gebhart/patrepeval huggingface dataset:
Mutations in the Yeast LCB1 and LCB2Genes, Including Those Corresponding to the Hereditary Sensory Neuropathy Type I Mutations, Dominantly Inactivate Serine Palmitoyltransferase (2002)

It was recently demonstrated that mutations in the human SPTLC1 gene, encoding the Lcb1p subunit of serine palmitoyltransferase (SPT), cause hereditary sensory neuropathy type I . As a member of the subfamily of pyridoxal 5'-phosphate enzymes known as the alpha-oxoamine synthases, serine palmitoyltransferase catalyzes the committed step of sphingolipid synthesis. The residues that are mutated to cause hereditary sensory neuropathy type I reside in a highly conserved region of Lcb1p that is predicted to be a catalytic domain of Lcb1p on the basis of alignments with other members of the alpha-oxoamine synthase family. We found that the corresponding mutations in the LCB1 gene of Saccharomyces cerevisiae reduce serine palmitoyltransferase activity. These mutations are dominant and decrease serine palmitoyltransferase activity by 50% when the wild-type and mutant LCB1 alleles are coexpressed. We also show that serine palmitoyltransferase is an Lcb1p small middle dotLcb2p heterodimer and that the mutated Lcb1p proteins retain their ability to interact with Lcb2p. Modeling studies suggest that serine palmitoyltransferase is likely to have a single active site that lies at the Lcb1p small middle dotLcb2p interface and that the mutations in Lcb1p reside near the lysine in Lcb2p that is expected to form the Schiff's base with the pyridoxal 5'-phosphate cofactor. Furthermore, mutations in this lysine and in a histidine residue that is also predicted to be important for pyridoxal 5'-phosphate binding to Lcb2p also dominantly inactivate SPT similar to the hereditary sensory neuropathy type 1-like mutations in Lcb1p.
Standardization of the Filovirus Plaque Assay for Use in Preclinical Studies (2012)

The filovirus plaque assay serves as the assay of choice to measure infectious virus in a cell culture, blood, or homogenized tissue sample. It has been in use for more than 30 years and is the generally accepted assay used to titrate virus in samples from animals treated with a potential antiviral therapeutic or vaccine. As these animal studies are required for the development of vaccines and therapeutics under the FDA Animal Rule, it is essential to have a standardized assay to compare their efficacies against the various filoviruses. Here, we present an evaluation of the conditions under which the filovirus plaque assay performs best for the Ebola virus Kikwit variant and the Angola variant of Marburg virus. The indicator cell type and source, inoculum volumes, length of incubation and general features of filovirus biology as visualized in the assay are addressed in terms of the impact on the sample viral titer calculations. These optimization studies have resulted in a plaque assay protocol which can be used for preclinical studies, and as a standardized protocol for use across institutions, to aid in data comparison. This protocol will be validated for use in GLP studies supporting advanced development of filovirus therapeutics and vaccines.
Neuraminidase Sequence Analysis and Susceptibilities of Influenza Virus Clinical Isolates to Zanamivir and Oseltamivir (2003)

The influenza virus neuraminidase (NA) inhibitors zanamivir and oseltamivir were introduced into clinical practice in various parts of the world between 1999 and 2002. In order to monitor the potential development of resistance, the Neuraminidase Inhibitor Susceptibility Network was established to coordinate testing of clinical isolates collected through the World Health Organization influenza surveillance network from different regions of the world (M. Zambon and F. G. Hayden, Antivir. Res. 49:147-156, 2001). The present study establishes the baseline susceptibilities prior to and shortly after the introduction of the NA inhibitors. Over 1000 clinical influenza isolates recovered from 1996 to 1999 were tested. Susceptibilities were determined by enzyme inhibition assays with chemiluminescent or fluorescent substrates with known NA inhibitor-resistant viruses as controls. The 50% inhibitory concentrations (IC(50)s) depended upon the assay method, the drug tested, and the influenza virus subtype. By both assays, the mean zanamivir IC(50)s were 0.76, 1.82, and 2.28 nM for the subtype H1N1 (N1), H3N2 (N2), and B NAs, respectively, and the oseltamivir IC(50)s were 1.2, 0.5, and 8.8 nM for the N1, N2, and B NAs, respectively. The drug susceptibilities of known zanamivir- and oseltamivir-resistant viruses with the NA mutations E119V, R292K, H274Y, and R152K fell well outside the 95% confidence limits of the IC(50)s for all natural isolates. Sequence analysis of the NAs of viruses for which the IC(50)s were above the 95% confidence limits and several control isolates for which the IC(50)s were in the normal range revealed variations in some previously conserved residues, including D151, A203, T225, and E375 (N2 numbering). Known resistance mutations are both influenza virus subtype and drug specific, but there was no evidence of naturally occurring resistance to either drug in any of the isolates.
In Vitro and in Vivo Evaluation of Native Glucagon and Glucagon Analog (MAR-D28) during Aging: Lack of Cytotoxicity and Preservation of Hyperglycemic Effect (2010)

Under certain conditions, aqueous solutions of glucagon and MAR-D28 are stable for at least 5 days and are thus very likely to be safe in mammals. Glycine buffer at a pH of 10 appears to be optimal for avoiding cytotoxicity and amyloid fibril formation.
Codes on graphs: normal realizations (2001)

A generalized state realization of the Wiberg (1996) type is called normal if symbol variables have degree 1 and state variables have degree 2. A natural graphical model of such a realization has leaf edges representing symbols, ordinary edges representing states, and vertices representing local constraints. Such a graph can be decoded by any version of the sum-product algorithm. Any state realization of a code can be put into normal form without essential change in the corresponding graph or in its decoding complexity. Group or linear codes are generated by group or linear state realizations. On a cycle-free graph, there exists a well-defined minimal canonical realization, and the sum-product algorithm is exact. However, the cut-set bound shows that graphs with cycles may have a superior performance-complexity tradeoff, although the sum-product algorithm is then inexact and iterative, and minimal realizations are not well-defined. Efficient cyclic and cycle-free realizations of Reed-Muller (RM) codes are given as examples. The dual of a normal group realization, appropriately defined, generates the dual group code. The dual realization has the same graph topology as the primal realization, replaces symbol and state variables by their character groups, and replaces primal local constraints by their duals. This fundamental result has many applications, including to dual state spaces, dual minimal trellises, duals to Tanner (1981) graphs, dual input/output (I/O) systems, and dual kernel and image representations. Finally a group code may be decoded using the dual graph, with appropriate Fourier transforms of the inputs and outputs; this can simplify decoding of high-rate codes.
Sequence-specific targeting and covalent modification of human genomic DNA (1997)

We compare two techniques which enable selective, nucleotide-specific covalent modification of human genomic DNA, as assayed by quantitative ligation- mediated PCR. In the first, a purine motif triplex-forming oligonucleotide with a terminally appended chlorambucil was shown to label a target guanine residue adjacent to its binding site in 80% efficiency at 0.5 microM. Efficiency was higher in the presence of the triplex-stabilizing intercalator coralyne. In the second method, an oligonucleotide targeting a site containing all four bases and bearing chlorambucil on an interior base was shown to efficiently react with a specific nucleotide in the target sequence. The targeted sequence in these cases was in the DQbeta1*0302 allele of the MHC II locus.
Water‐Soluble Polymers (2000)

Abstract Water‐soluble polymers find application in a wide variety of areas that include polymers as food sources, plasma substitute, and as diluents in medical prescriptions. Other areas of importance for water‐soluble polymers include detergents, cosmetics, sewage treatment, stabilizing agents in the production of commodity plastics, rheology modifiers in the various processes for petroleum textile, paper, and latex coatings production. This article discusses the general features of polymers that influence their water solubility and solution properties. Carbohydrate polymers, cellulose, synthetics, cationic polymers, inorganic polymers, new commercial polymers, and hydrophobe‐modification polymers are discussed.
Analysis of the SOS inducing signal in Bacillus subtilis using Escherichia coli LexA as a probe (1994)

We analyzed the Bacillus subtilis SOS response using Escherichia coli LexA protein as a probe to measure the kinetics of SOS activation and DNA repair in wild-type and DNA repair-deficient strains. By examining the effects of DNA-damaging agents that produce the SOS inducing signal in E. coli by three distinct pathways, we obtained evidence that the nature of the SOS inducing signal has been conserved in B. subtilis. In particular, we used the B. subtilis DNA polymerase III inhibitor, 6-(p-hydroxyphenylazo)-uracil, to show that DNA replication is required to generate the SOS inducing signal following UV irradiation. We also present evidence that single-stranded gaps, generated by excision repair, serve as part of the UV inducing signal. By assaying the SOS response in B. subtilis dinA, dinB, and dinC mutants, we identified distinct deficiencies in SOS activation and DNA repair that suggest roles for the corresponding gene products in the SOS response.
Antibody Conjugates for Cell Biology (2000)

Antibody conjugates are extremely useful reagents for probing many biologically and chemically important molecules in vitro or in vivo. This unit presents some basic protocols for conjugating antibodies with fluorescent dyes, with biotin, and with enzymes. These protocols have been selected because they are relatively easy to perform and have high rates of success. The basic approach for conjugating antibodies is to derivatize amino groups on the antibody with the dye or biotin derivative of choice. Conjugation at amine sites is simple to perform, and, with a fluorescent dye, it generally yields brightly fluorescent conjugates. The conjugates retain high levels of biological activity, notwithstanding the fact that the labels react with random amines on the antibody molecule, and they may even react near or at the antigen-binding site. Labeling of the amines is the most widely used commercial method to tag antibodies. In this unit, suggestions are presented for variations on these basic protocols that are useful when quantities of available antibody are limited. Methods for estimating antibody concentration are also included.
Profile of phosphoprotein labelling in organotypic slice cultures of rat hippocampus (2001)

In recent years organotypic slice cultures of hippocampal tissue of rats have been widely used to study factors involved in neuronal death. Here we used 2D electrophoresis to study the phosphoprotein profile in such cultures and the effect of oxygen/glucose deprivation on this profile. Cultures were prepared from 7-day-old rats. After 14 days in culture the phosphorylation profile in the cultures, as shown by phospho-protein markers undergoing developmental change, closely resembled the profile of fresh tissue from 23-day-old rats. The results suggest that this model could be a good method to observe the development of the tissue and its response to an ischaemic lesion
Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components (2004)

We present an analysis for polarization-sensitive optical coherence tomography that facilitates the unrestricted use of fiber and fiber-optic components throughout an interferometer and yields sample birefringence, diattenuation, and relative optic axis orientation. We use a novel Jones matrix approach that compares the polarization states of light reflected from the sample surface with those reflected from within a biological sample for pairs of depth scans. The incident polarization alternated between two states that are perpendicular in a Poincaré sphere representation to ensure proper detection of tissue birefringence regardless of optical fiber contributions. The method was validated by comparing the calculated diattenuation of a polarizing sheet, chicken tendon, and muscle with that obtained by independent measurement. The relative importance of diattenuation versus birefringence to angular displacement of Stokes vectors on a Poincaré sphere was quantified.
Characterization of a distinct binding site for the prokaryotic chaperone, GroEL, on a human granulocyte ribonuclease. (1993)

Although ribonucleases fold into correct tertiary conformation in vitro guided solely by information contained in the primary amino acid sequence (Sela, M., White, F. H., and Anfinsen, C. B. (1957) Science 124, 691-693), it is not clear whether folding of these proteins proceeds unassisted in a complex intracellular environment. We describe here the specific and high affinity binding of groEL, the prokaryotic homolog of the heat shock protein 60 family of molecular chaperones, to recombinant eosinophil cationic protein and eosinophil-derived neurotoxin, two members of the human ribonuclease gene family. We have determined that groEL binds to a unique peptide sequence near the amino terminus of nascent eosinophil cationic protein that includes the first of eight cysteine residues. This binding site functions independently and can confer groEL binding activity on an unrelated carrier protein. GroEL dissociates from the binding site upon addition of ATP and Mg2+; no other cations or cofactors are necessary. These findings suggest the possibility that interaction with a groEL-like molecular chaperone may be a requirement for correct folding and/or translocation of eukaryotic ribonucleases in vivo.
A New Cytotoxic Epothilone from Modified Polyketide Synthases Heterologously Expressed in Myxococcus xanthus (2002)

A new epothilone, 10,11-didehydroepothilone D (5), was isolated from a strain of the heterologous host Myxococcus xanthus genetically engineered to produce epothilone D (4). The structure of 5 was determined from NMR and MS data. The epothilone polyketide synthase was further modified in a recombinant M. xanthus strain to produce 5 as the major epothilone-related metabolite. The cytotoxicity of 5 against a panel of tumor cell lines, including several with multidrug resistance, and its effect on tubulin polymerization were comparable to epothilone D (4).
The central role of dendritic cells and interferon-α in SLE (2003)

The disease model that the authors propose places interferon-alpha at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-alpha and/or interferon-alpha-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.
Resituating the Community College in a Global Context (2013)

Abstract From locally focused institutions intent on access and affordability to higher education, workforce preparation, and community engagement, the contemporary community college is poised as a global partner for the democratization and development of a global workforce.
Cloning and expression of a novel cyclic GMP-dependent protein kinase from mouse brain (1993)

Synthetic oligonucleotides were used to amplify mouse brain cDNA sequences homologous to conserved regions of known cGMP-dependent protein kinases, and two classes of products were identified. The first class (CGKI) of amplification products contained approximately 1.0 kilobase (kb) of DNA sequence between the oligonucleotide primers, and this sequence showed a high degree of homology (90% identity) with the known bovine and human type I cDNA sequences for cGMP-dependent protein kinase. The second class (CGKII) of amplification products contained approximately 1.1 kb of DNA sequence between the oligonucleotide primers, and this sequence showed a much lower homology (65% identity) with the bovine and human type I cDNA sequences. Northern blot analysis showed that CGKI transcripts of 8.5 kb were abundant in brain and lung, whereas a 7-kb transcript could be detected in testis. CGKII transcripts of 6 kb were also abundant in brain and lung but could be detected at lower levels in kidney. The CGKII amplification product was used to screen a mouse brain cDNA library, and four overlapping cDNA clones were isolated which comprised the entire CGKII coding region. The predicted CGKII protein consists of 761 amino acids and has a molecular mass of 87 kDa. The CGKII protein shows highest homology to the catalytic (66% amino acid identity) and regulatory domains (45% identity) of bovine and human CGKI. Little homology is observed at the amino terminus or in the region linking the regulatory and catalytic domains. An expression vector for mouse CGKII was constructed and transfected into COS-1 cells where it directed the expression of a protein kinase which was activated by cGMP with an apparent K alpha of 300 nM cGMP.
Expensive Multiobjective Optimization by MOEA/D With Gaussian Process Model (2009)

In some expensive multiobjective optimization problems (MOPs), several function evaluations can be carried out in a batch way. Therefore, it is very desirable to develop methods which can generate multipler test points simultaneously. This paper proposes such a method, called MOEA/D-EGO, for dealing with expensive multiobjective optimization. MOEA/D-EGO decomposes an MOP in question into a number of single-objective optimization subproblems. A predictive model is built for each subproblem based on the points evaluated so far. Effort has been made to reduce the overhead for modeling and to improve the prediction quality. At each generation, MOEA/D is used for maximizing the expected improvement metric values of all the subproblems, and then several test points are selected for evaluation. Extensive experimental studies have been carried out to investigate the ability of the proposed algorithm.
Design of sample-and-hold amplifiers for high-speed low-voltage A/D converters (2002)

Multi-step analog-to-digital converters typically employ a sample-and-hold amplifier at the front end that must achieve high speed and high linearity with low power dissipation. Furthermore, sampling circuits can be used to alleviate the timing and bandwidth limitations of one-step converters such as flash and interpolative architectures. This paper describes design techniques for sample-and-hold circuits utilized in high-speed low-voltage data converters, Following a review of the role of sampling in various converter architectures, two broad categories of sampling techniques are introduced and properties of basic analog switches are summarized. Next, conventional sampling architectures are discussed, design methods for CMOS, bipolar, and BiCMOS implementations are studied, and several examples embodying these methods are presented. Finally, characterization of high-speed sampling circuits is described.
Novel synthesis of pyrimido[4,5-b]quinoline-2(3H),4(10H)-diones (5-deazaflavins) (1978)

K. Mori, K. Shinozuka, Y. Sakuma and F. Yoneda, J. Chem. Soc., Chem. Commun., 1978, 764 DOI: 10.1039/C39780000764
CD154 Is Essential for Protective Immunity in Experimental Salmonella Infection: Evidence for a Dual Role in Innate and Adaptive Immune Responses (2006)

CD40-CD154 interactions are of central importance in the induction of humoral and cellular immune responses. In the present study, CD154-deficient (CD154-/-) mice were used to assess the role of CD40-CD154 interactions in regulating the immune response to a systemic Salmonella infection. Compared with C57BL/6 (CD154+/+) controls, CD154-/- mice were hypersusceptible to infection by an attenuated strain of Salmonella enterica serovar Typhimurium (S. typhimurium), as evidenced by decreased survival rate and mean time to death, which correlated with increased bacterial burden and persistence in target organs. CD154-/- mice exhibited a defect both in the production of IL-12, IFN-gamma, and NO during the acute phase of the disease and in the generation of Salmonella-specific Ab responses and Ig isotype switching. Furthermore, when CD154-/- animals were administered a sublethal dose of attenuated S. typhimurium and subsequently challenged with a virulent homologous strain, all mice succumbed to an overwhelming infection. Similar treatment of CD154+/+ mice consistently resulted in > or =90% protection. The lack of protective immunity in CD154-/- mice correlated with a decreased T cell recall response to Salmonella Ags. Significant protection against virulent challenge was conferred to presensitized CD154-/- mice by transfer of serum or T cells from immunized CD154+/+ mice. For best protection, however, a combination of immune serum and T cells was required. We conclude that intercellular communications via the CD40-CD154 pathway play a critical role in the induction of type 1 cytokine responses, memory T cell generation, Ab formation, and protection against primary as well as secondary Salmonella infections.
Beneficial Effects of Insulin Versus Sulphonylurea on Insulin Secretion and Metabolic Control in Recently Diagnosed Type 2 Diabetic Patients (2003)

Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.
Gastrodin Rescues Autistic-Like Phenotypes in Valproic Acid-Induced Animal Model (2018)

Autism spectrum disorder (ASD) is an immensely challenging developmental disorder characterized by impaired social interaction, restricted/repetitive behavior, and anxiety. GABAergic dysfunction has been postulated to underlie these autistic symptoms. Gastrodin is widely used clinically in the treatment of neurological disorders and showed to modulate GABAergic signaling in the animal brain. The present study aimed to determine whether treatment with gastrodin can rescue valproic acid (VPA) induced autistic-like phenotypes, and to determine its possible mechanism of action. Our results showed that administration of gastrodin effectively alleviated the autistic-associated behavioral abnormalities as reflected by an increase in social interaction and decrement in repetitive/stereotyped behavior and anxiety in mice as compared to those in untreated animals. Remarkably, the amelioration in autistic-like phenotypes was accompanied by the restoration of inhibitory synaptic transmission, α5 GABA<sub>A</sub> receptor, and type 1 GABA transporter (GAT1) expression in the basolateral amygdala (BLA) of VPA-treated mice. These findings indicate that gastrodin may alleviate the autistic symptoms caused by VPA through regulating GABAergic synaptic transmission, suggesting that gastrodin may be a potential therapeutic target in autism.
Electrostatic discharge (ESD) protection of giant magneto-resistive (GMR) recording heads with a silicon germanium technology (2004)

Experimental studies on the ESD protection were completed on advanced magnetic recording giant magneto-resistive heads using a BiCMOS silicon germanium technology for the first time. SiGe-based active and passive elements, such as isolated MOSFETs, varactors and Schottky diodes were used to evaluate the influence of turn-on voltage on the protection levels.