gebhart/patrepeval huggingface dataset:
SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein (2020)

The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.
A Genetic Method for Generating Drosophila Eyes Composed Exclusively of Mitotic Clones of a Single Genotype (1999)

The genetic analysis of a gene at a late developmental stage can be impeded if the gene is required at an earlier developmental stage. The construction of mosaic animals, particularly in Drosophila, has been a means to overcome this obstacle. However, the phenotypic analysis of mitotic clones is often complicated because standard methods for generating mitotic clones render mosaic tissues that are a composite of both mutant and phenotypically normal cells. We describe here a genetic method (called EGUF/hid) that uses both the GAL4/UAS and FLP/FRT systems to overcome this limitation for the Drosophila eye by producing genetically mosaic flies that are otherwise heterozygous but in which the eye is composed exclusively of cells homozygous for one of the five major chromosome arms. These eyes are nearly wild type in size, morphology, and physiology. Applications of this genetic method include phenotypic analysis of existing mutations and F(1) genetic screens to identify as yet unknown genes involved in the biology of the fly eye. We illustrate the utility of the method by applying it to lethal mutations in the synaptic transmission genes synaptotagmin and syntaxin.
Comparative Fibrinolytic Properties of Staphylokinase and Streptokinase in Animal Models of Venous Thrombosis (1991)

The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases (1992)

Biologically active soluble TNF-R are up-regulated in patients with rheumatic disease and are produced locally in the joints. Measurement of serum levels of TNF-R may be useful for monitoring of disease, and determination of SF levels could be of diagnostic value.
The Pregnane X Receptor: A Promiscuous Xenobiotic Receptor That Has Diverged during Evolution (2000)

Transcription of genes encoding cytochrome P450 3A (CYP3A) monooxygenases is induced by a variety of xenobiotics and natural steroids. There are marked differences in the compounds that induce CYP3A gene expression between species. Recently, the mouse and human pregnane X receptor (PXR) were shown to be activated by compounds that induce CYP3A expression. However, most studies of CYP3A regulation have been performed using rabbit and rat hepatocytes. Here, we report the cloning and characterization of PXR from these two species. PXR is remarkably divergent between species, with the rabbit, rat, and human receptors sharing only approximately 80% amino acid identity in their ligand-binding domains. This sequence divergence is reflected by marked pharmacological differences in PXR activation profiles. For example, the macrolide antibiotic rifampicin, the antidiabetic drug troglitazone, and the hypocholesterolemic drug SR12813 are efficacious activators of the human and rabbit PXR but have little activity on the rat and mouse PXR. Conversely, pregnane 16alpha-carbonitrile is a more potent activator of the rat and mouse PXR than the human and rabbit receptor. The activities of xenobiotics in PXR activation assays correlate well with their ability to induce CYP3A expression in primary hepatocytes. Through the use of a novel scintillation proximity binding assay, we demonstrate that many of the compounds that induce CYP3A expression bind directly to human PXR. These data establish PXR as a promiscuous xenobiotic receptor that has diverged during evolution.
Immunoglobulin G and bovine serum albumin streaming dielectrophoresis in a microfluidic device (2011)

Dielectrophoresis (DEP) has demonstrated to be a versatile tool to manipulate micro- and nanoparticles with applications for positioning, separation and fractionation. Recent developments of DEP have also shown that DEP can be used for the manipulation of biomolecules, such as DNA. Here, we focus on the manipulation of proteins using insulator-based dielectrophoresis (iDEP). We designed suitable post arrays in a microfluidic channel and use numerical simulations to calculate the electric field distribution as well as concentration of proteins according to a convection-diffusion model for both negative and positive DEP. Experimentally, we find DEP trapping of mainly protein aggregates in phosphate buffer. However, when adding a charged zwitterionic detergent, we observed DEP streamlining of immunoglobulin G (IgG) and bovine serum albumin (BSA). Our experimental observations are in excellent agreement with numerical simulations and indicate positive DEP behavior of IgG and BSA under the employed experimental conditions. Our results demonstrate DEP streaming of proteins in an iDEP device for the first time and indicate the potential of protein DEP for separation and fractionation.
Endowing Human Pancreatic Ribonuclease with Toxicity for Cancer Cells (2001)

Onconase is an amphibian protein that is now in Phase III clinical trials as a cancer chemotherapeutic. Human pancreatic ribonuclease (RNase 1) is homologous to Onconase but is not cytotoxic. Here, ERDD RNase 1, which is the L86E/N88R/G89D/R91D variant of RNase 1, is shown to have conformational stability and ribonucleolytic activity similar to that of the wild-type enzyme but > 10(3)-fold less affinity for the endogenous cytosolic ribonuclease inhibitor protein. Most significantly, ERDD RNase 1 is toxic to human leukemia cells. The addition of a non-native disulfide bond to ERDD RNase 1 not only increases the conformational stability of the enzyme but also increases its cytotoxicity such that its IC(50) value is only 8-fold greater than that of Onconase. Thus, only a few amino acid substitutions are necessary to make a human protein toxic to human cancer cells. This finding has significant implications for human cancer chemotherapy.
Concurrency Control and Recovery in Database Systems (1987)

This book is an introduction to the design and implementation of concurrency control and recovery mechanisms for transaction management in centralized and distributed database systems. Concurrency control and recovery have become increasingly important as businesses rely more and more heavily on their on-line data processing activities. For high performance, the system must maximize concurrency by multiprogramming transactions. But this can lead to interference between queries and updates, which concurrency control mechanisms must avoid. In addition, a satisfactory recovery system is necessary to ensure that inevitable transaction and database system failures do not corrupt the database.
Systemically Administered Bone Morphogenetic Protein-6 Restores Bone in Aged Ovariectomized Rats by Increasing Bone Formation and Suppressing Bone Resorption (2006)

Although recombinant human bone morphogenetic proteins (BMPs) are used locally for treating bone defects in humans, their systemic effect on bone augmentation has not been explored. We have previously demonstrated that demineralized bone (DB) from ovariectomized (OVX) rats cannot induce bone formation when implanted ectopically at the subcutaneous site. Here we showed in vitro that 17beta-estradiol (E2) specifically induced expression of Bmp6 mRNA in MC3T3-E1 preosteoblastic cells and that bone extracts from OVX rats lack BMPs. Next we demonstrated that 125I-BMP-6 administered systemically accumulated in the skeleton and also restored the osteoinductive capacity of ectopically implanted DB from OVX rats. BMP-6 applied systemically to aged OVX rats significantly increased bone volume and mechanical characteristics of both the trabecular and cortical bone, the osteoblast surface, serum osteocalcin and osteoprotegerin levels, and decreased the osteoclast surface, serum C-telopeptide, and interleukin-6. E2 was significantly less effective, and was not synergistic with BMP-6. Animals that discontinued BMP-6 therapy maintained bone mineral density gains for another 12 weeks. BMP-6 increased in vivo the bone expression of Acvr-1, Bmpr1b, Smad5, alkaline phosphatase, and collagen type I and decreased expression of Bmp3 and BMP antagonists, chordin and cerberus. These results show, for the first time, that systemically administered BMP-6 restores the bone inductive capacity, microarchitecture, and quality of the skeleton in osteoporotic rats.
Baroreflex Sensitivity: Measurement and Clinical Implications (2008)

Alterations of the baroreceptor-heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three "classic" methods: (i) the use of vasoactive drugs, particularly the alpha-adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure.
Low-pH Triggering of Human Metapneumovirus Fusion: Essential Residues and Importance in Entry (2008)

Human metapneumovirus (HMPV) is a significant respiratory pathogen classified in the Pneumovirinae subfamily of the paramyxovirus family. Recently, we demonstrated that HMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. In the present study, we examined the potential role of histidine protonation in HMPV F fusion and investigated the role of low pH in HMPV viral entry. Mutagenesis of the three ectodomain histidine residues of the HMPV F protein demonstrated that the mutation of a histidine in the heptad repeat B linker domain (H435) ablated fusion activity without altering cell surface expression or proteolytic processing significantly. Modeling of the HMPV F protein revealed several basic residues surrounding this histidine residue, and the mutation of these residues also reduced fusion activity. These results suggest that electrostatic repulsion in the heptad repeat B linker region may contribute to the triggering of HMPV F. In addition, we examined the effect of inhibitors of endosomal acidification or endocytosis on the entry of a recombinant green fluorescent protein-expressing HMPV. Interestingly, chemicals that raise the pH of endocytic vesicles resulted in a 30 to 50% decrease in HMPV infection, while the inhibitors of endocytosis reduced infection by as much as 90%. These data suggest that HMPV utilizes an endocytic entry mechanism, in contrast to what has been hypothesized for most paramyxoviruses. In addition, our results indicate that HMPV uses the low pH of the endocytic pathway to enhance infectivity, though the role of low pH likely differs from classically described mechanisms.
Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes (2004)

Abstract The intramolecular bromo‐amidation and the dibromination‐cyclisation of the N ‐acylcyclohex‐3‐en‐1‐amines 4, 8, 9, 11, 13, 14 , and 16 was studied in view of the synthesis of bicyclic amines that are of interest as building blocks and potential glycosidase inhibitors. The trifluoroacetamides 4, 9 , and 14 reacted with N ‐bromosuccinimide (NBS) in AcOH to give dihydro‐1,3‐oxazines in good yields. The stereoselectivity of the dibromination of the alkenes 8 and 9 depends on the nature of the protecting group, the reagent, and the reaction conditions. Br 2 in CH 2 Cl 2 transformed the alkenes 8 and 9 predominantly into diaxial trans , trans ‐dibromides. Bromination of 9 with PhMe 3 NBr 3 or with Br 2 in the presence of Et 4 NBr gave predominantly the diequatorial trans , cis ‐ 27 besides some trans , trans ‐ 28 . A similar bromination of the C(5) ‐substituted N ‐acyl‐4‐aminocyclohexenes 11, 13, 14 , and 16 with PhMe 3 NBr 3 was accompanied by intramolecular side reactions that were suppressed by the addition of excess Et 4 NBr. Under these conditions, 11 gave diastereoselectively trans ‐dibromides, while its reaction with Br 2 gave trans ‐dibromides along with the dihydrooxazinone 31 . Also the carbamate 13 reacted with PhMe 3 NBr 3 /Et 4 NBr selectively to the trans ‐dibromide 32 and with Br 2 to the trans ‐dibromides 32 and 33 , the dihydrooxazinone 34 , and the bicyclic ether 35 . Similarly, the trifluoroacetamide 14 provided the dibromide 36 (89%), while its reaction with Br 2 led to the dihydrooxazine 22 , and the dibromides 36 and 37 . The N ‐benzyl‐ N ‐Boc derivative 16 did not yield any dibromide; it reacted with PhMe 3 NBr 3 /Et 4 NBr to the dihydrooxazinone 38 , and with Br 2 to the oxazinone 38 and the bicyclic ether 39 . The high stereoselectivity of the bromination with PhMe 3 NBr 3 /Et 4 NBr suggests an anchimeric assistance of the NHR substituent. Deprotection, cyclisation, and carbamoylation transformed the dibromides 27, 29 , and 32 into the 7‐azanorbornanes 42, 49 , and 53 . The diols 45 and 57 were obtained from 42 and 53 via HBr elimination and stereoselective dihydroxylation; they proved weak inhibitors of several glycosidases. In no case could the formation of a bicyclic azetidine (6‐azabicyclo[3.1.1]heptane) from the dibromides 26 and 30 be observed.
Global Shifts in Protein Sumoylation in Response to Electrophile and Oxidative Stress (2004)

Human small ubiquitin-like modifier (sumo) proteins include sumo-1 and the less studied, nearly identical sumo-2 and sumo-3 proteins. Whereas the structurally related ubiquitin molecule targets proteins for degradation, sumo provides a distinct, yet poorly understood regulatory signal. Protein sumoylation is sensitive to diverse cellular stresses, yet the targets of sumoylation in stress are unknown. We studied protein sumoylation in HEK293 cells exposed to hydrogen peroxide, alkylating agents, and the lipid oxidation-derived electrophile 4-hydroxynonenal, which is an ubiquitous product of lipid oxidation associated with oxidative stress. Confocal immunofluorescence microscopy indicated that in unstressed cells sumo-1 targeted nuclear proteins, whereas sumo-2/3 targeted proteins in both nuclei and cytoplasm. Western blot analyses revealed changes in sumo-1 and sumo-2/3 targeting patterns with stress. We used immunoaffinity chromatography to harvest sumo-associated proteins from HA-sumo-1- and HA-sumo-3-expressing HEK293 cells both before and after treatment with 4-hydroxynonenal. Multidimensional liquid chromatography-tandem mass spectrometry analyses identified 54 HA-sumo-1-associated proteins and 38 HA-sumo-3-associated proteins. Major protein targets included RNA binding and processing proteins, transcription factors, metabolic enzymes, and cytoskeletal regulators. Treatment with 4-hydroxynonenal caused a near-complete redistribution of sumo-1 and sumo-3 to different protein targets, which included chaperones, antioxidant, and DNA damage signaling proteins. A 10-15% overlap of sumo-1 and sumo-3 targets before and after stress suggests that sumo proteins target distinct protein groups. The results suggest that reactive electrophiles not only directly modify proteins but also lead to indirect changes in endogenous protein modifications that regulate protein functions.
Treatment of Ankylosing Spondylitis by Inhibition of Tumor Necrosis Factor α (2002)

Treatment with etanercept for four months resulted in rapid, significant, and sustained improvement in patients with ankylosing spondylitis.
Important Role for the Transmembrane Domain of Severe Acute Respiratory Syndrome Coronavirus Spike Protein during Entry (2006)

The spike protein (S) of severe acute respiratory syndrome coronavirus (SARS-CoV) is responsible for receptor binding and membrane fusion. It contains a highly conserved transmembrane domain that consists of three parts: an N-terminal tryptophan-rich domain, a central domain, and a cysteine-rich C-terminal domain. The cytoplasmic tail of S has previously been shown to be required for assembly. Here, the roles of the transmembrane and cytoplasmic domains of S in the infectivity and membrane fusion activity of SARS-CoV have been studied. SARS-CoV S-pseudotyped retrovirus (SARSpp) was used to measure S-mediated infectivity. In addition, the cell-cell fusion activity of S was monitored by a Renilla luciferase-based cell-cell fusion assay. S(VSV-Cyt), an S chimera with a cytoplasmic tail derived from vesicular stomatitis virus G protein (VSV-G), and S(MHV-TMDCyt), an S chimera with the cytoplasmic and transmembrane domains of mouse hepatitis virus, displayed wild-type-like activity in both assays. S(VSV-TMDCyt), a chimera with the cytoplasmic and transmembrane domains of VSV-G, was impaired in the SARSpp and cell-cell fusion assays, showing 3 to 25% activity compared to the wild type, depending on the assay and the cells used. Examination of the oligomeric state of the chimeric S proteins in SARSpp revealed that S(VSV-TMDCyt) trimers were less stable than wild-type S trimers, possibly explaining the lowered fusogenicity and infectivity.
Precise determination of starting time of epileptic seizures using subdural EEG and wavelet transforms (2002)

Biorthogonal wavelet transforms are applied to multichannel subdural electroencephalographic data to determine the time of epileptic seizure onset. A soft-thresholding technique is utilized to separate the ictal activity using a set of threshold values computed from manually selected training segments. The time points of seizure onset are detected by a new data integration procedure.
Service specification description using extended message sequence charts between network and users (2002)

NTT's advanced intelligent network (IN) provides telecommunication services by using service logic programs (SLPs). These programs are executed on service-independent platforms in service control points (SCPs). The source codes of the SLPs are automatically generated in a service creation environment (SCE) by describing the service specifications in graphical form. We propose using extended message sequence charts (E-MSCs) for describing the service specifications of the advanced IN. The E-MSCs are used to represent the service procedures between the network and users. We previously proposed using the E-MSCs for describing general service specifications. By adding new descriptive elements, they can also be used to describe the service specifications of the commercial advanced IN. Three types of programs executed to provide telecommunication services are also described.
SYNTHESIS OF 4-(Ν-ΑLΚΥL/ΑRΥL-Ν-ΝΙΤROSOΑΜΙDΟ)-2,3-DΙΗΥDRΟ-1,4-ΒΕΝΖΟΤΗΙΑΖΙΝΕS (1996)

Synthesis of title compounds in which heterocyclic nitrogen of 1,4-benzothiazines involves in constituting urea linkage is reported first time. Synthesis involves the reactions of 1,4-benzothiazines with alkyl/aryl isocyanates and subsequent nitrosation.
Fiber-coupling technique with micro step-mirrors for high-power diode laser bars (1997)

A technique for coupling the output of a high-power diode laser bar into one multimode fiber with high efficiency, easy alignment requirements and low manufacturing costs is demonstrated using a single fiber with 400 μm core diameter. This technique comprises two micro step-mirrors for beam shaping. The overall efficiency from diode-laser to fiber is 71% with 20 W cw laser power through the fiber.
Kirby-Bauer Disk Diffusion Susceptibility Test Protocol (2009)

Protocol for using the Kirby-Bauer disk diffusion susceptibility test in the microbiology lab.