gebhart/patrepeval huggingface dataset:
Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K + channels (1998)

Drosophila genes reaper, grim, and head-involution-defective (hid) induce apoptosis in several cellular contexts. N-terminal sequences of these proteins are highly conserved and are similar to N-terminal inactivation domains of voltage-gated potassium (K+) channels. Synthetic Reaper and Grim N terminus peptides induced fast inactivation of Shaker-type K+ channels when applied to the cytoplasmic side of the channel that was qualitatively similar to the inactivation produced by other K+ channel inactivation particles. Mutations that reduce the apoptotic activity of Reaper also reduced the synthetic peptide's ability to induce channel inactivation, indicating that K+ channel inactivation correlated with apoptotic activity. Coexpression of Reaper RNA or direct injection of full length Reaper protein caused near irreversible block of the K+ channels. These results suggest that Reaper and Grim may participate in initiating apoptosis by stably blocking K+ channels.
Structural and electronic properties of glassyGeSe2surfaces (2000)

We report first-principles structural models of surfaces of glassy ${\mathrm{GeSe}}_{2}$ $(g\ensuremath{-}{\mathrm{GeSe}}_{2}).$ The structural properties of bulk and surface $g\ensuremath{-}{\mathrm{GeSe}}_{2}$ are compared with recent experimental data. The first diffraction peaks in the partial structure factors are accurately reproduced in both the surface and bulk models. We also examine the transition of the local bonding environment from the bulk to the surface. The surface reconstruction involves creation of several edge-sharing tetrahedra and electronic states are easily delocalized through rings formed in the reconstruction.
Enhanced resolution of glycosylphosphatidylinositol‐anchored and transmembrane proteins from the lipid‐rich myelin membrane by two‐dimensional gel electrophoresis (2003)

Two-dimensional gel electrophoresis (2-DE) has become a powerful and widely used technique for proteomic analyses. However, the limited ability of 2-DE to resolve transmembrane and glycosylphosphatidylinositol (GPI)-anchored proteins has slowed the identification of proteins from membrane-rich biological samples. Myelin is an unusually lipid-rich membrane with relatively few major proteins but many quantitatively minor proteins, most of which have an unknown identity and/or function. The goal of this study was to identify the optimal conditions of 2-DE for the separation of myelin proteins. We have identified two detergents, the nonionic n-dodecyl beta-D-maltoside and the zwitterionic amidosulfobetaine ASB-14, that are more effective in solubilizing myelin proteins than the commonly used zwitterionic detergent 3-[(3-cholamidopropyl)- dimethylammonio]-1-propanesulfonate (CHAPS). These detergents significantly enhance the solubility of both transmembrane (e.g., the highly hydrophobic and multiply acylated myelin proteolipid protein) and GPI-anchored (e.g., contactin and neuronal cell adhesion molecule) myelin proteins and enable their resolution by 2-DE. We conclude that these detergents are effective tools for the 2-DE analysis of myelin, and that they may be more generally useful for the analysis of membrane-rich biological samples.
Recent Progress in Polymer Solar Cells: Manipulation of Polymer:Fullerene Morphology and the Formation of Efficient Inverted Polymer Solar Cells (2009)

Abstract Polymer morphology has proven to be extremely important in determining the optoelectronic properties in polymer‐based devices. The understanding and manipulation of polymer morphology has been the focus of electronic and optoelectronic polymer‐device research. In this article, recent advances in the understanding and controlling of polymer morphology are reviewed with respect to the solvent selection and various annealing processes. We also review the mixed‐solvent effects on the dynamics of film evolution in selected polymer‐blend systems, which facilitate the formation of optimal percolation paths and therefore provide a simple approach to improve photovoltaic performance. Recently, the occurrence of vertical phase separation has been found in some polymer:fullerene bulk heterojunctions. The origin and applications of this inhomogeneous distribution of the polymer donor and fullerene acceptor are addressed. The current status and device physics of the inverted structure solar cells is also reviewed, including the advantage of utilizing the spontaneous vertical phase separation, which provides a promising alternative to the conventional structure for obtaining higher device performance.
Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-α-glucosidase (1999)

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid alpha-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies.
Prothrombin Determination by Means of a Chromogenic Peptide Substrate (1976)

A two stage method to determine prothrombin with the chromogenic peptide substrate benzoyl-phe-val-arg-p-nitroanilide has been worked out. Citrated plasma (10 mul) was diluted in 600 mul tris buffer, pH 8.2, ionic strength 0.18 and activated with 250 mul of a commercial rabbit brain-lung thromboplastin. After 325 s incubation at 37 degrees C 200 mul of a 1 mM solution of the chromogenic substrate was added and the increase in absorbance was recorded in a LKB-Beckman 8600 enzyme analyzer. A reading time of 1 minute (including a delay of 20 s) was used which permitted 55 analyses per hour to be carried out. An approximate linear relationship was found between delta A/min and dilutions of normal plasma in prothrombin deficient plasma. The method is insensitive to variations of factors V, VII and X. Less than 10% or normal plasma was needed to "normalize" plasmas deficient in factor V or VII or X. A group of 99 dicoumarol treated patients and 23 normal subjects has been investigated using the present method and compared with a factor II-VII-X determination method. A correlation coefficient of 0.95 was found.
Bismuth Aluminate: A New High-TCLead-Free Piezo-/ferroelectric (2007)

Ferroelectric materials, which have a reversible spontaneous polarization and generate an electric potential when subjected to a mechanical stress (piezoelectricity), have applications in nonvolatile random access memory devices and micro-electromechanical systems. For such applications, materials that remain ferroelectric up to high temperatures are desired. Bismuth aluminate has been predicted to be one such material. We present herein the first characterization of the dielectric, ferroelectric, and piezoelectric properties of the ceramic BiAlO3 synthesized by the high-pressure method. It is demonstrated that BiAlO3 is indeed a lead-free ferroelectric with a Curie temperature TC > 520 °C, a piezoelectric coefficient d33 = 28 pC/N, and a room-temperature remnant polarization Pr = 9.5 μC/cm2. Pr increases with temperature, reaching 26.7 μC/cm2 at 225 °C.
Understanding the factors involved in determining the bioburdens of surgical masks (2019)

Multiple factors influence SM bioburdens. Mask B showed the lowest bioburden and best protection effects. Mask C is not recommended to be used, especially considering that surgeons do not wash the cloth masks daily. Unnecessary talking during operation is not recommended, and washing the face before surgery is not strictly necessary.
Synthesis and assembly of hepatitis A virus-specific proteins in BS-C-1 cells (1993)

To determine the mechanism for the delayed and inefficient replication of the picornavirus hepatitis A virus in cell culture, we studied the kinetics of synthesis and assembly of virus-specific proteins by metabolic labeling of infected BS-C-1 cells with L-[35S]methionine and L-[35S]cysteine. Sedimentation, electrophoresis, and autoradiography revealed the presence of virions, provirions, procapsids, and 14S (pentameric) subunits. Virions and provirions contained VP1, VP0, VP2, and VP3; procapsids contained VP1, VP0, and VP3; and pentamers contained PX, VP0, and VP3, as previously shown by immunoblotting (D.A. Anderson and B.C. Ross, J. Virol. 64:5284-5289, 1990). Under single-cycle growth conditions label was found in 14S subunits immediately after labeling from 15 to 18 h postinfection (p.i.); however, a proportion of labeled polyprotein was not cleaved and assembled into pentamers for a further 18 h. When analyzed at 72 h p.i., incorporation of label which flowed into virions was detected from 3 h p.i., with maximal uptake levels being observed from 12 to 15 h p.i. Viral antigen, infectious virus, and viral RNA were determined in parallel, with coincident peaks in these variables being observed 12 h after the period of maximum label uptake. It was also found that the lag between the synthesis of the viral polyprotein and assembly of viral particles was the same after labeling from either 12 to 15 or 27 to 30 h p.i. despite increased levels of viral RNA during this period, suggesting that factors additional to the level of RNA are involved in the restriction of viral replication. Sedimentation and immunoblot analysis revealed an additional protein of approximately 100 kDa containing both VP1- and VP2-reactive sequences and sedimenting slightly more slowly than 14S pentamers, which may represent intact P12A assembled into pentamers as has been reported for the P1 of some other picornaviruses (S. McGregor and R. R. Rueckert, J. Virol. 21:548-553, 1977). The results of this study suggest that cleavage of the hepatitis A virus polyprotein to produce pentamers is protracted (though not rate limiting) early in infection, while the assembly of pentamers into higher structures is a rapid process once sufficient viral RNA is produced for encapsidation.
Gadd45β mediates the protective effects of CD40 costimulation against Fas-induced apoptosis (2003)

In B lymphocytes, induction of apoptosis or programmed cell death (PCD) by Fas (CD95/APO-1) is suppressed by the triggering of CD40. This suppression controls various aspects of the humoral immune response, including antibody affinity maturation. The opposing effects of these receptors are also crucial to B-cell homeostasis, autoimmune disease, and cancer. Cytoprotection by CD40 involves activation of protective genes mediated by NF-kappa B transcription factors; however, its basis remains poorly understood. Here, we report that, in B cells, Gadd45 beta is induced by CD40 through a mechanism that requires NF-kappa B and that this induction suppresses Fas-mediated killing. Importantly, up-regulation of Gadd45 beta by CD40 precedes Fas-induced caspase activation, as well as up-regulation of other NF-kappa B-controlled inhibitors of apoptosis such as Bcl-xL and c-FLIPL. In the presence of Gadd45 beta, the Fas-induced apoptotic cascade is halted at mitochondria. However, in contrast to Bcl-xL, Gadd45 beta is unable to hamper the "intrinsic" pathway for apoptosis and in fact appears to block Fas cytotoxicity herein by suppressing a mitochondria-targeting mechanism activated by this receptor. These findings identify Gadd45 beta as a critical mediator of the prosurvival response to CD40 stimulation and provide important new insights into the apoptotic mechanism that is triggered by Fas in B cells.
Receptor binding studies disclose a novel class of high‐affinity inhibitors of the Escherichia coli FimH adhesin (2004)

Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl alpha-D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (Kd = 0.15 microM) than mannose (Kd = 2.3 microM). Exploration of the binding affinities of alpha- d-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.
A blinded, randomized clinical trial evaluating the efficacy and safety of lokivetmab compared to ciclosporin in client‐owned dogs with atopic dermatitis (2017)

Lokivetmab at a minimum monthly dose of 1 mg/kg provided quick onset (within one day) of a lasting effect in reducing pruritus and skin lesions with a good safety profile.
Association between Aurora‐A kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population (2007)

Aurora-A kinase is considered a potential cancer susceptibility gene that encodes a centrosome-associated, cell cycle-regulated serine/threonine kinase. We studied two single nucleotide polymorphisms (SNP) in the coding region of Aurora-A, 91T-to-A (F31I) and 169G-to-A (V57I). We studied the influence of these two polymorphisms on age of onset of hereditary nonpolyposis colorectal cancer (HNPCC). Genotyping of the Aurora-A polymorphisms was carried out on 125 Caucasian with mismatch repair (MMR) gene mutations with real-time pyrophosphate DNA sequencing. For the 91T-to-A polymorphism, we found that patients with HNPCC who were homozygous for the wild-type allele developed colorectal cancer (CRC) 7 years earlier than patients who were homozygous or heterozygous for the mutant allele. The169G-to-A polymorphism did not have a significant influence on risk for HNPCC. However, when we did haplotype analysis for these two polymorphisms, the 91A-169G haplotype was associated with protection from HNPCC at an earlier age.
Epidermal Growth Factor Receptor Signaling Synergizes with Hedgehog/GLI in Oncogenic Transformation via Activation of the MEK/ERK/JUN Pathway (2009)

Persistent activation of the Hedgehog (HH)/GLI signaling pathway has been implicated in the development of a number of human cancers. The GLI zinc finger transcription factors act at the end of the HH signaling cascade to control gene expression, and recent studies have shown that the activity of GLI proteins can be additionally modified by integration of distinct signals, such as the MEK/extracellular signal-regulated kinase (ERK) and phosphinositide-3 kinase (PI3K)/AKT pathway. However, little is known about the identity of the upstream activators of these HH/GLI interacting signaling pathways in cancer. Here, we provide evidence that integration of the HH/GLI and epidermal growth factor receptor (EGFR) pathway synergistically induces oncogenic transformation, which depends on EGFR-mediated activation of the RAS/RAF/MEK/ERK but not of the PI3K/AKT pathway. EGFR/MEK/ERK signaling induces JUN/activator protein 1 activation, which is essential for oncogenic transformation, in combination with the GLI activator forms GLI1 and GLI2. Furthermore, pharmacologic inhibition of EGFR and HH/GLI efficiently reduces growth of basal cell carcinoma (BCC) cell lines derived from mice with activated HH/GLI signaling. The results identify the synergistic integration of GLI activator function and EGFR signaling as a critical step in oncogenic transformation and provide a molecular basis for therapeutic opportunities relying on combined inhibition of the HH/GLI and EGFR/MEK/ERK/JUN pathway in BCC.
Preemptive Therapy of EBV-Related Lymphoproliferative Disease after Pediatric Haploidentical Stem Cell Transplantation (2007)

The treatment of Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell transplantation (HSCT) is still unsatisfactory. We conducted a prospective trial to evaluate the impact of routine EBV surveillance and preemptive treatment with the anti-CD20 monoclonal antibody rituximab on the development of PTLD in pediatric recipients of extensively T-cell depleted HSCT from an HLA-haploidentical relative. Twenty-seven patients were included in the surveillance program, 12 developed EBV DNA positivity, with 8 of 12 presenting with sustained viral DNA levels requiring treatment with rituximab. Treatment was well tolerated, and induced clearance of EBV DNA in all patients. However, 4/8 patients showed a new increase in EBV load, coincident with the emergence of CD20(-)/CD19(+) B cells in peripheral blood, accompanied by overt PTLD in 3 patients. The latter cleared PTLD after receiving donor EBV-specific cytotoxic T-lymphocytes (CTLs), and persist in remission at a median 30-month follow-up. EBV-specific T-cell frequency, undetectable at time of EBV DNA positivity, was restored by T-cell therapy to levels comparable with controls. We conclude that preemptive therapy with rituximab is safe, but only partly effective in haplo-HSCT recipients. Patients who progress to PTLD under rituximab treatment can be rescued permanently by infusion of EBV-specific CTLs.
Kerberos: an authentication service for computer networks (1994)

When using authentication based on cryptography, an attacker listening to the network gains no information that would enable it to falsely claim another's identity. Kerberos is the most commonly used example of this type of authentication technology. The authors concentrate on authentication for real-time, interactive services that are offered on computer networks. They use the term real-time loosely to mean that a client process is waiting for a response to a query or command so that it can display the results to the user, or otherwise continue performing its intended function. This class of services includes remote login, file system reads and writes, and information retrieval for applications like Mosaic.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Azaspirene:  A Novel Angiogenesis Inhibitor Containing a 1-Oxa-7-azaspiro[4.4]non-2-ene-4,6-dione Skeleton Produced by the Fungus Neosartorya sp. (2002)

[structure: see text] Azaspirene isolated from the fungus Neosartorya sp. is a novel angiogenesis inhibitor with a 1-oxa-7-azaspiro[4.4]non-2-ene-4,6-dione skeleton. Azaspirene inhibits the endothelial migration induced by vascular endothelial growth factor (ED100 = 27.1 microM).
Oligonucleotides in the treatment of leukemia (1994)

The use of synthetic oligonucleotides directed towards specific genes in the therapy of leukemias has evolved rapidly over the past 5 years to early clinical trials. Undoubtedly, use of these compounds for systemic therapy and bone marrow 'purging' will escalate. Such trials will be models for the treatment of many other malignant diseases and, indeed, non-malignant diseases which may be expected to respond to eradication of a specific gene function. We are currently at the threshold of a new era of therapy which holds the promise of totally transforming clinical medicine in the next decade.
Maternal Viral Genotypic Zidovudine Resistance and Infrequent Failure of Zidovudine Therapy to Prevent Perinatal Transmission of Human Immunodeficiency Virus Type 1 in Pediatric AIDS Clinical Trials Group Protocol 076 (1998)

Maternal samples were assessed from 96 women enrolled in Pediatric AIDS Clinical Trials Group protocol 076 to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) genotypic zidovudine resistance at entry, if zidovudine resistance developed on study, and the role of zidovudine resistance in vertical transmission of HIV-1 despite zidovudine therapy. Low and high levels of genotypic resistance were assessed by differential hybridization, oligoligation, or direct sequencing of plasma HIV-1 RNA for codons K70R and T215Y/F. None of the women had high-level genotypic resistance to zidovudine at study entry or delivery. For low-level zidovudine resistance, the 95% confidence intervals were 0.3%-6.8% for baseline prevalence and 0.3%-14% for delivery incidence. Low-level zidovudine resistance, adjusted for plasma viral RNA level at delivery, was not strongly associated with an increase in vertical transmission risk (odds ratio, 4.8; 95% confidence interval, 0.2-131; P = .35).
Clinical practice guidelines for the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting (2011)

ver the past two decades, the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure by mask has increased substantially for acutely ill patients. Initial case series and uncontrolled cohort studies that suggested benefit in selected patients 1-13 led to many randomized controlled trials (RCTs). Both thods of ventilation have been used in the setting of acute respiratory failure to avoid endotracheal intubation in different patient populations and settings, with variable success. [117][118][119][120][ ] In addition, how can these two modes of noninvasive ventilation be optimally applied in these settings?