gebhart/patrepeval huggingface dataset:
Structure-activity relationships of N2-substituted guanines as inhibitors of HSV1 and HSV2 thymidine kinases (1990)

A series of N2-phenylguanines was synthesized and tested for inhibition of the thymidine kinases encoded by Herpes simplex viruses type 1 and type 2. Compounds with hydrophobic, electron-attracting groups in the meta position of the phenyl ring such as m-trifluoromethyl (m-CF3PG, IC50 = 0.1 microM) were the most potent inhibitors of both enzymes. Many derivatives were significantly more potent against the type 2 thymidine kinase, and can effectively discriminate between the two enzymes. Among other N2-substituted guanines, alkyl and benzyl derivatives were moderately potent inhibitors, and the type 2 enzyme was again more sensitive than the type 1 enzyme. None of the compounds inhibited the thymidine kinase isolated from the host HeLa cell line, suggesting that members of this class of compounds may be useful nonsubstrate, antiviral compounds for latent herpesvirus infections.
Multimode interference bistable laser diode (2003)

We propose a novel bistable laser diode (BLD) with active multimode interference (MMI) cavity. Bistable switching can be realized between two cross-coupled modes by means of gain saturation. Static characteristics of the multimode interference (MMI)-BLD are analyzed using a finite-difference beam propagation method. The photon-carrier interactions are calculated using the carrier-rate equation. This model gives accurate distributions of photon and carrier densities, optical gain, and refractive index inside the cavity. We predict that the MMI-BLD shows bistable switching between the two cross-coupled modes by light injection, therefore allowing it to be used as all-optical flip-flop or optical memory.
A novel frizzled gene identified in human esophageal carcinoma mediates APC/β-catenin signals (1998)

A novel member of the human frizzled (Fz) gene family was cloned and found to be specifically expressed in 3 of 13 well differentiated (23%), 13 of 20 moderately differentiated (62%), and 12 of 14 poorly differentiated (86%) squamous cell esophageal carcinomas compared with the adjacent uninvolved normal mucosa. The FzE3 cDNA encodes a protein of 574 amino acids and shares high sequence homology with the human FzD2 gene particularly in the putative ligand binding region of the cysteine-rich extracellular domain. Functional analysis revealed that transfection and expression of the FzE3 cDNA in esophageal carcinoma cells stimulates complex formation between adenomatous polyposis coli (APC) and beta-catenin followed by nuclear translocation of beta-catenin. Furthermore, cotransfection of a mutant construct encoding a FzE3 protein with a C-terminal truncation completely inhibited the interaction of APC with beta-catenin in cells. Finally, coexpression of FzE3 with Lef-1 transcription factor enhanced beta-catenin translocation to the nucleus. These observations suggest that FzE3 gene expression may down-regulate APC function and enhance beta-catenin mediated signals in poorly differentiated human esophageal carcinomas.
The Changing Culture of the Microbiology Laboratory (2013)

The development and implementation of novel diagnostic techniques has had a profound effect on microbiology laboratory services in recent decades. Traditional microscopy, culture and biochemical testing techniques have been the mainstay for identification and anti-microbial susceptibility testing of microorganisms for generations (1,2). While these tests remain the core basis and standard practice in most laboratories, new techniques, such as nucleic acid-based assays and mass spectrometry, are increasingly being used. In some cases, these are enhancing existing diagnostic algorithms and, in others, they are replacing traditional testing approaches. Although these new techniques are powerful and offer many potential advantages over traditional methods, they have a number of limitations. In the present note, we briefly review new and evolving testing modalities in the microbiology laboratory. It is important to note that we did not intend to provide an in-depth technical appraisal of testing modalities. Rather, our objective was to highlight a number of new testing modalities in the context of traditional testing for bedside clinicians.
CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene (1993)

To detect novel molecules involved in immune functions, a subtracted cDNA library between closely related murine lymphoid cells was prepared using improved technology. Differential screening of this library yielded several clones with a very restricted tissue specificity, including one that we named CTLA-8. CTLA-8 transcripts could be detected only in T cell hybridoma clones related to the one used to prepare the library. Southern blots showed that the CTLA-8 gene was single copy in mice, rats, and humans. By radioactive in situ hybridization, the CTLA-8 gene was mapped at a single site on mouse chromosome 1A and human chromosome 2q31, in a known interspecific syntenic region. The CTLA-8 cDNA sequence indicated the presence, in the 3'-untranslated region of the mRNA, of AU-rich repeats previously found in the mRNA of various cytokines, growth factors, and oncogenes. The CTLA-8 cDNA contained an open reading frame encoding a putative protein of 150 amino acids. This protein was 57% homologous to the putative protein encoded by the ORF13 gene of herpesvirus Saimiri, a T lymphotropic virus. These findings are discussed in the context of other genes of this herpesvirus homologous to known immunologically active molecules. More generally, CTLA-8 may belong to the growing set of virus-captured functionally important cellular genes related to the immune system or to cell death and cell survival.
Group-delay measurement on laser mirrors by spectrally resolved white-light interferometry (1995)

The frequency-dependent group delay of dielectric mirrors was measured by spectrally resolved white-light interferometry. Chirped mirrors and thin-film Gires-Tournois interferometers designed for dispersion control in a femtosecond Ti:sapphire laser oscillator-amplifier system were tested with a group-delay resolution of +/-0.2 fs and a spectral resolution of ~1 nm over the spectral range of 670-870 nm.
Influence of the polarization of the object and reference waves on the hologram quality (1979)

An analysis is made of the influence of the object and reference wave polarizations on the hologram quality. It is proposed to use a circularly polarized reference wave to record radiation with various polarizations. A relationship between the diffraction efficiency of a hologram and the polarization of the object and reference waves is established.
Aminoglycoside-induced mutation suppression (stop codon readthrough) as a therapeutic strategy for Duchenne muscular dystrophy (2010)

Duchenne muscular dystrophy (DMD) is the most common, lethal, X-linked genetic disease, affecting 1 in 3500 newborn males. It is caused by mutations in the DMD gene. Owing to the large size of the gene, the mutation rate in both germline and somatic cells is very high. Nearly 13-15% of DMD cases are caused by nonsense mutations leading to premature termination codons in the reading frame that results in truncated dystrophin protein. Currently there is no cure for DMD. The only available treatment is the use of glucocorticoids that have modest beneficial effects accompanied by significant side effects. Different therapeutic strategies have been developed ranging from gene therapy to exon skipping and nonsense mutation suppression to produce the full-length protein. These strategies have shown promise in the mdx mouse model of muscular dystrophy where they have been reported to ameliorate the dystrophic phenotype and correct the physiological defects in the membrane. Each of these molecular approaches are being investigated in clinical trials. Here we review nonsense mutation suppression by aminoglycosides as a therapeutic strategy to treat DMD with special emphasis on gentamicin-induced readthrough of disease-causing premature termination codons.
Development of Integrated Process Simulation System Model for Spent Fuel Treatment Facility (SFTF) Design: Quarterly Progress Report January 1-March 31, 2005 (2005)

The Advanced Fuel Cycle Initiative (AFCI) and Transmutation Research Program-University Participation Program (TRP-UPP) supported by Department of Energy of the United States have been developing many important technologies for the transmutation of nuclear waste to address long-term disposal issues. While successfully embedding AMUSE module into a dedicated System Engineering Model (TRPSEMPro), developed by the Nevada Center for Advanced Computational Methods (NCACM) at the University of Nevada-Las Vegas collaborating with Argonne National Laboratory (ANL), ANL is interested in further simulating the Light Water Reactor (LWR) Spent Fuel Treatment Facility (SFTF) combining commercial process simulation and analysis packages and core calculation of the AMUSE that derived for using with the UREX+ process. The designed SFTF will receive, temporarily store, and prepare spent nuclear fuel for leaching. The major objectives of this research proposal are to develop a framework for simulating the Spent Fuel Treatment Facility (SFTF) process using AMUSE code, commercial process package such as ASPEN-PLUS, HYSYS and PRO/II and system engineering model such as TRPSEMPro’s flexible parameter optimization modules, to develop a middleware package that can communicate between the AMUSE code and any selected commercial packages, to extend the existing system engineering model for optimization process that includes process simulation results, and to include a scenario-based database system that efficiently reports required information as chart output using web-based programming, and Microsoft Visual Basic (MS VB).
Engineered Biosynthesis of Novel Polyketides: actVII and actIV Genes Encode Aromatase and Cyclase Enzymes, Respectively (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEngineered Biosynthesis of Novel Polyketides: actVII and actIV Genes Encode Aromatase and Cyclase Enzymes, RespectivelyRobert McDaniel, Susanne Ebert-Khosla, David A. Hopwood, and Chaitan KhoslaCite this: J. Am. Chem. Soc. 1994, 116, 24, 10855–10859Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November 1994https://pubs.acs.org/doi/10.1021/ja00103a001https://doi.org/10.1021/ja00103a001research-articleACS PublicationsRequest reuse permissionsArticle Views500Altmetric-Citations88LEARN 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-Alertsclose Get e-Alerts
Ultrasensitive electrochemical detection of prostate-specific antigen (PSA) using gold-coated magnetic nanoparticles as ‘dispersible electrodes’ (2012)

Herein, we demonstrate the use of modified gold-coated magnetic nanoparticles as 'dispersible electrodes' which act as selective capture vehicles for electrochemical detection of prostate-specific antigen (PSA). A key advantage of this system is the ability to quantify non-electrochemical active analytes such as proteins with unprecedented detection limits and fast response times.
Growth, Survival and Migration: The Trk to Cancer (2006)

Trk signaling is of widespread importance during development as it regulates the differentiation, survival and migration of multiple cell types. Similar fanctions for Trks can be found in a wide variety of cancers. These activities not only determine the biology of these cancers but also offer a potentially unique target for the control of cancer cell growth and motility through the inhibition of the Trk kinase.
The Greatest of a Finite Set of Random Variables (1961)

The variables ξ 1 , …, ξ n have a joint normal distribution. We are concerned with the calculation or approximation of max(ξ 1 , …, ξ n ). Current analyses and tables handle the case in which the ξ ı are independently distributed with common expected values and common variances. This paper presents formulas and tables for the most general case with n = 2. When n &gt; 2, the problem becomes cumbersome. This paper presents formulas and tables that permit approximations to the moments in case n &gt; 2. The moments are approximated by iteration of a three-parameter computation or, alternatively, through successive use of a three-parameter table, which is given. Recent applications of the theory are described.
Routine Preparation of Thiol Oligonucleotides: Application to the Synthesis of Oligonucleotide-Peptide Hybrids (1994)

Oligonucleotide-peptide hybrids have potential for use as antisense inhibitors of gene expression, with the peptide helping to increase the intracellular concentration of the active oligonucleotide. The preparation of such hybrids can be achieved by the coupling of thiol-derivatized oligonucleotides with maleimido-peptides. We have developed reliable methods for preparing 5'-thiol oligonucleotides in good yields using phosphoramidite chemistry and coupling 6-(tritylthio)hexyl phosphoramidite as the 5'-terminal residue. The use of highly pure thiol phosphoramidite as well as a manual iodine treatment after this coupling were found to be important. Oligonucleotide-peptide hybrids were prepared in high yield (85%) by reacting freshly purified 5'-thiol oligonucleotides with peptides derivatized at their N-terminus with a maleimido functionality.
Unraveling the mysteries of serum albuminâ€”more than just a serum protein (2014)

Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. The development of albumin drug carriers is gaining increasing importance in the targeted delivery of cancer therapy, particularly as a result of the market approval of the paclitaxel-loaded albumin nanoparticle, Abraxane®. Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake. Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body. Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.
Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia (2006)

In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.
A Facile Route towards the Preparation of Ultra-Long-Chain Amidosulfobetaine Surfactants (2009)

A series of novel, ultra-long-chain amidosulfobetaine surfactants were prepared by amidation of ultra-long-chain fatty acids directly with N,N-dimethyl-1,3-propanediamine in the absence of solvents, followed by quaternization of the intermediates with 1,3-propanesultone in ethyl acetate.
Palladium-Catalyzed Coupling of Oxazol-2-yl- and 2-Oxazolin-2-yltrimethylstannanes with Aromatic Halides. A New Entry to 2-Aryl and 2-Heteroaryl Oxazoles and Oxazolines (1987)

4-Methyloxazole and 4,4-dimethyl-2-oxazoline were treated with n-butyllithium and trimethyltin chloride to give the corresponding 2-trimethylstannyl derivatives which in the presence of tetrakis(triphenylphosphine)palladium(0) as a catalyst undergo cross-coupling reactions with various aryl and heteroaryl halides to give 2-aryl and 2-heteroaryl oxazoles and oxazolines in high yields.
Altered cholesterol metabolism in a hypercholesterolemia -resistant rabbit colony (1991)

A colony of rabbits has been developed at the University of Texas Medical School at Houston that is resistant to dietary-induced hypercholesterolemia. The liver of resistant rabbits had higher levels of ($\sp{125}$I) $\beta$-VLDL binding and 3-hydroxy-3-methylglutaryl (HMGCoA) reductase activity, but lower acyl coenzyme A:cholesterol acyltransferase (ACAT) activity than normal rabbits. Direct quantitation of intracellular cholesterol content of the liver revealed that the resistant rabbits had $<$10% of the intracellular free cholesterol present in normal rabbits. Fibroblasts isolated from normal and resistant rabbits exhibited differences in ($\sp{125}$I) LDL binding, HMGCoA reductase activity and ACAT activity that were similar to those found in the liver. No structural differences were found in the LDL receptor of normal and resistant fibroblasts that would account for the increased binding capacity of the resistant cells. The regulation of LDL receptor levels by exogenous oxygenated sterols was similar in normal and resistant fibroblasts. The regulation of LDL receptor binding capacity by LDL was attenuated in the resistant compared to normal fibroblasts, suggesting that the resistant fibroblasts have an alternate pathway for processing lipoprotein-derived cholesterol. Sterol-balance studies revealed that the cholesterol-fed resistant rabbits increased lithocholic acid excretion compared to the basal state, and had higher levels of deoxycholic acid excretion than cholesterol-fed normal rabbits. In addition, the specific activity and mRNA levels of cholesterol 7$\alpha$-hydroxylase (C7$\alpha$H) were higher in resistant rabbits than normal rabbits, suggesting that the increased bile acid excretion was due to an increase in bile acid synthesis. Increased clearance of cholesterol relieves the negative feedback inhibition cholesterol exerts on expression of the LDL receptor. The number of cell surface LDL receptors is then increased in resistant rabbits and allows rapid clearance of lipoproteins from the plasma compartment, thereby reducing plasma cholesterol levels. The low intracellular cholesterol level also relieves the negative feedback inhibition cholesterol exerts on HMGCoA reductase. Increased synthesis of cholesterol from acetate provides cells with cholesterol for bile acid synthesis and/or homeostasis. The activity of ACAT is then decreased due to the flux of cholesterol through the bile acid synthetic pathways.
A Bivalent Ligand (KDAN-18) Containing δ-Antagonist and κ-Agonist Pharmacophores Bridges δ2 and κ1 Opioid Receptor Phenotypes (2004)

To characterize delta- and kappa-opioid receptor phenotypes, bivalent ligands (KDAN series) containing delta-antagonist (naltrindole) and kappa(1)-agonist (ICI-199,441) pharmacophores were synthesized and evaluated by the intrathecal route using the mouse tail-flick assay and binding studies. The data have suggested that KDAN-18 (2) bridges phenotypic delta(2)- and kappa(1)-receptors. A conceptual model is presented to explain the organizational differences between the opioid receptors that give rise to the phenotypes (delta(1), delta(2), kappa(1), kappa(2)).
Immobilization and Hybridization of DNA on an Aluminum(III) Alkanebisphosphonate Thin Film with Electrogenerated Chemiluminescent Detection (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImmobilization and Hybridization of DNA on an Aluminum(III) Alkanebisphosphonate Thin Film with Electrogenerated Chemiluminescent DetectionXiao-Hong Xu and Allen J. BardCite this: J. Am. Chem. Soc. 1995, 117, 9, 2627–2631Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://pubs.acs.org/doi/10.1021/ja00114a027https://doi.org/10.1021/ja00114a027research-articleACS PublicationsRequest reuse permissionsArticle Views689Altmetric-Citations170LEARN 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
Augmented intrinsic activity of Factor VIIa by replacement of residues 305, 314, 337 and 374: evidence of two unique mutational mechanisms of activity enhancement (2004)

Coagulation Factor VIIa (FVIIa) lacks the ability to spontaneously complete the conversion to a fully active enzyme after specific cleavage of an internal peptide bond (Arg152-Ile153) in the zymogen. Recently, several variants of FVIIa with enhanced intrinsic activity have been constructed. The in vitro characterization of these variants has shed light on molecular determinants that put restrictions on FVIIa in favour of a zymogen-like conformation and warrants continued efforts. Here we describe a new FVIIa variant with high intrinsic activity containing the mutations Leu305-->Val, Ser314-->Glu, Lys337-->Ala, and Phe374-->Tyr. The variant, called FVIIa(VEAY), processes a tripeptidyl substrate very efficiently because of an unprecedented, 5.5-fold lowering of the K(m) value. Together with a 4-fold higher substrate turnover rate this gives the variant a catalytic efficiency 22 times that of wild-type FVIIa, which is reflected in a considerably enhanced susceptibility to inhibition by antithrombin and other inhibitors. For instance, the affinity of FVIIa(VEAY) for the S1 probe and inhibitor p -aminobenzamidine is represented by an 8-fold lower K(i) value compared with that of FVIIa. Activation of Factor X in solution occurs about 10 times faster with FVIIa(VEAY) than with FVIIa, due virtually exclusively to an increased kcat value. The high activity of FVIIa(VEAY) is not accompanied by an increased burial of the N-terminus of the protease domain. A comparison of the kinetic parameters and molecular properties of FVIIa(VEAY) with those of the previously described mutant V158D/E296V/M298Q-FVIIa (FVIIa(IIa)), and the locations of the substitutions in the two variants, reveals what appear to be two profoundly different structural mechanisms dictating improvements in enzymic performance.