gebhart/patrepeval huggingface dataset:
Structural analysis of human and murine flt3 ligand genomic loci. (1995)

Both the murine and human genomic loci that encode flt3 ligand have been cloned. flt3 ligand is a hematopoietic growth factor that stimulates the proliferation of stem and progenitor cells. The portions of the murine and human flt3 ligand genomic loci encompassing the coding region of the protein are approximately 4.0 kb and 5.9 kb, respectively. The human genomic locus is larger as a result of the presence of repeated sequences within introns I, II, IV, V and VI. The transmembrane isoform of the murine and human flt3 ligand proteins are each encoded within seven exons (1-5 + 7 and 8). Analyses of flt3 ligand cDNA clones show that alternative splicing of a putative sixth exon results in the generation of a soluble form of the flt3 ligand protein. The sizes of each of the exons are well conserved between species. Murine and human flt3 genomic loci have a similar exon: intron structure compared to the genomic loci encoding Steel factor and colony stimulating factor 1. These proteins, which appear to be ancestrally related, are hematopoietic growth factors that stimulate cells via specific and structurally related tyrosine kinase receptors on the cell surface.
Abstracts (1990)

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Spectroscopic and Functional Properties of Novel 2[4Fe-4S] Cluster-containing Ferredoxins from the Green Sulfur Bacterium Chlorobium tepidum (2001)

Two distinct ferredoxins, Fd I and Fd II, were isolated and purified to homogeneity from photoautotrophically grown Chlorobium tepidum, a moderately thermophilic green sulfur bacterium that assimilates carbon dioxide by the reductive tricarboxylic acid cycle. Both ferredoxins serve a crucial role as electron donors for reductive carboxylation, catalyzed by a key enzyme of this pathway, pyruvate synthase/pyruvate ferredoxin oxidoreductase. The reduction potentials of Fd I and Fd II were determined by cyclic voltammetry to be -514 and -584 mV, respectively, which are more electronegative than any previously studied Fds in which two [4Fe-4S] clusters display a single transition. Further spectroscopic studies indicated that the CD spectrum of oxidized Fd I closely resembled that of Fd II; however, both spectra appeared to be unique relative to ferredoxins studied previously. Double integration of the EPR signal of the two Fds yielded approximately approximately 2.0 spins per molecule, compatible with the idea that C. tepidum Fd I and Fd II accept 2 electrons upon reduction. These results suggest that the C. tepidum Fd I and Fd II polypeptides each contain two bound [4Fe-4S] clusters. C. tepidum Fd I and Fd II are novel 2[4Fe-4S] Fds, which were shown previously to function as biological electron donors or acceptors for C. tepidum pyruvate synthase/pyruvate ferredoxin oxidoreductase (Yoon, K.-S., Hille, R., Hemann, C. F., and Tabita, F. R. (1999) J. Biol. Chem. 274, 29772-29778). Kinetic measurements indicated that Fd I had approximately 2.3-fold higher affinity than Fd II. The results of amino acid sequence alignments, molecular modeling, oxidation-reduction potentials, and spectral properties strongly indicate that the C. tepidum Fds are chimeras of both clostridial-type and chromatium-type Fds, suggesting that the two Fds are likely intermediates in the evolutional development of 2[4Fe-4S] clusters compared with the well described clostridial and chromatium types.
N-alkylated aminopyrazines for use as hydrophilic optical agents (2009)

Rapid assessment of glomerular filtration rate (GFR), which measures the amount of plasma filtered through the kidney within a given time, would greatly facilitate monitoring of renal function for patients at the bedside in the clinic. In our pursuit to develop exogenous fluorescent tracers for real-time monitoring of renal function by optical methods, N-alkylated aminopyrazine dyes and their hydrophilic conjugates based on poly (ethylene glycol) (PEG) were synthesized via reductive amination as the key step. Photophysical properties indicated a bathochromic shift on the order of 50 nm in both absorption and emission compared to naked aminopyrazines which could be very useful in enhancing both tissue penetration as well as easier detection methods. Structure-activity relationship (SAR) and pharmacokinetic (PK) studies, and the correlation of in vivo optical data with plasma PK for measurement of clearance (and hence GFR) are focus of the current investigation.
Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference (2007)

Although published works rarely include causal estimates from more than a few model specifications, authors usually choose the presented estimates from numerous trial runs readers never see. Given the often large variation in estimates across choices of control variables, functional forms, and other modeling assumptions, how can researchers ensure that the few estimates presented are accurate or representative? How do readers know that publications are not merely demonstrations that it is possible to find a specification that fits the author's favorite hypothesis? And how do we evaluate or even define statistical properties like unbiasedness or mean squared error when no unique model or estimator even exists? Matching methods, which offer the promise of causal inference with fewer assumptions, constitute one possible way forward, but crucial results in this fast-growing methodological literature are often grossly misinterpreted. We explain how to avoid these misinterpretations and propose a unified approach that makes it possible for researchers to preprocess data with matching (such as with the easy-to-use software we offer) and then to apply the best parametric techniques they would have used anyway. This procedure makes parametric models produce more accurate and considerably less model-dependent causal inferences.
Conversion of Pollen Particles into Three-Dimensional Ceramic Replicas Tailored for Multimodal Adhesion (2013)

We report the first syntheses of three-dimensional (3D) nanocrystalline all-oxide replicas of pollen microparticles tailored for multimodal (bioenabled and synthetic) adhesion via use of a scalable, highly conformal surface sol–gel (SSG) coating process. High-fidelity replication allowed the pollen-shaped oxide microparticles to be utilized for adhesion via tailorable short-range (∼10 nm) van der Waals (VDW) attraction, with the magnitude of such VDW-based adhesion influenced by the nanoscale topography of surface features retained by the replicas. Conversion of the pollen into ferrimagnetic (Fe3O4) microparticle replicas allowed the use of magnetic attraction at short and long ranges (up to ∼1 mm). By selecting pollen particles with particular surface features and by SSG-enabled conversion of such pollen into 3D nanocrystalline replicas composed of an appropriate type and amount of magnetic oxide, adhesive microparticles with tunable short- and long-range attractive forces can be generated.
Poly(Malic Acid) Nanoconjugates Containing Various Antibodies and Oligonucleotides for Multitargeting Drug Delivery (2008)

Nanoconjugates are emerging as promising drug-delivery vehicles because of their multimodular structure enabling them to actively target discrete cells, pass through biological barriers and simultaneously carry multiple drugs of various chemical nature. Nanoconjugates have matured from simple devices to multifunctional, biodegradable, nontoxic and nonimmunogenic constructs, capable of delivering synergistically functioning drugs in vivo. This review mainly concerns the Polycefin family of natural-derived polymeric drug-delivery devices as an example. This type of vehicle is built by hierarchic conjugation of functional groups onto the backbone of poly(malic acid), an aliphatic polyester obtained from the microorganism Physarum polycephalum. Particular Polycefin variants target human brain and breast tumors implanted into animals specifically and actively and could be detected easily by noninvasive imaging analysis. Delivery of antisense oligonucleotides to a tumor-specific angiogenic marker using Polycefin resulted in significant inhibition of tumor angiogenesis and increase of animal survival.
Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells (2014)

The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor.
Conformational Properties of Molecules by ab Initio Quantum Mechanical Energy Minimization (1985)

The recent literature on the determination of minimum energy conformations by ab initio quantum mechanical techniques is reviewed. The availability of computer-coded analytical first and second derivatives of the Hartree-Fock energy makes possible calculations that will be of significant assistance in structure determination of molecules. A short review of recent progress in empirical energy minimization and molecular dynamics is provided.
Diastereoselective Synthesis of Conformationally Restricted Dinucleotides Featuring Canonical and Noncanonical α/β Torsion Angle Combinations(α,β‐D‐CNA) (2006)

Abstract The synthesis of the four possible diastereoisomers of α,β‐D‐CNA 5′‐XT (X = A, T, G and C) building units of nucleic acids, in which the α and β torsional angles are stereocontrolled by a dioxaphosphorinane ring structure (D‐CNA family) is described. The crystal structure analysis of the ( R C5′ , S P )‐configured α,β‐D‐CNA TT dimer demonstrates that the α and β torsional angles are restricted to the canonical {gauche(–), trans } conformation typically observed in DNA duplexes. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
ChemInform Abstract: Alkali Metal Fluorides as Efficient Fluorinating Agents. Enantiocontrolled Synthesis of 2‐Fluoroalkyl Carboxylates and 1‐ Fluoroalkyl Benzenes. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Effects of p56lck deficiency on the growth and cytolytic effector function of an interleukin-2-dependent cytotoxic T-cell line. (1992)

The growth, differentiation, and functional activities of antigen-stimulated T lymphocytes are regulated by the interaction of the T-cell-derived cytokine, interleukin-2 (IL-2), with the high-affinity IL-2 receptor (IL-2R). IL-2R occupancy initiates a rapid increase in intracellular protein tyrosine phosphorylation, suggesting that a receptor-coupled protein tyrosine kinase (PTK) serves as a proximal signaling element for the IL-2R. Previous studies implicated the src-family kinase, p56lck, as a potential IL-2R-linked signal transducer. In this study, we have characterized a spontaneous variant of the IL-2-dependent cytotoxic T-cell line, CTLL-2, which contains no detectable lck-derived mRNA transcripts, protein, or PTK activity. The p56lck-deficient CTLL-2 cells retained strict dependence on IL-2 for both viability and growth, indicating that p56lck activity was not required for the transduction of IL-2-mediated mitogenic signals. However, the p56lck-deficient cells exhibited a moderate decrease in their rate of IL-2-dependent proliferation. In contrast to this relatively modest proliferative defect, the p56lck-deficient cell line displayed a profound reduction in T-cell antigen receptor-dependent cytolytic effector functions. Both the proliferative and the cytolytic defects observed in the p56lck-deficient cells were completely reversed by transfection of these cells with a wild-type lck expression vector. These results indicate that p56lck expression is not obligatory for IL-2-mediated T-cell growth stimulation; however, this PTK plays a central role in the generation T-cell-mediated cytotoxic responses.
Venous haemodynamics of the upper extremity after subclavian vein thrombosis. (1990)

Late post-thrombotic complaints after subclavian vein thrombosis are reported with highly varying frequencies (8-80% severe disability). The therapeutic approach depends partly on this frequency. With the aim to evaluate late sequelae a questionnaire was answered by 26 patients with arm-shoulder symptoms leading to arm phlebography, but where the examination did not reveal any thrombi. 65% had remaining symptoms 2-9 years after the examination. 3 had to change profession. 36 patients with phlebographically shown subclavian vein thrombosis answered the same questionnaire. Only 9 (25%) had remaining symptoms and in 4 it was classified as mild, in 4 as moderate and only in 1 patient as severe leading to change of profession. Venous haemodynamics in the upper extremity were also studied in 3 groups of patients; I) healthy volunteers (n = 16 arms), II) patients with arm-shoulder disabilities with negative arm phlebography (n = 7 disabled arms, n = 7 non-disabled arms), III) patients with phlebographically verified subclavian vein thrombi (n = 10 arms with DVT, n = 8 arms without DVT). Strain gauge plethysmography was used measuring venous capacity and maximal venous outflow. Venous pressure measurements were made both with the arms in a resting position and in a military position with and without work-load. Repeat phlebography of arms with symptoms were made. Maximal venous outflow was significantly lower in arms with previous subclavian vein thrombi (p less than 0.05) and venous pressure measurements with the arm in military position was significantly higher in those arms. However, no correlation between these measurements and the degree of arm disability was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
The expression of MAGE and SSX, and correlation of COX2, VEGF, and survivin in colorectal cancer. (2012)

Our results suggest that nuclear expression of survivin, lymph node metastasis, vascular and perineural invasion, and co-expression of MAGE and SSX may be associated with the metastasis of colorectal cancer to the liver.
Dissociation of influenza virus hemagglutinin and neuraminidase eliminates their intravirionic antigenic competition (1993)

When presented together on the intact influenza virus particle, the external hemagglutinin (HA) and neuraminidase (NA) antigens are competitive, with HA dominant over NA in both T- and B-cell priming (B. E. Johansson, T. M. Moran, and E. D. Kilbourne, Proc. Natl. Acad. Sci. USA 84:6869-6873, 1987). Dissociation and purification of HA and NA from virus and their injection separately or in combination into BALB/c mice eliminates their antigenic competition as measured by antibody response, confirming that it is their structural association that leads to what we have termed intravirionic antigenic competition. We discuss this phenomenon with respect to previously described intermolecular antigenic competition and with regard to its probable mechanism. Our findings are relevant to contemporary interest in viral vaccine vectors and multicomponent vaccines.
Parallels between Cancer and Infectious Disease (2014)

The status of the immune system affects and is affected by both cancer and chronic infection. Some molecular mechanisms of immunity are relevant to both disease states.
Serum Proteomics and Biomarker Discovery Across the Spectrum of Nonalcoholic Fatty Liver Disease (2009)

This proteomic analysis reveals important information regarding the pathogenesis/progression of NAFLD and NASH and demonstrates key changes in serum protein expression levels between control subjects and patients with different stages of fatty liver. Future validation of these potential biomarkers is needed such that these proteins may be used in place of liver biopsy to facilitate diagnosis and treatment of patients with NAFLD.
MarA-mediated overexpression of the AcrAB efflux pump results in decreased susceptibility to tigecycline in Escherichia coli (2007)

This study suggested that a loss of MarR functionality due to a frameshift mutation resulted in constitutive overproduction of MarA and AcrAB and, consequently, in decreased susceptibility to tigecycline in clinical isolates of E. coli.
Nephrocystin (2000)

Juvenile nephronophthisis, an autosomal recessive cystic kidney disease, is the primary genetic cause for chronic renal failure in children. The gene (NPHP1) for nephronophthisis type 1 has recently been identified. Its gene product, nephrocystin, is a novel protein of unknown function, which contains a src-homology 3 domain. To study tissue expression and analyze amino acid sequence conservation of nephrocystin, the full-length murine Nphp1 cDNA sequence was obtained and Northern and in situ hybridization analyses were performed for extensive expression studies. The results demonstrate widespread but relatively weak NPHP1 expression in the human adult. In the adult mouse there is strong expression in testis. This expression occurs specifically in cell stages of the first meiotic division and thereafter. In situ hybridization to whole mouse embryos demonstrated widespread and uniform expression at all developmental stages. Amino acid sequence conservation studies in human, mouse, and Caenorhabditis elegans show that in nephrocystin the src-homology 3 domain is embedded in a novel context of other putative domains of protein-protein interaction, such as coiled-coil and E-rich domains. It is concluded that for multiple putative protein-protein interaction domains of nephrocystin, sequence conservation dates back at least to Caenorhabditis elegans. The previously described discrepancy between widespread tissue expression and the restriction of symptoms to the kidney has now been confirmed by an in-depth expression study.
Cyclooxygenase as a Target in Lung Cancer (2004)

Preclinical studies suggest that cyclooxygenase (COX)-2 may be involved in the molecular pathogenesis of some types of lung cancer. Most of the available studies point to its involvement in non-small cell lung cancer. Survival of patients with non-small cell lung cancer expressing high levels of COX-2 is markedly reduced. Treatment of humans with the selective COX-2 inhibitor celecoxib augments the antitumor effects of chemotherapy in patients with non-small cell lung cancer. COX-2 has been shown to regulate some aspects of tumor-associated angiogenesis. Most of the results we have published point to effects on the regulation of vascular endothelial growth factor. However, prostaglandins derived from COX-2 affect other signaling pathways as well, such as the epidermal growth factor and its receptor. Others have recently shown that non-small cell lung cancer exhibits a COX-2 downstream enzyme expression pattern that is altered in lung tumor cells and tumor-supplying vessels. Therefore, COX-2 and prostaglandins may have a major impact on lung tumor progression and tumor-associated inflammation. Clinical trials currently underway are exploring the potential of targeting COX-2 in lung cancer.
MicroFootPrinter: a tool for phylogenetic footprinting in prokaryotic genomes (2006)

Phylogenetic footprinting is a method for the discovery of regulatory elements in a set of homologous regulatory regions, usually collected from multiple species. It does so by identifying the most conserved motifs in those homologous regions. This note describes web software that has been designed specifically for this purpose in prokaryotic genomes, making use of the phylogenetic relationships among the homologous sequences in order to make more accurate predictions. The software is called MicroFootPrinter and is available at http://bio.cs.washington.edu/software.html.