gebhart/patrepeval huggingface dataset:
Cloning and characterization of a cAMP-specific cyclic nucleotide phosphodiesterase (1998)

Cyclic nucleotide phosphodiesterases (PDEs) regulate intracellular levels of cAMP and cGMP by hydrolyzing them to their corresponding 5' monophosphates. We report here the cloning and characterization of a novel cAMP-specific PDE from mouse testis. This unique phosphodiesterase contains a catalytic domain that overall shares <40% sequence identity to the catalytic domain of all other known PDEs. Based on this limited homology, this new PDE clearly represents a previously unknown PDE gene family designated as PDE8. The cDNA for PDE8 is 3,678 nucleotides in length and is predicted to encode an 823 amino acid enzyme. The cDNA includes a full ORF as it contains an in-frame stop codon before the start methionine. PDE8 is specific for the hydrolysis of cAMP and has a Km of 0.15 microM. Most common PDE inhibitors are ineffective antagonists of PDE8, including the nonspecific PDE inhibitor 3-isobutyl-1-methylxanthine. Dipyridamole, however, an inhibitor that is generally considered to be relatively specific for the cGMP selective PDEs, does inhibit PDE8 with an IC50 of 4.5 microM. Tissue distribution studies of 22 different mouse tissues indicates that PDE8 has highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order. In situ hybridizations in testis, the tissue of highest expression, shows that PDE8 is expressed in the seminiferous epithelium in a stage-specific manner. Highest levels of expression are seen in stages 7-12, with little or no expression in stages 1-6.
Efficient combination of large DNA in vitro: in gel site specific recombination (IGSSR) of PAC fragments containing alpha satellite DNA and the human HPRT gene locus (1997)

In an attempt to combine a cloned genomic copy of a selectable gene with different cloned centromeric sequences to develop mammalian artificial chromosomes (MAC) we used site specific recombination mediated by purified Cre recombinase acting on the loxP sequence in PAC vector DNA. A new method was required to purify highly concentrated, virtually 100% intact PAC DNA which could be stored for a long period. Here we show the efficient linking of linearized PACs containing alpha satellite DNA from chromosomes X and 17 with sizes of 125 and 140 kb, respectively, to a 95 kb restriction fragment derived from a 175 kb PAC containing the intact human HPRT gene locus.
ChemInform Abstract: Perspectives in Supramolecular Chemistry: From Molecular Recognition Towards Self‐Organization (1995)

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.
High-affinity ssDNA inhibitors of the reverse transcriptase of type 1 human immunodeficiency virus (1995)

The reverse transcriptase (RT) of HIV-1 is a plausible target for therapeutic agents aimed at inhibiting propagation of the virus. We have used "irrational drug design", that is, combinatorial chemistry with oligonucleotide libraries, to identify high-affinity ligands aimed at HIV-1 RT. The methodology, termed SELEX (systematic evolution of ligands by exponential enrichment), was employed with a single-stranded DNA library. The selected ssDNA ligands bind HIV-1 RT with Kd values as low as 1 nM and inhibit the RNA-dependent DNA-polymerase activity of the enzyme with Ki values as low as 0.3 nM. We also demonstrate the high specificity of one ligand able to selectively discriminate between the reverse transcriptases of HIV-1, AMV, and MMLV. These ssDNA molecules may be useful as inhibitors or as models for the design of small molecule inhibitors of HIV-1 RT in vivo.
FADD: Essential for Embryo Development and Signaling from Some, But Not All, Inducers of Apoptosis (1998)

FADD (also known as Mort-1) is a signal transducer downstream of cell death receptor CD95 (also called Fas). CD95, tumor necrosis factor receptor type 1 (TNFR-1), and death receptor 3 (DR3) did not induce apoptosis in FADD-deficient embryonic fibroblasts, whereas DR4, oncogenes E1A and c-myc, and chemotherapeutic agent adriamycin did. Mice with a deletion in the FADD gene did not survive beyond day 11.5 of embryogenesis; these mice showed signs of cardiac failure and abdominal hemorrhage. Chimeric embryos showing a high contribution of FADD null mutant cells to the heart reproduce the phenotype of FADD-deficient mutants. Thus, not only death receptors, but also receptors that couple to developmental programs, may use FADD for signaling.
The Fully Informed Particle Swarm: Simpler, Maybe Better (2004)

The canonical particle swarm algorithm is a new approach to optimization, drawing inspiration from group behavior and the establishment of social norms. It is gaining popularity, especially because of the speed of convergence and the fact that it is easy to use. However, we feel that each individual is not simply influenced by the best performer among his neighbors. We, thus, decided to make the individuals "fully informed." The results are very promising, as informed individuals seem to find better solutions in all the benchmark functions.
IL-17A-Producing Tn cells escape thymic selection and regulate granulopoiesis in Rag-1−/− mice. (83.16) (2007)

Abstract Interleukin- (IL-) 23 and IL-17A play pivotal roles in the regulation of granulopoiesis in mice via a regulatory neutrostat feedback loop. Dendritic cells (DC) and macrophages release IL-23 in response to microbial products. IL-23 enhances the release of IL-17A from three Tn cell subsets, CD4−CD8−αβlow, CD4+CD8−αβ+ and γδ+. IL-17A levels correlate with neutrophil (PMN) and G-CSF levels in the blood. The feedback loop is closed by the trafficking of PMN’s into the tissues, their apoptosis and engulfment by resident DC, which curbs secretion of IL-23. As most granulopoiesis is controlled by T cells, athymic (nude) mice are neutropenic. However, Rag-1−/− mice have normal PMN numbers and if crossed onto a neutrophillic mouse background, remain neutrophilic, suggesting that immature T cells also regulate granulopoiesis. Here, we show that WT and Rag-1−/− mouse splenocytes secrete IL-17A without TCR cross-linking, and Tn cells are found in the thymus, spleen and MLN of both mouse models. Characterization of these cells places them into the DN1e category of prothymocytes which do not express classical lineage markers and are CD25−, CD117−, CD24− and CD44+. Adoptive transfer of Rag-1−/− thymocytes into nude mice rescued their neutropenia, with 99.8% of PMN’s being recipient derived. Thus, IL-17A-producing thymocytes are able to escape thymic selection and regulate granulopoiesis in the periphery of mice. Supported by NIH HL 73361
The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway in L6 cells between Ras and Raf (1994)

Glycogen synthase kinase-3 (GSK3) is inactivated in vitro by p70 S6 kinase or MAP kinase-activated protein kinase-1 beta (MAPKAP kinase-1 beta; also known as Rsk-2). Here we show that GSK3 isoforms are inhibited by 40% within minutes after stimulation of the rat skeletal-muscle cell line L6 with insulin-like growth factor-1 (IGF-1) or insulin. GSK3 was similarly inhibited in rabbit skeletal muscle after an intravenous injection of insulin. Inhibition resulted from increased phosphorylation of GSK3, probably at a serine/threonine residue(s), because it was reversed by incubation with protein phosphatase-2A. Rapamycin blocked the activation of p70 S6 kinase by IGF-1 in L6 cells, but had no effect on the inhibition of GSK3 or the activation of MAPKAP kinase-1 beta. In contrast, wortmannin, a potent inhibitor of PtdIns 3-kinase, prevented the inactivation of GSK3 and the activation of MAPKAP kinase-1 beta and p70 S6 kinase by IGF-1 or insulin. Wortmannin also blocked the activation of p74raf-1. MAP kinase kinase and p42 MAP kinase, but not the formation of GTP-Ras by IGF-1. The results suggest that the stimulation of glycogen synthase by insulin/IGF-1 in skeletal muscle involves the MAP-KAP kinase-1-catalysed inhibition of GSK3, as well as the previously described activation of the glycogen-associated form of protein phosphatase-1.
Scale-Up Strategies for Processing High-Rate Data Streams in System S (2009)

High performance stream processing is critical in sense-and-respond application domains – from environmental monitoring to algorithmic trading. In this paper, we focus on language and runtime support for improving the performance of sense-and-respond applications in processing data from high rate streams. The central tenet of this work is the definition of a streaming architectural pattern for these application domains and the programming model and the code generation framework to support it. Using IBM Research's System S middleware and the SPADE language, we demonstrate how to scale up a financial trading application.
Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection (2011)

Diarrhoea, as a common side effect of antibiotics, increases treatment costs and length of stay in acute healthcare facilities. One potential strategy to prevent this side effect is the concurrent use of probiotic bacteria or yeast. This review discusses the evidence for the efficacy of probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection; the potential mechanisms by which probiotics may work; their safety; what future research is required; and recommendations for use in clinical practice.
Tissue-specific Expression of Human Lipoprotein Lipase (1995)

Lipoprotein lipase (LPL) is a central enzyme in lipoprotein metabolism and is expressed predominantly in adipose tissue and muscle. In these tissues, the regulation of LPL is complex and often opposite in response to the same physiologic stimulus. In addition, much regulation of LPL occurs post-transcriptionally. The human LPL cDNA is characterized by a long 3'-untranslated region, which has two polyadenylation signals. In this report, human adipose tissue expressed two LPL mRNA species (3.2 and 3.6 kb) due to an apparent random choice of sites for mRNA polyadenylation, whereas human skeletal and heart muscle expressed predominantly the longer 3.6-kb mRNA form. To determine whether there was any functional significance to this tissue-specific mRNA expression, poly(A)-enriched RNA from adipose tissue and muscle were translated in vitro, and the poly(A)-enriched RNA from muscle was more efficiently translated into LPL protein. The increased translatability of the 3.6-kb form was also demonstrated by cloning the full-length 3.2- and 3.6-kb LPL cDNA forms, followed by in vitro translation of in vitro prepared transcripts. To confirm that this increased efficiency of translation occurred in vivo, Chinese hamster ovary cells were transfected with the 3.2- and 3.6-kb LPL cDNAs. Cells transfected with the 3.6-kb construct demonstrated increased LPL activity and synthesis, despite no increase in levels of LPL mRNA. Thus, human muscle expresses the 3.6-kb form of LPL due to a non-random choice of polyadenylation signals, and this form is more efficiently translated than the 3.2-kb form.
Synthesis of deuterium‐labelled drugs by hydrogen–deuterium (H–D) exchange using heterogeneous catalysis (2010)

Abstract Multi‐deuterium incorporations into drugs, such as theophylline, caffeine, valpromide, phenytoin, and trimethoprim, were post‐synthetically achieved by Pd/C‐, Pt/C‐, or/and Rh/C‐catalyzed hydrogen–deuterium exchange reactions under neutral conditions using deuterium oxide as the deuterium source in the presence of hydrogen gas. The present study offers facile and convenient methods for the preparation of highly deuterated medicines, which are expected to be used as long‐lasting medicines as well as internal standards for metabolic studies and for the quantitative analyses of the parent drugs.
Five-ring hollow-core photonic crystal fiber with 18 dB/km loss (2013)

A 19-cell hollow-core photonic crystal fiber reaching 1.8±0.5 dB/km loss at 1530 nm is reported. Despite expanded corner holes in the first ring adjacent to the core, and only five cladding rings, the minimum loss is close to the previously published record of 1.7 dB/km at a comparable wavelength, achieved in a fiber with seven cladding rings. Since each additional cladding ring requires a significant increase in fabrication time and complexity, it is highly desirable to use as few as possible while still achieving low loss. Modeling results confirm that further reducing cladding deformations would yield only a small decrease in loss. This demonstrates that loss comparable to the previously demonstrated lowest-loss bandgap fibers can be achieved with fiber structures that are significantly simpler and faster to fabricate.
Expression of a tumor-reactive antibody-interleukin 2 fusion protein after in vivo particle-mediated gene delivery. (1995)

We have used a particle-mediated gene transfer method to analyze the posttransfection expression pattern of an antibody-cytokine fusion protein (FP) in vivo. The FP, denoted CC49-IL2, consists of a single-chain antibody containing the antigen recognition domain from the murine monoclonal antibody CC49 (recognizing the tumor-associated antigen TAG-72), a human IgG1 constant heavy chain, and human interleukin-2 (IL-2). This FP can bind to TAG-72-expressing tumor cells and exhibits IL-2 activity. To induce systemic levels of this FP in vivo, we have transferred the FP gene into murine epidermal cells by direct delivery of DNA-coated gold particles using a transcutaneous "gene gun." After the pericutaneous delivery of the FP gene via gold particles, production of the exogenous FP was detected at the epidermal target site. The FP produced in vivo at the site of gene delivery has cytokine activity and antigen recognition capabilities similar to those present in CC49-IL2 FP purified from hybridoma culture supernatants in vitro. FP was also detectable in the serum from test animals treated with particle-mediated gene transfer. Time course experiments indicated that serum levels of FP reached a peak level within 8 hours after DNA delivery, whereas the epidermal target tissue levels continued to increase for 24 hours before plateauing. Our results indicate that exogenous protein levels consistent with immunotherapeutic effects of the FP can be readily achieved at the skin tissue site of gene delivery, with the potential for achieving therapeutic levels systemically.
APRIL and TACI interact with syndecan‐1 on the surface of multiple myeloma cells to form an essential survival loop (2009)

BLyS and APRIL share two receptors - transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA) - and BLyS binds to a third receptor, BAFF-R. We previously reported that TACI gene expression is a good indicator of a BLyS-binding receptor in human multiple myeloma cell lines (HMCLs), unlike BCMA, which is expressed by all HMCLs or BAFF-R which is typically not expressed by late-stage B cells. We hypothesised a link between APRIL and TACI through syndecan-1, similar to the situation reported for FGF and FGFR. We observed very strong binding of APRIL, but not BLyS, at the surface of all syndecan-1(+) HMCLs and primary multiple myeloma cells (MMC). All syndecan-1(+) HMCLs and MMC could also bind TACI-Fc, but not BCMA-Fc or BAFF-R-Fc molecules. Binding of APRIL or TACI-Fc was abrogated by heparin or cell pretreatment with heparitinase, which cleaves heparan sulfate chains. The growth factor activity of APRIL on MMC was also inhibited by heparin. Our data identify syndecan-1 as a co-receptor for APRIL and TACI at the cell surface of MMC, promoting the activation of an APRIL/TACI pathway that induces survival and proliferation in MMC.
The presence or absence of gp 120/gp 160 bands on indeterminate Western blota (1993)

King, R.; Frey, S.; Beisha, R.; de Perre, P. Van; Karita, E.; Allen, S. Author Information
Tailored Ligand Acceleration of the Cu-Catalyzed Azide−Alkyne Cycloaddition Reaction: Practical and Mechanistic Implications (2010)

Tris(heterocyclemethyl)amines containing mixtures of 1,2,3-triazolyl, 2-benzimidazoyl, and 2-pyridyl components were prepared for ligand acceleration of the copper-catalyzed azide-alkyne cycloaddition reaction. Two classes of ligands were identified: those that give rise to high reaction rates in coordinating solvents but inhibit the process when used in excess relative to copper and those that provide for fast catalysis in water and are not inhibitory in excess. Several "mixed" ligands were identified that performed well under both types of conditions. Kinetics measurements as a function of ligand:metal ratio and catalyst concentration were found to be consistent with an active Cu(2)L formulation. Since strongly bound chelating agents are not always the most effective, achieving optimal rates requires an assessment of the potential donor molecules in the reaction mixture. Simple rules are provided to guide the user in the choice of effective ligands and reaction conditions to suit most classes of substrates, solvents, and concentrations.
Fibroblast-collagen sponge interactions and the spatial deposition of newly synthesized collagen fibers in vitro and in vivo. (1984)

Fibroblast-collagen sponge interactions were studied in cell culture and dermal wound systems. In both models fibroblasts appear to adhere, attach and orient in the presence of type I collagen fibrils. In the presence of fibronectin, purified from bovine blood, adhesion and alignment of fibroblasts appeared to be enhanced as well as the deposition of thick collagen fibers. When collagen sponges were grafted onto full thickness dermal wounds the granulation tissue that was laid down within the collagen sponge appeared to differ from granulation tissue laid down below the collagen sponge or on similar wounds in the absence of a sponge. In the absence of a collagen sponge the granulation tissue is characterized by wavy collagen fibers that exhibit an extinction pattern characteristic of crimped fibers found in tendon when examined under polarized light. In contrast, collagen fibers laid down within the sponge appear to be highly oriented and lack evidence of crimp. These results suggest that the presence of a collagen matrix acts as a template that allows for the organized spatial deposition of newly synthesized collagen fibers. The enhanced biosynthesis of thick collagen fibers in the presence of a collagen sponge containing fibronectin may decrease the remodeling phase that is associated with dermal scarring.
Design and analysis of series elasticity in closed-loop actuator force control (2000)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2000.
Immunotherapy as a therapeutic treatment for neurodegenerative disorders (2003)

Human neurodegenerative illnesses such as Alzheimer's disease and Creutzfeldt-Jakob disease exact an enormous cost on individuals, families and society. For these and related disorders, current treatment is largely symptomatic without influencing the underlying disease process. Until recently, the development of immunotherapeutic approaches to neurodegenerative disorders had been almost completely ignored despite growing successes against other non-infectious diseases such as cancer. However, since Schenk and colleagues described the antibody-mediated clearance of amyloid plaques in a transgenic mouse model of Alzheimer's disease, a number of studies have confirmed the feasibility of this strategy for several neurodegenerative disorders including Huntington's disease and prion diseases. These reports offer the exciting prospect that either the immune system or its derivative components can be harnessed to fight the misfolded and/or aggregated proteins that accumulate in many neurodegenerative illnesses. If the remarkable power of clonal expansion, specificity and efficiency of the immune system can successfully inactivate these abnormal proteins, real hope exists that effective immunotherapeutic treatments for neurodegenerative illnesses may be available in the near future.
Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis. (1990)

Autoantibodies to three of the aminoacyl-transfer RNA (tRNA) synthetases have been reported (for histidine, threonine, and alanine). Most patients with these autoantibodies have polymyositis, and the majority also have interstitial lung disease. This study examined the question of whether autoantibodies to other aminoacyl-tRNA synthetases occur in the sera of myositis patients. We tested sera from patients with myositis with unidentified anticytoplasmic antibodies that immunoprecipitate tRNA for the ability to inhibit the aminoacyl-tRNA synthetases for the remaining 17 amino acids. Three sera showed strong inhibitory activity for a synthetase. OJ and NJ sera (and IgG) significantly inhibited isoleucyl-tRNA synthetase activity, each with 94% inhibition at the screening dilution, whereas other test sera and controls all inhibited less than 50%. OJ and NJ sera immunoprecipitated identical patterns of tRNA, and identical, complex patterns of high m.w. polypeptides that were consistent with the multienzyme synthetase complex of which isoleucyl-tRNA synthetase is a part. EJ serum (and IgG) significantly inhibited glycyl-tRNA synthetase, and immunoprecipitated a unique pattern of transfer RNA, and a strong predominant protein band of 77 kDa. These data strongly suggest that OJ and NJ have autoantibodies to isoleucyl-tRNA synthetase, and that EJ has antibodies to glycyl-tRNA synthetase. The findings of signs of muscle involvement in all three patients, and severe interstitial lung disease in OJ, strengthens the association of antisynthetases with these conditions.
Assessment of circulating serum DNA integrity in colorectal cancer patients. (2015)

Lower DNA integrity and the predominance of mononuclesomes in serum reveal high fragmentation of cfDNA in CRC patients.
A Molecular Railroad with Large Pores:  Synthesis and Structure of Ni(4,4‘-bpy)2.5(H2O)2(ClO4)2·1.5(4,4‘-bpy)·2H2O (1997)

The hydrothermal reaction of Ni(II) and the rodlike 4,4‘-bipyridine ligand yields an extended 1-D noninterpenetrated open framework resembling a railroad with large pores of 11 × 11 Å aperture. (4,4‘-Bipyridine is illustrated as lines, and Ni atoms are at the intersections.)
Achieving superresolution in near-field optical data readout systems using surface plasmons (2005)

The effects of surface plasmons and enhanced transmission on the readout contrast in a superresolving near-field optical data system are studied numerically using an exact Green’s tensor formulation. It is shown that plasmon effects can both help and hinder such a readout system, and the system geometry must be chosen carefully to produce optimal effects. Under certain conditions, the system can have a readout contrast approaching 50% and a resolution of at least λ∕3.