to the weld characteristics realized.
Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers. (1990)

A major goal of current hematopoiesis research is to develop in vitro methods suitable for the measurement and characterization of stem cells with long-term in vivo repopulating potential. Previous studies from several centers have suggested the presence in normal human or murine marrow of a population of very primitive cells that are biologically, physically, and pharmacologically different from cells detectable by short-term colony assays and that can give rise to the latter in long-term cultures (LTCs) containing a competent stromal cell layer. In this report, we show that such cultures can be used to provide a quantitative assay for human "LTC-initiating cells" based on an assessment of the number of clonogenic cells present after 5-8 weeks. Production of derivative clonogenic cells is shown to be absolutely dependent on the presence of a stromal cell feeder. When this requirement is met, the clonogenic cell output (determined by assessment of 5-week-old cultures) is linearly related to the input cell number over a wide range of cell concentrations. Using limiting dilution analysis techniques, we have established the frequency of LTC-initiating cells in normal human marrow to be approximately 1 per 2 X 10(4) cells and in a highly purified CD34-positive subpopulation to be approximately 1 per 50-100 cells. The proliferative capacity exhibited by individual LTC-initiating cells cultured under apparently identical culture conditions was found to be highly variable. Values for the number of clonogenic cells per LTC-initiating cell in 5-week-old cultures ranged from 1 to 30 (the average being 4) with similar levels being detected in positive 8-week-old cultures. Some LTC-initiating cells are multipotent as evidenced by their generation of erythroid as well as granulopoietic progeny. The availability of a system for quantitative analysis of the proliferative and differentiative behavior of this newly defined compartment of primitive human hematopoietic cells should facilitate future studies of specific genetic or microenvironmental parameters involved in the regulation of these cells.
Randomized controlled trials: who fails run-in? (2016)

ClinicalTrials.gov: NCT00153816 . Registered September 2005.
Configuration and Conformation of So-called Bis(alkylidenearylamines) (1969)

Abstract The proposed structures of the dimeric products obtained from aliphatic aldehydes and arylamines were reexamined by IR and NMR spectra. The 1,2,3,4-tetrahydroquinoline structure was ascertained in the case of acetaldehyde or propionaldehyde, and aldolic structure was confirmed in the case of n-butyraldehyde. It was observed that the latter readily isomerizes to the former type in the presence of acetic acid. Conformational analysis of a racemic pair of the former (IIIa–c: 2,4-disubstituted, IIId- 2,3,4-trisubstituted) indicated that two isomers of IIIa–c (one has 2-equatorial, 4-quasi-equatorial and the other 2-equatorial, 4-quasi-axial substituents) have a flattened half-chair conformation and two isomers of Hid (one has 2,3-diequatorial, 4-quasi-equatorial, and the other 2-equatorial, 3-axial, 4-quasi-axial substituents) have a more remarkably flattened half-chair, i. e. a nearly plane structure. The acylation of ring nitrogen enhanced this tendency, and one of the 1-acetyl derivatives of III was deduced to have a twist half-boat conformation.
Cardiac MRI of the normal and hypertrophied mouse heart (1998)

With the development of recent transgenic techniques, studies involving mice offer opportunities to increase understanding of cardiac disease. This provides motivation for the current study to perform noninvasive evaluation of the normal and hypertrophied mouse heart with MRI. By acquiring ECG and respiratory signals, the MR image acquisition was gated to both the cardiac and respiratory cycles. Combining a spin-warp imaging sequence with an RF surface coil resulted in short-axis images that allowed quantification of in vivo cardiac mass. Excellent agreement between MRI-determined (y) and postmortem heart weight (x) was obtained: y = 0.991x + 1.43 (r = 0.996). Isoproterenol, at 282 micromol/kg body weight (BW) and 573 micromol/kg BW, induced a dose-dependent increase in the ratio of heart weight to BW of 16.8 +/- 1.09% and 24.1 +/- 1.71%, respectively, which was accurately measured by MRI. These results demonstrate the ability of MRI to noninvasively monitor cardiac anatomy in the mouse.
Chirped multilayer coatings for broadband dispersion control in femtosecond lasers (1994)

Optical thin-film structures exhibiting high reflectivity and a nearly constant negative group-delay dispersion over frequency ranges as broad as 80 THz are presented. This attractive combination makes these coatings well suited for intracavity dispersion control in broadband femtosecond solid-state lasers. We address design issues and the principle of operation of these novel devices.
Preparation and biomedical applications of bispecific antibodies. (1985)

Bispecific antibodies are immunoglobulin molecules with two different antigen binding sites. They can be prepared either by chemical crosslinking of immunoglobulins with different antigen specificities or by reassortment of the polypeptide chains from two different immunoglobulins to produce hybrid molecules with dual specificity. None of the earlier methods for the preparation of bispecific antibodies assure molecular homogeneity without difficult purification procedures; recently, however, a facile and efficient method was developed which can yield pure bispecific antibodies from monoclonal antibody fragments. This new method avoids some of the problems encountered earlier by using arsenite as a dithiol complexing agent to prevent intramolecular disulfide formation and 5,5'-dithiobis (2-nitrobenzoic acid) as a thiol activating agent to effect the directed recombination of two different antibody half-molecules. Bispecific monoclonal antibodies thus obtained are useful heterobifunctional reagents on account of their ability to bind two different antigens in a uniquely defined spatial relationship. They have potential applications as agents for enzyme immobilization, in the assembly of enzyme electrodes and multienzyme complexes, as reagents for two-site and homogeneous immunoassays, as electron microscopy markers for subcellular structures, and as targeting agents for cytotoxic drugs. In many of these applications, bispecific monoclonal antibodies have fundamental advantages over the heterogeneous mixtures containing hybrid antibodies that were available in the past.
Hydrophobic monolithic aerogels by nanocasting polystyrene on amine-modified silica (2006)

We describe a three-dimensional core–shell structure where the core is the assembly of nanoparticles that comprises the skeletal framework of a typical silica aerogel, and the shell is polystyrene. Specifically, the mesoporous surfaces of silica were first modified with amines by co-gelation of tetramethylorthosilicate (TMOS) and 3-aminopropyltriethoxysilane (APTES). Next, styrene moieties were attached to the amines by reaction with p-chloromethylstyrene. Finally, dangling styrene moieties were crosslinked by a free-radical polymerization process initiated by AIBN and styrene, p-chloromethylstyrene or 2,3,4,5-pentafluorostyerene introduced in the mesopores. Polystyrene crosslinked aerogels are mechanically strong, lightweight (0.41–0.77 g cm−3), highly porous materials (they consist of ca. 63% empty space, with a BET surface areas in the range of 213–393 m2 g−1). Their thermal conductivity (0.041 W m−1 K−1) is comparable to that of glass wool. Hydrophobicity, however, is the property that sets the new material apart from analogous polyurea and epoxy crosslinked aerogels. The contact angles of water droplets on disks cut from larger monoliths are >120°. (By comparison, the contact angle with polyurea crosslinked aerogels is only ca. 60°.) Polystyrene crosslinked aerogel monoliths float on water indefinitely, while their polyurea counterparts absorb water and sink within minutes.
Mass spectrometric studies of impurities in silane and their effects on the electronic properties of hydrogenated amorphous silicon (1983)

The concentration of volatile impurities in silane (SiH4) and disilane (Si2H6) used to prepare hydrogenated amorphous silicon (a-Si:H) thin films by glow-discharge deposition has been measured by modulated molecular beam mass spectrometry with a sensitivity of 1 ppm. From dark conductivity measurements on these films the location of the Fermi energy EF was determined. The Fermi levels of a-Si:H films were progressively lower with increasing concentrations of chlorine-containing molecules (mostly HCl and SiH3Cl) in the silane, indicating that these species can act as weak p-type dopants in a-Si:H. Oxygen-containing species (mostly SiH3OSiH3) were also detected in silane. It is clear from these results that large variations in electronic properties of glow discharge a-Si:H can be attributed to differences in purity of silane used in the deposition.
Infrared-Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (IR-MALDI-MS) of Proteins Electroblotted onto Polymer Membranes After SDS-PAGE Separation (1996)

The feasibility of using matrix-assisted laser desorption mass spectrometry (MALDI-MS) for analysis of proteins electroblotted onto polymer substrates after a one dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) separation of a protein mixture has been reported recently [1–3]. In this paper, the current state-of-the-art is summarized and exemplified by focusing on some fundamental analytical aspects, such as the mass range accessible, the application to hydrophilic membranes, the sample consumption per laser shot, the compatibility with different matrices and different staining materials as well as the accuracy of mass determination.
Topical negative pressure therapy. (2003)

Topical negative pressure therapy (TNP) has been available for clinical use in wound management since the late 1990s. It has been shown to be of particular benefit for the treatment of chronic nonhealing wounds and has also recently been positively linked to wound bed preparation.
Arrested Protein Synthesis Increases Persister-Like Cell Formation (2013)

Biofilms are associated with a wide variety of bacterial infections and pose a serious problem in clinical medicine due to their inherent resilience to antibiotic treatment. Within biofilms, persister cells comprise a small bacterial subpopulation that exhibits multidrug tolerance to antibiotics without undergoing genetic change. The low frequency of persister cell formation makes it difficult to isolate and study persisters, and bacterial persistence is often attributed to a quiescent metabolic state induced by toxins that are regulated through toxin-antitoxin systems. Here we mimic toxins via chemical pretreatments to induce high levels of persistence (10 to 100%) from an initial population of 0.01%. Pretreatment of Escherichia coli with (i) rifampin, which halts transcription, (ii) tetracycline, which halts translation, and (iii) carbonyl cyanide m-chlorophenylhydrazone, which halts ATP synthesis, all increased persistence dramatically. Using these compounds, we demonstrate that bacterial persistence results from halted protein synthesis and from environmental cues.
RNA-Catalyzed RNA Polymerization: Accurate and General RNA-Templated Primer Extension (2001)

The RNA world hypothesis regarding the early evolution of life relies on the premise that some RNA sequences can catalyze RNA replication. In support of this conjecture, we describe here an RNA molecule that catalyzes the type of polymerization needed for RNA replication. The ribozyme uses nucleoside triphosphates and the coding information of an RNA template to extend an RNA primer by the successive addition of up to 14 nucleotides-more than a complete turn of an RNA helix. Its polymerization activity is general in terms of the sequence and the length of the primer and template RNAs, provided that the 3' terminus of the primer pairs with the template. Its polymerization is also quite accurate: when primers extended by 11 nucleotides were cloned and sequenced, 1088 of 1100 sequenced nucleotides matched the template.
Generation and Characterization of a Panel of Monoclonal Antibodies Against Distinct Epitopes of Human CD146 (2008)

Abstract CD146 (MUC18, Mel-CAM/MCAM) is a transmembrane protein, originally identified as a biomarker of melanoma, and plays an important role in cancer invasion and metastasis. Further studies revealed that CD146 as a novel endothelial marker was also involved in angiogenesis. Previous studies reported several anti-CD146 antibodies, such as MUC18, A32, S-endo1, and P1H12, showing different binding patterns to the endothelium of various types of blood vessels. To examine the possibility that antibodies targeting different epitopes on CD146 could have different behaviors, we generated a panel of anti-human CD146 monoclonal antibodies, named AA1-5 and AA7, by immunizing mice with human CD146 protein purified from HUVEC. Their specificity and binding affinity were intensively characterized using Western blotting, flow cytometry, and immunohistochemical assay. On the basis of epitope mapping, we divided the six monoclonal antibodies (MAb) into two groups, groups V1 and C2-2, corresponding to the different extracellular domains harboring these epitopes, the first IgV and the second IgC2 domains, respectively. Furthermore, owing to different epitopes, the two groups of antibodies behaved differentially in cellular and histological levels. Therefore, these anti-CD146 MAbs targeting different domains should be useful tools in studying the expression and function of human CD146.
Interleukin 1 Alpha (IL1A) Is a Novel Regulator of the Blood-Testis Barrier in the Rat1 (2007)

Throughout spermatogenesis, leptotene spermatocytes must traverse the blood-testis barrier (BTB) at stages VIII-XI to gain entry into the adluminal compartment for continued development. However, the mechanism underlying BTB restructuring remains somewhat elusive. In this study, interleukin 1 alpha (IL1A) was administered intratesticularly to adult rats in order to assess its effects on spermatogenesis. IL1A was shown to perturb Sertoli-germ cell adhesion, resulting in germ cell loss from approximately 50% of seminiferous tubules by 15 days posttreatment. Equally important, the functional integrity of the BTB was compromised when inulin-fluorescein isothiocyanate was detected in the adluminal compartment of the seminiferous epithelium following its administration via the jugular vein. Interestingly, IL1A did not affect the steady-state levels of proteins that confer BTB function, namely OCLN, CLDN1, F11R, TJP1, and CDH2. Instead, the localizations of OCLN, F11R, and TJP1 in the seminiferous epithelium were altered; these proteins appeared to move away from sites of cell-cell contact. Moreover, IL1A was shown to perturb the orderly arrangement of filamentous actin at the BTB and apical ectoplasmic specialization with distinct areas illustrating loss of actin filaments. Taken collectively, these results suggest that IL1A-induced BTB disruption is not mediated via the reduction of target protein levels. Instead, IL1A's primary cellular target appears to be the Sertoli cell actin cytoskeleton. It is possible that localized production of IL1A by Sertoli and/or germ cells in vivo results in BTB restructuring, and this may facilitate the movement of leptotene spermatocytes across the BTB.
Risk of selection bias in randomised trials (2015)

The risk of selection bias could not be ascertained for most trials due to poor reporting. Many trials which did provide details on the randomisation procedure were at risk of selection bias due to a poorly chosen randomisation methods. Techniques to reduce the risk of selection bias should be more widely implemented.