gebhart/patrepeval huggingface dataset:
Fibroblast Growth Factor Signaling in Metabolic Regulation (2016)

The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions.
Sensory Disturbances in Complex Regional Pain Syndrome: Clinical Observations, Autonomic Interactions, and Possible Mechanisms (2010)

Sympathetic neural activity might contribute to pain and sensory disturbances in CRPS by feeding into nociceptive circuits at the site of injury or elsewhere in the CRPS-affected limb, within the dorsal horn, or via thalamo-cortical projections.
Autophagy and pattern recognition receptors in innate immunity (2008)

Autophagy is a physiologically and immunologically controlled intracellular homeostatic pathway that sequesters and degrades cytoplasmic targets including macromolecular aggregates, cellular organelles such as mitochondria, and whole microbes or their products. Recent advances show that autophagy plays a role in innate immunity in several ways: (i) direct elimination of intracellular microbes by digestion in autolysosomes, (ii) delivery of cytosolic microbial products to pattern recognition receptors (PRRs) in a process referred to as topological inversion, and (iii) as an anti-microbial effector of Toll-like receptors and other PRR signaling. Autophagy eliminates pathogens in vitro and in vivo but, when aberrant due to mutations, contributes to human inflammatory disorders such as Crohn's disease. In this review, we examine these relationships and propose that autophagy is one of the most ancient innate immune defenses that has possibly evolved at the time of alpha-protobacteria-pre-eukaryote relationships, leading up to modern eukaryotic cell-mitochondrial symbiosis, and that during the metazoan evolution, additional layers of immunological regulation have been superimposed and integrated with this primordial innate immunity mechanism.
T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cell (2010)

The conversion of mature somatic cells into pluripotent stem cells, both by nuclear transfer and transduction with specific "reprogramming" genes, represents a major advance in regenerative medicine. Pluripotent stem cell lines can now be generated from an individual's own cells, facilitating the generation of immunologically acceptable stem cell-based therapeutics. Many cell types can undergo nuclear reprogramming, leading to the question of whether the identity of the reprogrammed cell of origin has a biological consequence. Peripheral blood, containing a mixture of T, B, NK, and myeloid cell types, represents one potential source of reprogrammable cells. In this study, we describe the unique case of mice derived from a reprogrammed T cell. These mice have prerearranged T-cell receptor (TCR) genes in all cells. Surprisingly, ≈50% of mice with prerearranged TCR genes develop spontaneous T cell lymphomas, which originate in the thymus. The lymphomas arise from developing T cells, and contain activated Notch1, similar to most human and mouse T-cell acute lymphoblastic lymphomas. Furthermore, lymphomagenesis requires the expression of both prerearranged TCRα and TCRβ genes, indicating a critical role for TCR signaling. Furthermore, inhibitors of multiple branches of TCR signaling suppress lymphoma growth, implicating TCR signaling as an essential component in lymphoma proliferation. The lymphomagenesis in mice derived from a reprogrammed T cell demonstrates the deleterious consequences of misregulation of the TCR rearrangement and signaling pathways and illustrates one case of cellular reprogramming where the identity of the cell of origin has profound consequences.
Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck (2010)

The efficacy of EGFR targeted therapies may be mediated, at least in part, by the immune system and the presence of the truncated EGFR variant, EGFRvIII, among other factors. Criteria to identify the subset of patients likely to be responsive to EGFR targeted therapies are needed.
The Homosexual Subject: Coming-Out as a Political Act (2007)

Drawing on Lacan's notion of the subject as a split and his four discursive forms, this paper identifies and examines three moments inherent to the coming out narratives. It is shown that two such moments, manifested as two forms of discourse-the hysteric's discourse and the master's discourse, open the possibility of political actions. The former adheres to a perpetual position to interrogating the established social‐symbolic order, whereas, the latter completes the steps of constituting and recognizing oneself in a new master's interpellation. The author then examines the form of and limitations to the political gestures entailed by the social constructionism and queer theory concerning the coming out processes: the social constructionist's insistence on completing the master's discourse and the queer gesture of rejecting any master and keeping the symbolic‐ ideological space open.
Dietary habits and mortality in 11 000 vegetarians and health conscious people: results of a 17 year follow up (1996)

In this cohort of health conscious individuals, daily consumption of fresh fruit is associated with a reduced mortality from ischaemic heart disease, cerebrovascular disease, and all causes combined.
The Synthesis of Several Acid Analogs of 2-Mercaptobenzimidazole1,2 (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of Several Acid Analogs of 2-Mercaptobenzimidazole1,2Theodore L. Rebstock, Charles D. Ball, Charles L. Hamner, and Harold M. SellCite this: J. Am. Chem. Soc. 1956, 78, 22, 5831–5832Publication Date (Print):November 1, 1956Publication History Published online1 May 2002Published inissue 1 November 1956https://pubs.acs.org/doi/10.1021/ja01603a032https://doi.org/10.1021/ja01603a032research-articleACS PublicationsRequest reuse permissionsArticle Views142Altmetric-Citations7LEARN 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
Purification and Biochemical Characterization of Recombinant N-Methylpurine-DNA Glycosylase of the Mouse (1994)

The mouse N-methylpurine-DNA glycosylase (MPG), responsible for the removal of most N-alkyladducts in DNA, was purified to homogeneity as a recombinant nonfusion protein from Escherichia coli. Only 10-15% of the protein was present in the soluble form in E. coli cells. The N-terminal amino acid sequence of the purified protein which lacks 48 residues from the amino terminus of the wild type protein was identical to that predicted from the nucleotide sequence. The glycosylase hydrolyzes 3-methyladenine (m3A), 7-methylguanine(m7G), and 3-methylguanine (m3G) from DNA, and the Km and kcat values were 130 nM and 0.8 min-1 for m3A, and 860 nM and 0.2 min-1 for m7G, respectively, when methylated calf thymus DNA was used as the substrate. A comparison of kcat/Km values for different bases indicates that the enzyme was more efficient in excising both m3A and m3G than m7G from methylated DNA. The enzyme showed moderate binding affinities (KA) for both methylated (5.8 x 10(7) M-1) and nonmethylated DNAs (4.2 x 10(7) M-1). The mouse protein has an extinction coefficient E280nm1% of 10.5 and a pI of 9.3. The enzyme activity was optimal in the presence of 100 mM NaCl, with a broad pH optimum of 8.5-9.5. The enzymatic release of both m3A and m7G was stimulated 50-75% by 0.5 mM MgCl2 and 0.02 mM spermine but inhibited by higher concentrations of these agents. Product inhibition by 40-50% of the reaction occurred in the presence of 10 mM m3A or m7G. However, 1.0 mM m3A stimulated release of m7G. The enzyme was inhibited by 60% in the presence of 0.9 mg/mL DNA which, at the same time, protected it from thermal inactivation.
Enzyme-linked immunosorbent assay for detecting antibodies to Borna disease virus-specific proteins (1995)

Borna disease virus is a unique neurotropic RNA virus that causes neurologic disease in a wide variety of animal hosts. We established an enzyme-linked immunosorbent assay for the detection of antibodies to Borna disease virus on the basis of the use of three recombinant viral proteins (recp40, recp23, and recp18). This assay system is more sensitive and rapid than the methods currently used for the serologic diagnosis of infection such as Western blotting (immunoblotting), indirect immunofluorescence test, or immunoprecipitation.
Oxygenation and spontaneous deamination of 2-aminobenzenesulphonic acid in Alcaligenes sp. strain O-1 with subsequent meta ring cleavage and spontaneous desulphonation to 2-hydroxymuconic acid (1994)

2-Aminobenzenesulphonic acid (2AS) is degraded by Alcaligenes sp. strain O-1 via a previously detected but unidentified intermediate. A mutant of strain O-1 was found to excrete this intermediate, which was isolated and identified by m.s., 1H- and 13C-n.m.r. as 3-sulphocatechol (3SC). Proteins from cell extracts of strain O-1 were separated by anion-exchange chromatography. A multicomponent oxygenase was observed to convert 1 mol each of NADH, O2 and 2AS into 1 mol each of 3SC, NH3 and NAD+. The enzyme presumably catalysed formation of the ring of a 2-amino-2,3-diol moiety, and elimination in the amino group led to a rearomatization. 3SC was further degraded via meta ring cleavage, which could be prevented by inactivation of the 3-sulphocatechol-2,3-dioxygenase (3SC23O) with 3-chlorocatechol. In Tris buffer, the separated 3SC23O catalysed the reaction of 1 mol each of 3SC and O2 involving a transient yellow intermediate, and release of 1 mol of sulphite and two organic products. The major product was identified by n.m.r. and by g.c./m.s. as 5-carboxypenta-2,4-dien-5-olide (CPDO), an indicator of formation of 2-hydroxymuconic acid (2HM). The second product was identified as the Z,E isomer of 2HM by comparison with authentic material. When the CPDO in the product mixture was chemically hydrolysed to (Z,E)-2HM, 1 mol of (Z,E)-2HM/mol of 3SC was observed. If oxygenation of 3SC by 3SC23O was carried out in phosphate buffer, only a single product was detected, a keto form of 2HM. This dioate was also formed from authentic (Z,E)-2HM in phosphate buffer. Formation of the natural product (Z,E)-2HM from the xenobiotic, 3SC, seems to involve oxygenation to the unstable 2-hydroxy-6-sulphonomuconic acid semialdehyde, which hydrolyses spontaneously to 2HM. There would appear to be at least one spontaneous reaction per enzyme reaction in this pathway.
Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study (2010)

Plasma galectin-3 is a novel prognostic marker in patients with chronic HF. Its prognostic value is independent of severity of HF, as assessed by NT-proBNP levels, and it may potentially be used in the management of such patients.
Excessive CpG 1668 stimulation triggers IL‐10 production by cDC that inhibits IFN‐α responses by pDC (2008)

Upon stimulation with a wide range of concentrations of CpG oligodeoxynucleotide 2216 (CpG 2216), plasmacytoid DC are induced to produce type I IFN (IFN-alpha/beta). In contrast, CpG 1668 shows a bell-shaped dose-response correlation, i.e. only intermediate but not high doses of CpG 1668 induce IFN-alpha/beta. Interestingly, high-dose CpG 1668 completely inhibited IFN-alpha responses induced by CpG 2216. Experiments using supernatant of high-dose CpG-1668-treated cells indicated that secreted inhibitor(s) mediated the IFN-alpha shut-off. Among modulating cytokines, IL-10 turned out to be one important negative regulator. In line with this, supernatants of IL-10-deficient DC cultures stimulated with high-dose CpG 1668 did not inhibit IFN-alpha production. Interestingly, high-dose CpG 1668 also inhibited IFN-alpha responses induced by the DNA-encoded mouse cytomegalovirus, whereas IFN-alpha responses induced by negative-strand RNA-encoded vesicular stomatitis virus were only marginally affected. Experiments with DC cultures devoid of TLR9 indicated that TLR9 was critically required to mediate stimulatory and modulatory signals by low and high concentrations of CpG 1668, respectively. Analysis of purified DC subsets showed that conventional DC were the main IL-10 producers, whereas plasmacytoid DC hardly produced any IL-10.
Gene Therapy in Inflammatory Diseases (2000)

List of Contributors. Preface. Christopher H. Evans, Paul D. Robbins: Gene therapy for inflammatory diseases - basic concepts. Sergei S. Makarov: Gene therapy for rheumatoid arthritis pre-clinical studies. Thomas Pap, Ulf Muller-Ladner, Klaus M. Hummel, Renate E. Gay and Steffen Gay: Cartilage erosion in rheumatoid arthritis studies in scid mouse model. Thomas S. Muzzonigro, Richard Kang, J. Reinecke, Peter Wehling, M.C. Wasko and James H. Herndon: Gene therapy for rheumatoid arthritis: clinical studies. Alistair J. Ramsay, Simon P. Hogan, Paul S. Foster and Yelin Xiong: Cytokine gene therapy of allergic airways inflammation. Philip C. Fox and Brian C. O'Connell: Gene therapy for inflammatory diseases of the salivary glands. Huang-Ge Zhang, Martin Fleck, Hui-Chen Hsu, Carl K. Edwards III, David T. Curiel, Tong Zhou and John D. Mountz: Gene therapy for management of lupus: correction of Fas and Fas ligand-induced apoptosis in murine disease - therapeutic rational and strategies. Michael K. Shaw, Richard DalCanto and C. Garrison Fathman: Gene therapy for Multiple Sclerosis. Nick Giannoukakis, Massimo Trucco and Paul D. Robbins: Gene therapy for type I Diabetes Mellitus. Jonathan S. Bromberg, Lisa A. DeBruyne, Randall S. Sung and Lihui Qin: Gene transfer to facilitate ransplantation. A. Paul Godillot, Michael Madaio, David B. Weiner and William V. Williams: DNA vaccination as an anti-inflammatory strategy. Masayuki Miyata, Yukio Sato and Reiji Kasukawa: Naked DNA as a gene delivery vehicle in inflammatory diseases. Steven C. Ghivizzani, Eric R. Lechman, Daniel Jaffurs, Zhibao Mi, Richard Kang, Thomas Muzzonigro, Christopher H. Evans and Paul D. Robbins: Animal models of arthritis generated by gene transfer.
Free-Induction-Decay Magnetometer Based on a Microfabricated Cs Vapor Cell (2018)

Microfabricated atomic magnetometers are important for fundamental research and numerous applications, including geophysical surveying and biological imaging, as they provide a sensitive, accurate, and portable alternative to standard magnetic sensing. The strong scalability and all-optical nature of the free-induction-decay (FID) magnetometer also benefit applications requiring sensor networks. This study shows the advantages of applying synchronous modulation and differential polarimetric detection in an FID setting, for measuring picotesla-level fields using a miniaturized Cs vapor cell.
Concomitant medication use in postmenopausal women using estrogen therapy (2001)

Greater use of certain prescription medications by estrogen users than by nonusers should be considered in studying the health effects of estrogen replacement therapy.
Recent Applications of Click Chemistry for the Synthesis of Radiotracers for Molecular Imaging (2009)

Click chemistry has received considerable attention as powerful modular synthesis approach, which has found numerous applications in many areas of modern organic chemistry, drug discovery and material science. Recently, click chemistry, and in particular the copper-mediated 1,3-dipolar [3+2] cycloaddition between azides and alkynes, has also entered the field of radiopharmaceutical sciences. This review addresses the recent developments of click chemistry for the synthesis of various radiotracers for molecular imaging purposes. Click chemistry-based radiotracers that will be covered include peptides and small organic molecules containing the short-lived positron emitter fluorine-18, and the gamma-emitters technetium-99m, indium-111, and iodine-125. Keywords: Click chemistry, radiopharmaceutical science, radiotracer
Structure determination of a Galectin‐3–carbohydrate complex using paramagnetism‐based NMR constraints (2008)

The determination of the location and conformation of a natural ligand bound to a protein receptor is often a first step in the rational design of molecules that can modulate receptor function. NMR observables, including NOEs, often provide the basis for these determinations. However, when ligands are carbohydrates, interactions mediated by extensive hydrogen-bonding networks often reduce or eliminate NOEs between ligand and protein protons. In these cases, it is useful to look to other distance- and orientation-dependent observables that can constrain the geometry of ligand-protein complexes. Here we illustrate the use of paramagnetism-based NMR constraints, including pseudo-contact shifts (PCS) and field-induced residual dipolar couplings (RDCs). When a paramagnetic center can be attached to the protein, field-induced RDCs and PCS reflect only bound-state properties of the ligand, even when averages over small fractions of bound states and large fractions of free states are observed. The effects can also be observed over a long range, making it possible to attach a paramagnetic center to a remote part of the protein. The system studied here is a Galectin-3-lactose complex. A lanthanide-binding peptide showing minimal flexibility with respect to the protein was integrated into the C terminus of an expression construct for the Galectin-3-carbohydrate-binding domain. Dysprosium ion, which has a large magnetic susceptibility anisotropy, was complexed to the peptide, making it possible to observe both PCSs and field-induced RDCs for the protein and the ligand. The structure determined from these constraints shows agreement with a crystal structure of a Galectin-3-N-acetyllactosamine complex.
Covalent immobilization of amino acids on the porous silicon surface (2010)

Abstract In this work, we report on a multi‐step route fully compatible with the mild conditions required for anchoring amino acids onto the porous silicon (PSi) surface. A dense monolayer of acid chains is first grafted via thermal hydrosilylation of undecylenic acid at the surface of hydrogenated PSi. The reaction takes place at the terminal CC double bond and yields an organic monolayer covalently attached to the surface through SiC bonds. Next, the acid terminal groups are transformed to succinimidyl ester terminations. This reaction, called activation, is achieved using N ‐hydroxysuccinimide (NHS) in the presence of the water‐soluble N ‐ethyl‐ N ′‐(3‐dimethylaminopropyl)carbodiimide (EDC). The surface, now bearing an ‘activated ester’ termination, is subsequently made to react with the amino end of the amino acid, allowing for its covalent attachment through the formation of an amide bond. The reaction efficiency at each stage of functionalization was confirmed using Fourier transform infrared (FT‐IR) measurements. SIMS depth profiling showed a significant level of carbon incorporation throughout the PSi layer. Electrochemical behavior of the amino‐acid‐modified PSi in the presence of copper ions was studied by means of cyclic voltammetry measurements. Copyright © 2010 John Wiley &amp; Sons, Ltd.
A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire (2012)

The isolation of circulating tumor cells (CTCs) from the blood of patients afflicted with solid malignant tumors becomes increasingly important as it may serve as a 'liquid biopsy' with the potential of monitoring the course of the cancer disease and its response to cancer therapy, with subsequent molecular characterization. For this purpose, we functionalized a structured medical Seldinger guidewire (FSMW), normally used to obtain safe access to blood vessels and other organ cavities, with a chimeric monoclonal antibody directed to the cell surface expressed epithelial cell surface adhesion molecule (EpCAM). This medical device was optimized in vitro and its biocompatibility was tested according to the regulations for medical devices and found to be safe with no noteworthy side effects. Suitability, specificity and sensitivity of the FSMW to catch and enrich CTCs in vivo from circulating peripheral blood were tested in 24 breast cancer or non-small cell lung cancer (NSCLC) patients and in 29 healthy volunteers. For this, the FSMW was inserted through a standard venous cannula into the cubital veins of healthy volunteers or cancer patients for the duration of 30 min. After removal, CTCs were identified by immuno-cytochemical staining of EpCAM and/or cytokeratins and staining of their nuclei and counted. The FSMW successfully enriched EpCAM-positive CTCs from 22 of the 24 patients, with a median of 5.5 (0-50) CTCs in breast cancer (n=12) and 16 (2-515) CTCs in NSCLC (n=12). CTCs could be isolated across all tumor stages, including early stage cancer, in which distant metastases were not yet diagnosed, while no CTCs could be detected in healthy volunteers. In this observatory study, no adverse effects were noted. Evidently, the FSMW has the potential to become an important device to enrich CTCs in vivo for monitoring the course of the cancer disease and the efficacy of anticancer treatment.