gebhart/patrepeval huggingface dataset:
N-Acetylglucosamine Inhibits T-helper 1 (Th1)/T-helper 17 (Th17) Cell Responses and Treats Experimental Autoimmune Encephalomyelitis (2011)

Current treatments and emerging oral therapies for multiple sclerosis (MS) are limited by effectiveness, cost, and/or toxicity. Genetic and environmental factors that alter the branching of Asn (N)-linked glycans result in T cell hyperactivity, promote spontaneous inflammatory demyelination and neurodegeneration in mice, and converge to regulate the risk of MS. The sugar N-acetylglucosamine (GlcNAc) enhances N-glycan branching and inhibits T cell activity and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Here, we report that oral GlcNAc inhibits T-helper 1 (Th1) and T-helper 17 (Th17) responses and attenuates the clinical severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE when administered after disease onset. Oral GlcNAc increased expression of branched N-glycans in T cells in vivo as shown by high pH anion exchange chromatography, MALDI-TOF mass spectroscopy and FACS analysis with the plant lectin l-phytohemagglutinin. Initiating oral GlcNAc treatment on the second day of clinical disease inhibited MOG-induced EAE as well as secretion of interferon-γ, tumor necrosis factor-α, interleukin-17, and interleukin-22. In the more severe 2D2 T cell receptor transgenic EAE model, oral GlcNAc initiated after disease onset also inhibits clinical disease, except for those with rapid lethal progression. These data suggest that oral GlcNAc may provide an inexpensive and nontoxic oral therapeutic agent for MS that directly targets an underlying molecular mechanism causal of disease.
Multiple β-Ketothiolases Mediate Poly(β-Hydroxyalkanoate) Copolymer Synthesis in Ralstonia eutropha (1998)

Polyhydroxyalkanoates (PHAs) are a class of carbon and energy storage polymers produced by numerous bacteria in response to environmental limitation. The type of polymer produced depends on the carbon sources available, the flexibility of the organism's intermediary metabolism, and the substrate specificity of the PHA biosynthetic enzymes. Ralstonia eutropha produces both the homopolymer poly-beta-hydroxybutyrate (PHB) and, when provided with the appropriate substrate, the copolymer poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV). A required step in production of the hydroxyvalerate moiety of PHBV is the condensation of acetyl coenzyme A (acetyl-CoA) and propionyl-CoA to form beta-ketovaleryl-CoA. This activity has generally been attributed to the beta-ketothiolase encoded by R. eutropha phbA. However, we have determined that PhbA does not significantly contribute to catalyzing this condensation reaction. Here we report the cloning and genetic analysis of bktB, which encodes a beta-ketothiolase from R. eutropha that is capable of forming beta-ketovaleryl-CoA. Genetic analyses determined that BktB is the primary condensation enzyme leading to production of beta-hydroxyvalerate derived from propionyl-CoA. We also report an additional beta-ketothiolase, designated BktC, that probably serves as a secondary route toward beta-hydroxyvalerate production.
Joint optimal channel base station and power assignment for wireless access (1996)

The provision of personal communication services is the goal of the evolution of integrated communication systems. The fundamental problem underlying any phase (hand-off, new connection, etc.) of a dynamic resource allocation algorithm in a wireless network is to assign transmission powers, forward (downstream) and reverse (upstream) channels, and base stations such that every mobile of the system can establish a connection. Each one of these problems separately has been studied extensively. We consider the joint problem in a system with two base stations. An algorithm that achieves the optimal assignment is provided. It involves the computation of a maximum matching in a graph that captures the topological characteristics of the mobile locations. The traffic capacities, in terms of expected number of connections per channel, of the forward and reverse channel are obtained and compared, for both cases of power control and nonpower control. It turns out that when the transmission power is fixed, the capacities of the forward and reverse channel are different, while when power control is allowed they are the same. For systems with two mobiles the capacities of the forward and reverse channels are studied analytically. Finally, several versions of the two-way channel assignment problem are studied.
Self-exciting, self-sensing PbZr0.53Ti0.47O3∕SiO2 piezoelectric microcantilevers with femtogram/Hertz sensitivity (2006)

Piezoelectric microcantilever sensors (PEMSs) consisting of a piezoelectric layer bonded to a nonpiezoelectric layer offer the advantages of electrical self-actuation and self-detection. Here we report PEMSs 60–300μm in length fabricated from 1.5-μm-thick sol-gel PbZr0.53Ti0.47O3 (PZT) films with a 2μm grain size, a dielectric constant of 1600, and a saturation polarization of 55±5μC∕cm2. The PEMSs exhibited up to four resonance peaks with quality factors Q ranging from 120 to 320. In humidity sensing tests, a PEMS with a 60×25μm PZT∕SiO2 section and a 24×20μm SiO2 extension exhibited 1×10−15g∕Hz mass sensitivity, two orders of magnitude better than the sensitivity of the current PZT PEMS.
Small Molecule Ligands of the Human Melanocortin-4 Receptor (2007)

Genetic and pharmacological studies, involving both animals and humans, suggest that the central MC4 receptor plays a key role in homeostatic control, most probably via regulation of appetite and energy expenditure. This has stimulated intense research efforts in the field of drug discovery to identify MC4 receptor agonists and antagonists for the therapeutic treatment of obesity and diseases associated with loss of body weight. This article constitutes a near comprehensive review of the published scientific literature on small molecule ligands of the hMC4 receptor since 2002.
Oxidative Metabolism of Murine Macrophages (1994)

This unit describes two simple and straightforward microassays that can be used to measure the levels of NO(2)(-) and O(2)(-), respectively that are generated by a small number of immunologically-stimulated macrophages. Detection of these products may be used to identify cytokine(s), microbe(s), or microbial products(s) that regulate oxidative metabolism and effector activity. Although a number of other reliable and sensitive methods are available for assaying these two oxidative metabolites, the microassays described here require little time, technical expertise, or materials. It is not clear at present whether human monocytes/macrophages can also produce NO(2)(-). These protocols are therefore restricted to mouse macrophages.
Biochemical characterization of the initial steps of the Kennedy pathway in Trypanosoma brucei: the ethanolamine and choline kinases (2008)

Ethanolamine and choline are major components of the trypanosome membrane phospholipids, in the form of GPEtn (phosphatidylethanolamine) [corrected] and GPCho (phosphatidylcholine) [corrected] . Ethanolamine is also found as an integral component of the GPI (glycosylphosphatidylinositol) anchor that is required for membrane attachment of cell-surface proteins, most notably the variant-surface glycoproteins. The de novo synthesis of GPEtn and GPCho starts with the generation of phosphoethanolamine and phosphocholine by ethanolamine and choline kinases via the Kennedy pathway. Database mining revealed two putative C/EKs (choline/ethanolamine kinases) in the Trypanosoma brucei genome, which were cloned, overexpressed, purified and characterized. TbEK1 (T. brucei ethanolamine kinase 1) was shown to be catalytically active as an ethanolamine-specific kinase, i.e. it had no choline kinase activity. The K(m) values for ethanolamine and ATP were found to be 18.4+/-0.9 and 219+/-29 microM respectively. TbC/EK2 (T. brucei choline/ethanolamine kinase 2), on the other hand, was found to be able to phosphorylate both ethanolamine and choline, even though choline was the preferred substrate, with a K(m) 80 times lower than that of ethanolamine. The K(m) values for choline, ethanolamine and ATP were 31.4+/-2.6 microM, 2.56+/-0.31 mM and 20.6+/-1.96 microM respectively. Further substrate specificity analysis revealed that both TbEK1 and TbC/EK2 were able to tolerate various modifications at the amino group, with the exception of a quaternary amine for TbEK1 (choline) and a primary amine for TbC/EK2 (ethanolamine). Both enzymes recognized analogues with substituents on C-2, but substitutions on C-1 and elongations of the carbon chain were not well tolerated.
RECOGNIZING THE ANXIOUS FACE OF DEPRESSION (2002)

"Anxious depression" is used variably both by researchers and clinicians to describe admixtures of anxiety and depressive symptoms. The authors sought to determine the best model for conceptualizing anxious depression by studying a sample of depressed patients referred to a tertiary referral unit. Anxiety and depression were assessed using a comprehensive set of mixed symptoms that were subsequently refined to provide separate anxiety and depressive factors, and patients were trichotomized into groups of low, medium, and high anxiety on the basis of their total anxiety factor scores. Associations between the constructs of anxiety and depression in different depressive subgroups were explored, and the severity of depressive symptoms and other clinical variables across the three anxiety groupings was assessed. Depression variables were not linearly associated in a consistent pattern with anxiety-defined groups, arguing against a simple interdependence model driven by a higher-order variable such as depression severity. By contrast, the state anxiety categories were linked strongly with lifetime anxiety disorder prevalence, with some associations linear and with others evidencing a trend break association. The authors found support for a model of anxious depression, whereby anxiety both predisposes to nonmelancholic depression and contributes to its presentation by shaping its clinical features. Such a model and its definition assist in clarifying the cause of anxious depression and its treatment.
SP 800-38A 2001 edition. Recommendation for Block Cipher Modes of Operation: Methods and Techniques (2001)

This recommendation defines five confidentiality modes of operation for use with an underlying symmetric key block cipher algorithm: Electronic Codebook (ECB), Cipher Block Chaining (CBC), Cipher Feedback (CFB), Output Feedback (OFB), and Counter (CTR). Used with an underlying block cipher algorithm that is approved in a Federal Information Processing Standard (FIPS), these modes can provide cryptographic protection for sensitive, but unclassified, computer data.
Drug Targets in Severe Acute Respiratory Syndrome (SARS) Virus and other Coronavirus Infections (2009)

Coronaviruses are important human and animal pathogens of the order Nidovirales. Several new members were discovered following the emergence of SARS-CoV in human populations, including two human coronaviruses and several animal coronaviruses. They cause respiratory and gastrointestinal illnesses and have been found in the brains of patients with multiple sclerosis. The high mortality of SARS, the identification of a natural reservoir, and the well-founded fear of provoking antibody-enhanced disease as a result of vaccination fueled the ongoing efforts in anti-coronavirus drug discovery. This review presents the results of current research.
1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesics (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1-(3,4-Dichlorobenzamidomethyl)cyclohexyldimethylamine and related compounds as potential analgesicsN. J. Harper, G. B. A. Veitch, and D. G. WibberleyCite this: J. Med. Chem. 1974, 17, 11, 1188–1193Publication Date (Print):November 1, 1974Publication History Published online1 May 2002Published inissue 1 November 1974https://pubs.acs.org/doi/10.1021/jm00257a012https://doi.org/10.1021/jm00257a012research-articleACS PublicationsRequest reuse permissionsArticle Views394Altmetric-Citations39LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
T-DNA from Agrobacterium Ti plasmid is in the nuclear DNA fraction of crown gall tumor cells (1980)

The crown gall teratoma tumor line BT37, incited by Agrobacterium tumefaciens strain T37, has been found to contain part of the tumor-inducing plasmid, pTi T37, of the inciting strain. This foreign DNA segment, called T-DNA, is maintained at several copies per diploid tumor cell. We have examined subcellular DNA fractions from this tumor line in an effort to determine whether T-DNA is in chloroplasts, mitochondria, or nuclei. Tumor cell chloroplast DNA exhibited EcoRI and Bst I endonuclease cleavage patterns identical to those of normal tobacco chloroplast DNA. Tumor cell mitochondrial DNA exhibited a complex Bst I cleavage pattern that did not differ detectably from that of normal tobacco mitochondrial DNA. Southern blots of tumor chloroplast and mitochondrial cleavage products did not hybridize with labeled pTi T37 DNA, whereas blots of tumor cell nuclear DNA cleavage products hybridized strongly. We conclude that T-DNA is located not in chloroplasts or mitochondria but rather in the nuclear fraction of this tumor line.
Effect of Magnesium Ions on Oriented Growth of Calcite on Carboxylic Acid Functionalized Self-Assembled Monolayer (2003)

The combined effect of templating and solution additives on calcite crystallization was studied. Self-assembled monolayers of mercaptoundecanoic acid supported on silver, as templates, induced the uniform, oriented nucleation of calcite from the (012) plane. The presence of Mg2+ in the crystallizing solution affected the crystal growth dramatically, due to the selective Mg binding to the calcite planes roughly parallel to the c-axis. Highly homogeneous arrays of oriented crystals with characteristic sizes, shapes, and morphology, depending on the relative concentration of Mg and Ca ions, were synthesized.
Modification of Maternal and Congenital Cytomegalovirus Infection by Anti–Glycoprotein B Antibody Transfer in Guinea Pigs (2001)

Prepregnancy human and guinea pig cytomegalovirus immunity reduces rates of congenital infection in subsequent pregnancies. Inbred JY-9 strain guinea pigs were used to study the role of hyperimmune anti-glycoprotein B (gB) serum in modification of congenital infection in early pregnancy. Significantly shorter duration of primary maternal viremia and fewer pregnancy losses occurred in passively immunized dams, compared with nonimmune dams. Placentas from recipients of negative control serum were smaller and had marked mononuclear cell infiltrates and focal necrosis and more viral foci than did those from recipients of anti-gB hyperimmune serum. Significantly higher intrauterine growth retardation occurred in pups of negative control serum recipients than in pups of passively immunized dams. Significantly higher proportions of pups and placentas from recipients of negative control serum were positive on viral culture than from passively immunized dams. Thus, anti-gB passive immunization decreased fetal infection and intrauterine growth retardation, shortened maternal viremia, and reduced pregnancy losses and placental inflammation and infection.
Small molecule microarray screening methodology based on surface plasmon resonance imaging (2015)

In order to increase the scope and utility of small molecule microarrays (SMMs) we have combined SMMs and SPRi to screen small molecule antagonists against protein targets. Several small molecules, including immunosuppressive drugs (rapamycin and FK506) and reported inhibitors (FOBISIN and Blapsin) of 14-3-3ζ proteins have been used to validate this technology. Furthermore, a small library of isatin derivatives have been synthesized and screened on developed platform against 14-3-3ζ protein. Three molecules, derived from the endogenous intermediate isatin termed, FZIB-35, FZIB-36 and FZIB-38 were identified as novel inhibitors which shows significant interaction with 14-3-3ζ. A mutation in the binding groove of 14-3-3ζ, (K49E), almost abolishes the binding of these compounds to 14-3-3ζ protein. To exclude the probability of false positives, two more purified proteins (PtpA and BirA) were also tested. Furthermore, in order to confirm the binding pocket specificity, competition assay against R18 peptide was also carried out on presented platform. We show that SMMs in combination with SPRi are a powerful method to identify lead compounds in high throughput manner without the need to develop an activity based assay. Keywords: Small molecule microarray, Surface plasmon resonance, 14-3-3ζ protein, Isatin and ligand–protein interaction
Report 33: Modelling the allocation and impact of a COVID-19 vaccine (2020)

Several SARS-CoV-2 vaccine candidates are now in late-stage trials, with efficacy and safety results expected by the end of 2020. Even under optimistic scenarios for manufacture and delivery, the doses available in 2021 are likely to be limited. Here we identify optimal vaccine allocation strategies within and between countries to maximise health (avert deaths) under constraints on dose supply. We extended an existing mathematical model of SARS-CoV-2 transmission across different country settings to model the public health impact of potential vaccines, using a range of target product profiles developed by the World Health Organization. We show that as supply increases, vaccines that reduce or block infection – and thus transmission – in addition to preventing disease have a greater impact than those that prevent disease alone, due to the indirect protection provided to high-risk groups. We further demonstrate that the health impact of vaccination will depend on the cumulative infection incidence in the population when vaccination begins, the duration of any naturally acquired immunity, the likely trajectory of the epidemic in 2021 and the level of healthcare available to effectively treat those with disease. Within a country, we find that for a limited supply (doses for &lt;20% of the population) the optimal strategy is to target the elderly and other high-risk groups. However, if a larger supply is available, the optimal strategy switches to targeting key transmitters (i.e. the working age population and potentially children) to indirectly protect the elderly and vulnerable. Given the likely global dose supply in 2021 (2 billion doses with a two-dose vaccine), we find that a strategy in which doses are allocated to countries in proportion to their population size is close to optimal in averting deaths. Such a strategy also aligns with the ethical principles agreed in pandemic preparedness planning.
Comorbidity (1999)

We review recent research on the prevalence, causes, and effects of diagnostic comorbidity among the most common groups of child and adolescent psychiatric disorders; anxiety disorders, depressive disorders, attention deficit hyperactivity disorders, oppositional defiant and conduct disorders, and substance abuse. A meta‐analysis of representative general population studies provides estimates of the strength of associations between pairs of disorders with narrower confidence intervals than have previously been available. Current evidence convincingly eliminates methodological factors as a major cause of comorbidity. We review the implications of comorbidity for understanding the development of psychopathology and for nosology.
Theory and group velocity of ultrashort, tightly focused laser pulses (1995)

The wave equation describing an ultrashort, tightly focused laser pulse in vacuum is solved analytically. Plasma dispersive effects are also included. Based on exact short-pulse solutions, analytical expressions are obtained for the pulse-length evolution, the pulse centroid motion, and the group velocity. Approximate short-pulse solutions are obtained to arbitrary order in the parameter λ/2πL &lt; 1, where λ is the pulse wavelength and L is the length of the pulse envelope. Comparisons are made to the solutions of the paraxial wave equation and to numerical solutions of the full wave equation. The exact analytical expression for the pulse group velocity vg, which is correctly determined from the motion of the pulse centroid, is in excellent agreement with the numerical solution. In vacuum, 1 − vg/c ≅ (λ/2πr0)2, where r0 is the laser spot size at focus. Estimates for the quantity 1 − vg/c, based on the paraxial wave equation, are found to be in error by a factor of 2.
Iron-regulated Outer-membrane Proteins of Escherichia coli Strains Associated with Enteric or Extraintestinal Diseases of Man and Animals (1988)

The SDS-PAGE patterns of the iron-regulated outer-membrane proteins from 70 strains of Escherichia coli isolated from various human and animal infections were analysed and the nature of the siderophores produced was examined. Iron-regulated 81 kDa and 74 kDa protein bands seen in SDS-PAGE gels were characterized further by immunoblotting using anti-81 kDa and anti-74 kDa (Cir) sera. The results showed considerable differences between the patterns of the iron-regulated outer-membrane proteins exhibited by the different strains. Nevertheless, three distinct and characteristic profiles, based on the most prominent bands expressed, could be identified, although not all strains produced patterns which matched with one of these. These results suggest the possibility of using the pattern of iron-regulated outer-membrane proteins expressed, as well as siderophores produced, as a new set of markers to characterize groups of pathogenic E. coli.
Molecular Cloning of the Acetylcholine Receptor (1983)

Acetylcholine (ACh) mediates synaptic transmission at the vertebrate neuromuscular junction. The synthesis and properties of the molecular components that subserve transmission at this synapse are determined by the interaction of nerve and muscle. In this respect, the neuromuscular junction may be typical of other synapses that are formed and stabilized through appropriate interaction of the pre- and postsynaptic cells. To study the mechanisms involved in synaptogenesis, we first chose to study the properties and regulation of one component of the transmission machinery, the receptor for ACh. This multimeric transmembrane glycoprotein resides in the postsynaptic membrane where it functions to convert binding of ACh into a change in the transmembrane potential.