gebhart/patrepeval huggingface dataset:
Identification of a Membrane-Spanning Domain of the Thiol-Activated Pore-Forming Toxin Clostridium perfringens Perfringolysin O:  An α-Helical to β-Sheet Transition Identified by Fluorescence Spectroscopy (1998)

Clostridium perfringens perfringolysin O (PFO or theta-toxin) is a cytolytic toxin that binds to cholesterol-containing membranes and then self-associates to spontaneously form aqueous pores of varying size in the bilayer. In this study, a membrane-spanning domain has been identified in PFO by a combination of fluorescence spectroscopic methods using the fluorescent dye N, N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1, 3-diazolyl)ethylenediamine (NBD) whose emission properties are sensitive to water. PFO was substituted with a single cysteine at most of the residues between amino acids K189 and N218, and then each cysteine was modified with NBD. Each purified NBD-labeled PFO was then bound to membranes, and the probe's environment was ascertained by measuring its fluorescence lifetime, emission intensity, and collisional quenching with either aqueous (iodide ions) or nonaqueous (nitroxide-labeled phospholipids) quenchers. Lifetime and intensity measurements revealed that the amino acid side chains in this region of the membrane-bound PFO polypeptide alternated between being in an aqueous or a nonaqueous environment. This pattern indicates that this portion of the membrane-bound PFO spans the membrane in an antiparallel beta-sheet conformation. The alternating exposure of these residues to the hydrophobic interior of the bilayer was demonstrated by their susceptibility to quenching by nitroxide moieties attached to phospholipid acyl chains. Residues K189-N218 therefore form a two-stranded, amphipathic beta-sheet in the membrane-bound PFO that creates a stable interface between the pore and the membrane. This same region packs as three short alpha-helices in the soluble, monomeric form of PFO, and therefore, the cholesterol-dependent conversion of PFO to a membrane-bound oligomer involves a major structural transition in which three alpha-helices unfold to form a membrane-spanning amphipathic beta-sheet.
Formation of FVIIa-Antithrombin Complexes After Administration of rFVIIa to Hemophilia Patients. (2009)

Abstract Abstract 1295 Poster Board I-317 Introduction Recent animal studies suggest that measurable amounts of factor VIIa and antithrombin (AT) complexes are formed and accumulate following rFVIIa administration. The in vivo rate of inhibition has been reported to be faster than the un-stimulated in vitro reaction between AT and free rFVIIa and of the same order of magnitude as the rate determined in the presence of tissue factor. To study the impact of AT inhibition on the elimination of rFVIIa in humans, we measured the pharmacokinetics (PK) of rFVIIa and rFVIIa-AT complex formation in 10 hemophilia A or B patients. Patients and Methods The PK of single-dose rFVIIa 90 μg/kg (Novo Nordisk A/S) was evaluated in 10 severe FVIII- or FIX-deficient patients in a non-bleeding state. The plasma concentrations of FVIIa activity (FVII:C), FVII antigen (FVII:Ag), FVIIa-AT, D-dimer and F1+2 fragment were determined immediately before, and at 0.5, 1, 2, 4 and 6 hours following rFVIIa dosing. Results Significant amounts of FVIIa–AT complex were formed in vivo after rFVIIa administration, and reached a maximum of 5.4 ± 0.8 nmol/L [mean ±SD] at 2 hours following rFVIIa administration and declined to 4.4 ± 0.9 nmol/L at 6 hours, as compared to 0.1 ± 0.05 nmol/L at baseline. While the FVII:C PK data in this study were consistent with previous data, there was greater total body clearance (Cltot), a larger volume of distribution (Vdss) and a shorter plasma half-life (T1/2) of FVII:C relative to FVII:Ag (Table). No change in D-dimer was observed after the administration of rFVIIa, while a slight increase in F1+2 fragment levels to 258 ± 73 pmol/L was measured 4 hours after rFVIIa dosing, as compared to 141 ± 45 pmol/L at baseline. Conclusion A significant divergence between the clearance of rFVIIa, as determined by either FVII:C or FVII:Ag measurements, can be accounted for by AT complex formation. Inhibition by AT appears thus to have a significant impact on the elimination of FVII:C activity from the circulation when rFVIIa is administered at a therapeutic dose. Similar to animal data, the formation of the FVIIa-AT complexes in vivo was faster than anticipated from in vitro studies, indicating that the exposure to the vessel wall stimulates the FVIIa inhibition by AT. Analyses of coagulation parameters did not indicate induction of systemic coagulation. Disclosures Ezban: NovoNordisk A/S: Employment. Pelzer:NovoNordisk: Employment. Agerso:NovoNordisk: Employment. Petersen:NovoNordisk: Employment. Hedner:NovoNordisk: Employment. Carr:NovoNordisk: Employment.
Synthesis and Pharmacology of 2,5-Disubstituted 1,3,4-Oxadiazoles (1981)

Regional Research Laboratory, Hyderabad-500 009 (A. P.) Department of Pharmacology, Beth G. S. Medical College, Bombay-400 012 <em>Manuscript received 14 August 1980, accepted 28 January 1981</em> A series of new 2,5-disubstituted 1,3,4-oxadiazoles carrying 1,2-diarylethyl /aryloxyalkyl moieties at 2-position and phenyl, amino, mercapto, thioacetic acid or ethyl thioacetate groups at 5 position were synthesised and evaluated for their pharmacol ogical activity. Some members exhibited mild to strong antiinflammatory and CNS depressant action in experimental animals.
Fallen conductor accidents: The challenge to improve safety (1992)

In the present study, eleven compounds (1-11) including nine alkaloids (1-9), one triterpenoid saponin (10) and one formamide (11) were isolated from <i>Talaromyces sp.</i> LGT-2, an endophytic fungus from <i>Tripterygium wilfordi</i>. Their structures were determined based on NMR and ESI-MS spectral data, as well as comparing previous literature data. This is the first report of the isolation of alkaloids (1-9) from <i>Talaromyces</i> genus. In the next step, all compounds were screened for their anti-monoamine oxidase, anti-acetylcholinesterase, antibacterial and antitumor activities. Compound 11 showed moderate anti-monoamine oxidase activity with IC<sub>50</sub> value of 61 μM; compounds 3, 4, 8 showed weaker anti-acetylcholinesterase activity; compounds 1, 3, 4, 7, 8, 9 showed moderate antibacterial activities; compounds 7, 8, 9 showed cytotoxicity against B16 cancer cell line with inhibitory rate of 86%, 82%, 78%, respectively, at the concentration of 500 μg/mL.
[Rule of antibody structure: the primary structure of a human monoclonal IgA1-immunoglobulin (myeloma protein Tro), V. The arrangement of the tryptic peptides and a discussion of the complete primary structure of the H-chain (author's transl)]. (1978)

This communication deals with the sequence work done with tryptic and chymotryptic peptides and some cyanogen bromide splitting products. With these peptides, and if necessary with their splitting peptides, the whole primary structure of the alpha1-H-chain of myeloma protein Tro is established. The position of the amides is determined by electrophoresis and digestion with aminopeptidase M. The alpha1-chain Tro comprises 475 amino acid residues. Because of its specific exchanges and deletions the variable part of alpha1-chain Tro belongs to subgroup III of variable parts of H-chains. The switch from the variable to the constant part occurs at position 119/120 and is analogous to other chains which have been sequenced up to now. The large number of cysteine residues in the alpha-chain which may influence the tertiary structure, especially in the hinge and the subsequent CH2-region, is noteworthy. Furthermore, myeloma protein Tro is compared with the other alpha1-chain Bur[5] sequenced in the meantime, and protein But[6], which is an IgA2 molecule of the allotype A2m(2).
Faggot cells in a non-promyelocytic acute myeloid leukemia (2014)

Department of Hematology, Postgraduate Institute of Medical Education and Research, Level 5, Research Block A, Sector 12,Chandigarh 160012, India* Corresponding author. Tel.: +91 88 72016123; fax: +91 172 2744401 AE doctusharsehgal@yahoo.co.in (T.shegal) AEsharma.prashant@pgimer.edu.in (P.Sharma) AE varmaneelam@yahoo.com (N.Varma) AE Accepted for publication 18 April 2014Hematol Oncol Stem Cell Ther 2014; xx(xx): xxx–xxxa 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.DOI: http://dx.doi.org/10.1016/j.hemonc.2014.04.003
Short-range FMCW monopulse radar for hand-gesture sensing (2015)

Intelligent driver assistance systems have become important in the automotive industry. One key element of such systems is a smart user interface that tracks and recognizes drivers' hand gestures. Hand gesture sensing using traditional computer vision techniques is challenging because of wide variations in lighting conditions, e.g. inside a car. A short-range radar device can provide additional information, including the location and instantaneous radial velocity of moving objects. We describe a novel end-to-end (hardware, interface, and software) short-range FMCW radar-based system designed to effectively sense dynamic hand gestures. We provide an effective method for selecting the parameters of the FMCW waveform and for jointly calibrating the radar system with a depth sensor. Finally, we demonstrate that our system guarantees reliable and robust performance.
Human papillomavirus infection and cervical neoplasia: new perspectives. (1984)

This review addresses several problems associated with human papillomavirus (HPV) infection of the cervix and lower female genital tract. These include the definition of HPV infection and its distinction from HPV-associated neoplasia, the distinction of HPV infection from reactive epithelial changes induced by other infections, and the transmission of HPV infection via the male partner. The available evidence indicates that there are two distinct intraepithelial processes in the cervix associated with HPV. One is the classical condyloma and its counterpart in immature epithelium, atypical immature metaplasia. The other is intraepithelial neoplasia, which, like classical infection, may be mature [cervical intraepithelial neoplasia (CIN) with koilocytosis] or immature (high grade CIN or carcinoma in situ). Molecular hybridization studies indicate that HPVs 6 and 11 are most commonly detected in the former, whereas HPVs 16 and 18 DNA are most common in the latter and in invasive cancer. From the clinical standpoint the most important distinction is between HPV-related disease (condyloma or CIN) and reactive changes associated with other pathogens, such as Chlamydia. The former should be removed from the cervix, whereas the latter should be treated medically or followed. It is stressed that therapy should not hinge upon the histological distinction of HPV infection from neoplasia and that all lesions should be removed, by conservative means if possible. This is underscored by the fact that a high proportion of CIN lesions contain areas identical to condyloma and that lesions with deep endocervical canal involvement, including those with features suggesting condyloma, should be treated by cone biopsy to exclude the presence of invasive cancer. Histological classifications for nonneoplastic, HPV-infected, and neoplastic epithelium are proposed. The management of the male partner is still unsettled. However, a large proportion of male partners of these patients have penile lesions and should be included in diagnostic and therapeutic protocols of women with genital HPV infections or neoplasms.
Nonlinear polarization description of phase-locked pulse-pair spectroscopy (1992)

The recently demonstrated technique of optically phase-locked pulse-pair (PLPP) excited spontaneous emission is described by a third-order perturbative density matrix approach. A nonlinear polarization description shows how PLPP spectroscopy depends on all the relevant material dephasing time scales. The time and frequency integrated resonance spontaneous emission consists entirely of resonance fluorescence, and is derived exclusively from excited-state population decay terms, i.e., diagonal second-order density-matrix elements. These third-order polarization results are proportional to the previously derived linear polarization expressions found to describe the observed PLPP I2 vapor emission. The nonlinear treatment allows a comparison of this technique to other forms of ultrafast pump–probe spectroscopies such as transient absorption and photon echo techniques. The role of impulsively prepared coherences is clearly described by this analysis. The effect of pulse duration, relative to material dephasing times, is explored for relaxation given by the optical Bloch equations. The most significant differences between a linear and nonlinear polarization treatment occur for pulse durations greater than the optical dephasing time or when excited state population and coherence decays are of the order of rovibrational periods. A fluorescence line narrowing effect, due to short pulse excitation, is predicted.
Lanthanide gallate perovskite-type substrates for epitaxial, high-T c superconducting Ba 2 YCu 3 O 7-δ films (1990)

Previous studies had indicated promising use of lanthanide gallate perovskite-type substrates for the deposition of epitaxial, high-T <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</inf> superconducting Ba <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> YCu <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7-δ</inf> (BYCO) films. They were also found to have moderate dielectric constants (∼25 compared to ∼277 for SrTiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> ). This study was undertaken to further explore the use of LaGaO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> , NdGaO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> , SrTiO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> , MgO, and Y-stabilized ZrO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> substrates, prepared from single-crystal boules grown by several suppliers using the Czochralski method. Films were prepared by cylindrical magnetron sputtering and laser ablation. Substrate evaluations included measurement of dielectric constant and loss, thermal expansion, and mechanical hardness and toughness. In addition to their moderate dielectric constants, they were found to have satisfactory mechanical properties, except for the twinning tendency of LaGaO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> . Lattice mismatch strains were calculated for orthorhombic BYCO films on a number of substrates. NdGaO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> was found to have the best lattice match with BYCO, and is now available twin-free.
Tunable Electrical Conductivity of Individual Graphene Oxide Sheets Reduced at “Low” Temperatures (2008)

Step-by-step controllable thermal reduction of individual graphene oxide sheets, incorporated into multiterminal field effect devices, was carried out at low temperatures (125-240 degrees C) with simultaneous electrical measurements. Symmetric hysteresis-free ambipolar (electron- and hole-type) gate dependences were observed as soon as the first measurable resistance was reached. The conductivity of each of the fabricated devices depended on the level of reduction (was increased more than 10(6) times as reduction progressed), strength of the external electrical field, density of the transport current, and temperature.
Creation of a standardized geometry of the human nasal cavity (2009)

A novel, standardized geometry of the human nasal cavity was created by aligning and processing 30 sets of computed tomography (CT) scans of nasal airways of healthy subjects. Digital three-dimensional (3-D) geometries of the 60 single human nasal cavities (30 right and 30 mirrored left cavities) were generated from the CT scans and measurements of physical parameters of each single nasal cavity were performed. A methodology was developed to scale, orient, and align the nasal geometries, after which 2-D digital coronal cross-sectional slices were generated. With the use of an innovative image processing algorithm, median cross-sectional geometries were created to match median physical parameters while retaining the unique geometric features of the human nasal cavity. From these idealized 2-D images, an original 3-D standardized median human nasal cavity was created. This new standardized geometry was compared against the original geometries of all subjects as well as limited existing data from the literature. The new model has potential for use as a geometric standard in future experimental and numerical studies of deposition of inhaled aerosols, as well as for use as a reference during diagnosis of unhealthy patients. The specific procedure developed could also be applied to build standard nasal geometries for different identifiable groups within the larger population.
Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis (2010)

The ADA and the EASD recently published a consensus statement for the medical management of hyperglycaemia in patients with type 2 diabetes. The authors advocate initial treatment with metformin monotherapy and lifestyle modification, followed by addition of basal insulin or a sulfonylurea if glycaemic goals are not met (tier 1 recommendations). All other glucose-lowering therapies are relegated to a secondary (tier 2) status and only recommended for selected clinical settings. In our view, this algorithm does not offer physicians and patients the appropriate selection of options to individualise and optimise care with a view to sustained control of blood glucose and reduction both of diabetes complications and cardiovascular risk. This paper critically assesses the basis of the ADA/EASD algorithm and the resulting tiers of treatment options.
Structure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224 (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure determination, conformational analysis, chemical stability studies, and antitumor evaluation of the cryptophycins. Isolation of 18 new analogs from Nostoc sp. strain GSV 224Trimurtulu Golakoti, Junichi Ogino, Carl E. Heltzel, Trang Le Husebo, Craig M. Jensen, Linda K. Larsen, Gregory M. L. Patterson, Richard E. Moore, Susan L. Mooberry, Thomas H. Corbett, and Frederick A. ValerioteCite this: J. Am. Chem. Soc. 1995, 117, 49, 12030–12049Publication Date (Print):December 1, 1995Publication History Published online1 May 2002Published inissue 1 December 1995https://pubs.acs.org/doi/10.1021/ja00154a002https://doi.org/10.1021/ja00154a002research-articleACS PublicationsRequest reuse permissionsArticle Views1107Altmetric-Citations166LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses (2018)

T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4<sup>+</sup> T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease. (1994)

Chronic and acute graft-versus-host disease (cGVHD and aGVHD) result from donor cells responding to host disparate MHC alleles. In cGVHD (H-2d-->H-2bd), heightened polyclonal immunoglobulin production is due to the interaction of donor allospecific helper T cells (Th) and the host B cells. In vivo administration of antibody to the ligand for CD40, gp39, blocked cGVHD-induced serum anti-DNA autoantibodies, IgE production, spontaneous immunoglobulin production in vitro, and associated splenomegaly. Antibody production remained inhibited for extended periods of time after termination of anti-gp39 administration. Antiallogeneic CTL responses induced in a GVHD were also prevented by the in vivo administration of anti-gp39 as was the associated splenomegaly. These data suggest that CD40-gp39 interactions are critical in GVHD and that CD40-gp39 may be a valuable ligand-receptor pair for targeting immunotherapeutic agents to control GVHD.
Control of threshold voltage in ZnO-based oxide thin film transistors (2008)

We investigated the feasibility of controlling the threshold voltage (Vth) by adjusting the thickness of the active layer (tactive) rather than by conventional chemical doping in indium-gallium-zinc oxide (IGZO) transistors with an inverted staggered structure. The value of Vth of the IGZO transistor was linearly modulated from −15.3±1.6to−0.1±0.21V by reducing tactive without any significant change in the field-effect mobility (μFE), subthreshold gate swing, or Ion∕off ratio. The free electron density extracted from the relationship between tactive and Vth was 1.9×1017cm−3, which was consistent with the value of 1.5×1017cm−3 obtained from the C-V measurement for the 30-nm-thick IGZO films. The slight increase in the μFE with increasing tactive, which was in contradiction with the behavior of the corresponding amorphous Si transistor, was explained by the anomalous behavior of the source/drain contact resistance.