gebhart/patrepeval huggingface dataset:
Recent insights into androgen action on the anatomical and physiological substrate of penile erection (2006)

Erectile response is centrally and peripherally regulated by androgens. The original insights into the mechanisms of action of androgens were that androgens particularly exert effects on libido and that erections in response to erotic stimuli were relatively androgen-independent. It was shown that sexual functions in men required androgen levels at the low end of reference values of testosterone. So it seemed that testosterone was not useful treatment for men with erectile difficulties, particularly following the advent of the phosphodiesterase type 5 (PDE5) inhibitors. However, approximately 50% of those treated with PDE5 inhibitors discontinue their treatment. A number of recent developments shed new light on testosterone treatment of erectile dysfunction (ED) in aging men. (1) A recent insight is that, in contrast to younger men, elderly men might require higher levels of testosterone for normal sexual functioning. (2) Several studies have indicated that PDE5 inhibitors are not always sufficient to restore erectile potency in men, and that testosterone improves the therapeutical response to PDE5 inhibitors considerably. (3) There is growing insight that testosterone has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, reversible upon androgen replacement. The synthesis of PDE5 is upregulated by androgens, and the arterial inflow into the penis is improved by giving androgen. The above invites a re-examination of the merits of giving testosterone to aging men with ED. The beneficial effects of PDE5 inhibitors may only be optimally expressed in a eugonadal environment.
Improved performance of the second generation α1‐AGP columns: Applications to the routine assay of plasma levels of alfuzosin hydrochloride (1989)

Described is a direct enantioselective separation of the enantiomers of alfuzosin hydrochloride on the second generation alpha 1-AGP column which offers improved efficiency, shorter analysis, and improved stability with respect to the first generation columns. The method has been applied to the analysis of drug substance in rat plasma. This highly efficient extraction method and the use of fluorimetric detection result in selective and sensitive determination of the enantiomers. The analytical validation parameters demonstrate the applicability of this method to pharmacokinetic and metabolic studies.
Cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium (1987)

The enteric bacterium Salmonella typhimurium synthesizes cobalamin (vitamin B12) de novo only under anaerobic growth conditions. We initiated a genetic analysis of the cobalamin biosynthetic (cob) gene cluster, Stable cob::lac operon fusions were generated by insertions of a transposition-defective derivative of bacteriophage Mu d1 (Ap lac) into the cob genes. beta-Galactosidase synthesis was repressed in the presence of exogenously supplied cyanocobalamin, demonstrating that the cobalamin biosynthetic pathway was regulated by end-product repression. Transcriptional polarity studies showed that the cob genes responsible for synthesis of the corrinoid intermediate cobinamide (branch I of the pathway) were organized into a single operon. Genes for the synthesis of 5,6-dimethylbenzimidazole (branch II) and the final assembly of the complete cobalamin molecule (branch III) were organized into two or more additional operons. All of the known cob genes (in branches I, II, and III) were transcribed in a counterclockwise direction relative to the S. typhimurium genetic map. These genes are located at 41 map units and near the his operon. No essential genes lie between the his and cob operons. Mutants that carried deletions extending from the his genes into the cob region were isolated and characterized. By using these mutants, a deletion map of the branch I cob operon was constructed and the order of genes (his-cobI-cobIII-cobII) was inferred.
Homocysteine Upregulates Resistin Production From Adipocytes In Vivo and In Vitro (2008)

HHcy may promote insulin resistance through the induction of resistin expression and secretion from adipocytes via the activation of the ROS-PKC-NF-kappaB pathway.
Palladium Couplings on Metallocalix[4]arenes:  A Efficient Synthesis of New Functionalized Cavities (1998)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTPalladium Couplings on Metallocalix[4]arenes: A Efficient Synthesis of New Functionalized CavitiesBing Xu, Yi-Jun Miao, and Timothy M. SwagerView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: J. Org. Chem. 1998, 63, 23, 8561–8564Publication Date (Web):October 27, 1998Publication History Received12 May 1998Published online27 October 1998Published inissue 1 November 1998https://pubs.acs.org/doi/10.1021/jo980910nhttps://doi.org/10.1021/jo980910nbrief-reportACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views273Altmetric-Citations12LEARN 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 SUBJECTS:Aromatic compounds,Cavities,Functionalization,Supramolecular structures and assemblies,Tungsten Get e-Alerts
Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection (2016)

Tissue-resident memory T cells (TRM) are a recently defined, noncirculating subset with the potential for rapid in situ protective responses, although their generation and role in vaccine-mediated immune responses is unclear. Here, we assessed TRM generation and lung-localized protection following administration of currently licensed influenza vaccines, including injectable inactivated influenza virus (IIV, Fluzone) and i.n. administered live-attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially induced strain-specific neutralizing antibodies, LAIV generated lung-localized, virus-specific T cell responses. Moreover, LAIV but not IIV generated lung CD4<sup>+</sup> TRM and virus-specific CD8<sup>+</sup> TRM, similar in phenotype to those generated by influenza virus infection. Importantly, these vaccine-generated TRM mediated cross-strain protection, independent of circulating T cells and neutralizing antibodies, which persisted long-term after vaccination. Interestingly, intranasal administration of IIV or injection of LAIV failed to elicit T cell responses or provide protection against viral infection, demonstrating dual requirements for respiratory targeting and a live-attenuated strain to establish TRM. The ability of LAIV to generate lung TRM capable of providing long-term protection against nonvaccine viral strains, as demonstrated here, has important implications for protecting the population against emergent influenza pandemics by direct fortification of lung-specific immunity.
A unique cell surface antigen identifying lymphoid malignancies of B cell origin. (1981)

A monoclonal antibody (anti-B1) specific for a unique B cell surface differentiation antigen was used to characterize the malignant cells from patients with leukemias or lymphomas. All tumor cells from patients with lymphomas or chronic lymphocytic leukemias, bearing either monoclonal kappa lambda light chain, expressed the B1 antigen. In contrast, tumor cells from T cell leukemias and lymphomas or acute myeloblastic leukemia were unreactive. Approximately 50% of acute lymphoblastic leukemias (ALL) of non-T origin and 50% of chronic myelocytic leukemia in blast crisis were also anti-B1 reactive. moreover, 21 of 28 patients with the common ALL antigen (CALLA) positive form of ALL were anti-B1 positive, whereas 0 of 13 patients with CALLA negative ALL were reactive. These observations demonstrate that an antigen present on normal B cells is expressed on the vast majority of B cell lymphomas and on approximately 75% of CALLA positive ALL, suggesting that these tumors may share a common B cell lineage.
Ascending Auctions with Package Bidding (2002)

Turnkey institutional repository software featuring professional-grade publishing and faculty profiles tools to openly publish, manage and showcase the full spectrum of your institution’s research, scholarship and expertise
The natural history of the immune response to exogenous factor VIII in severe haemophilia A (1998)

The development of inhibitory antibodies to factor VIII (fVIII) in severe haemophilia A patients is a serious therapeutic complication. Using a highly sensitive immunoprecipitation (IP) assay which measures all anti-fVIII antibodies, we have tested severe haemophilic plasmas from two clinical studies. Inhibitor titres in the range of 0.4 to 1 Bethesda units/ml (BU/ml) could not be verified by IP as being due to an immune response to fVIII in 35% of plasmas tested. Low fVIII recoveries were likewise correlated with the presence of antibodies in 29% of plasmas tested. However, 16% of plasmas without inhibitor titres had immune responses as measured by IP. The rapidity of antibody appearance did not allow their effective detection by IP before development of inhibitor titres. These results suggest that the IP assay can provide a valuable confirmation of anti-fVIII antibody production when the Bethesda assay is low or negative and where clinical observations suggest their presence, but they cannot be used reliably to detect early immune responses.
Layer net: a new self-organizing network protocol (2002)

A protocol is proposed for the generation and operation of a self-organizing multihop radio network, which is capable of creating its own topology and transmission schedules dynamically and in a distributed manner. The protocol commences operation in a random-access mode of operation and then gradually switches over to a synchronous schedules mode of operation. The protocol was simulated up to the end of the scheduling phase. This included the generation of node positions, tree formation, addition of links and the scheduling of these links. The percentage increase in average hop distance between nodes in the generated network over the fully connected network (the network with all possible links between physical neighbors) was found to vary between 10% to 15%. Empirically, it appears that a schedule length that is twice the maximum degree is sufficient to allow the distributed generation of a conflict-free schedule.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Functional Wnt Signaling Is Increased in Idiopathic Pulmonary Fibrosis (2008)

Our study demonstrates that the Wnt/beta-catenin pathway is expressed and operative in adult lung epithelium. Increased Wnt/beta-catenin signaling may be involved in epithelial cell injury and hyperplasia, as well as impaired epithelial-mesenchymal cross-talk in IPF. Thus, modification of Wnt signaling may represent a therapeutic option in IPF.
The current state of two-dimensional electrophoresis with immobilized pH gradients (2000)

The original protocol of two-dimensional electrophoresis with immobilized pH gradient (IPG-Dalt; Görg et al., Electrophoresis 1988, 9, 531—546) is updated. Merits and limits of different methods for sample solubilization, sample application (by cup-loading or in-gel rehydration) with respect to the pH interval used for IPG-isoelectric focusing are critically discussed. Guidelines for running conditions of analytical and micropreparative IPG-Dalt, using wide IPGs up to pH 12 for overview patterns, or narrow IPGs for zoom-in gels for optimum resolution and detection of minor components, are stated. Results with extended separation distances as well as automated procedures are demonstrated, and a comparison between protein detection by silver staining and fluorescent dyes is given. A brief trouble shooting guide is also included.
Principles of adoptive T cell cancer therapy (2007)

The transfusion of T cells, also called adoptive T cell therapy, is an effective treatment for viral infections and has induced regression of cancer in early-stage clinical trials. However, recent advances in cellular immunology and tumor biology are guiding new approaches to adoptive T cell therapy. For example, use of engineered T cells is being tested as a strategy to improve the functions of effector and memory T cells, and manipulation of the host to overcome immunotoxic effects in the tumor microenvironment has led to promising results in early-stage clinical trials. Challenges that face the field and must be addressed before adoptive T cell therapy can be translated into routine clinical practice are discussed.
Catalytic C-H activation in early transition-metal dialkylamides and alkoxides (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCatalytic C-H activation in early transition-metal dialkylamides and alkoxidesWilliam A. Nugent, Derick W. Ovenall, and Steven J. HolmesCite this: Organometallics 1983, 2, 1, 161–162Publication Date (Print):January 1, 1983Publication History Published online1 May 2002Published inissue 1 January 1983https://pubs.acs.org/doi/10.1021/om00073a031https://doi.org/10.1021/om00073a031research-articleACS PublicationsRequest reuse permissionsArticle Views1491Altmetric-Citations190LEARN 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
Stress proteins may provide a link between the immune response to infection and autoimmunity (1989)

Stress proteins are frequently the target of humoral and cell-mediated immune responses to infection. These proteins belong to highly conserved gene families and there is substantial sequence homology between antigens produced by pathogenic organisms and the corresponding proteins from mammalian cells. Human T cells from sites of infectious and autoimmune lesions proliferate in response to stress proteins, and mapping of antigenic determinants on a mycobacterial stress protein shows that both species specific and highly conserved, 'self-like', regions of the molecule can take part in immune recognition. It is proposed that the lymphocyte population induced in response to stress proteins of pathogens during infection includes cells capable of autoimmune recognition of the corresponding self protein. Local accumulation of self stress proteins--in response to viral infection, for example--may subsequently provide a stimulus for proliferation of such autoreactive lymphocytes, thereby triggering a cycle of events which may contribute to the pathological damage associated with autoimmune disease.
Differential role of E-selectin and P-selectin in T lymphocyte migration to cutaneous inflammatory reactions induced by cytokines (2002)

E‐selectin and P‐selectin are thought to be important in the infiltration of T lymphocytes in inflammation, but their role in cytokine‐induced cutaneous inflammatory reactions has not been examined. A technique for quantifying labeled T lymphocyte migration to cytokine‐induced dermal inflammation in mice was developed. After i.v. injection, 51Cr‐labeled T lymphocytes migrated to lesions induced by IFN‐γ and tumor necrosis factor (TNF)‐α, and in even greater numbers to the combination of IFN‐γ + TNF‐α, and to sites injected with concanavalin A (Con A). In E‐selectin mAb‐treated and in E‐selectin‐deficient mice, IFN‐γ‐, IFN‐γ + TNF‐α‐ and Con A‐induced T cell accumulation was inhibited by 45–65%, but TNF‐α‐induced infiltration was unaffected. In P‐selectin mAb‐treated and P‐selectin‐deficient mice, T cell accumulation remained unchanged in most of the lesions. Combined, E‐selectin and P‐selectin mAb treatment inhibited T cell accumulation in all four types of reactions, and significantly more than E‐selectin blockade alone in migration to Con A. Results in E‐selectin‐ and P‐selectin‐deficient mice confirmed these observations, and demonstrated strain‐dependent differences in the contributions of the two selectins. In conclusion, T cells migrating to dermal inflammatory reactions utilize both E‐selectin and P‐selectin, but alternate adhesion pathways also contribute, since blocking both endothelial selectins does not abolish T cell migration. P‐selectin plays a less important role than E‐selectin, since blocking E‐selectin, but not P‐selectin, alone decreased T cell accumulation. The relative contribution of the selectins varies depending on the initiating inflammatory stimulus and the genetic background.
A Fully Integrated Monolithic Microchip Electrospray Device for Mass Spectrometry (2000)

A novel microfabricated nozzle has been developed for the electrospray of liquids from microfluidic devices for analysis by mass spectrometry. The electrospray device was fabricated from a monolithic silicon substrate using deep reactive ion etching and other standard semiconductor techniques to etch nozzles from the planar surface of a silicon wafer. A channel extends through the wafer from the tip of the nozzle to a reservoir etched into the opposite planar surface of the wafer. Nozzle diameters as small as 15 microm have been fabricated using this method. The microfabricated electrospray device provides a reproducible, controllable, and robust means of producing nano-electrospray of a liquid sample. The electrospray device was interfaced to an atmospheric pressure ionization time-of-flight mass spectrometer using continuous infusion of test compounds at low nanoliter-per-minute flow rates. Nozzle-to-nozzle signal intensity reproducibility using 10 nozzles was demonstrated to be 12% with single-nozzle signal stability routinely less than 4% relative standard deviation (RSD). Solvent compositions have been electrosprayed ranging from 100% organic to 100% aqueous. The signal-to-noise ratio from the infusion of a 10 nM cytochrome c solution in 100% water at 100 nL/min was 450:1. Microchip electrospray nozzles were compared with pulled capillaries for overall sensitivity and signal stability for small and large molecules. The microchip electrospray nozzles showed a 1.5-3-times increase in sensitivity compared with that from a pulled capillary, and signal stability with the microchip was 2-4% RSD compared with 4-10% with a pulled capillary. Electrospray device lifetimes achieved thus far have exceeded 8 h of continuous operation and should be sufficient for typical microfluidic applications. The total volume of the electrospray device is less than 25 pL, making it suitable for combination with microfluidic separation devices.
Autophagy Controls IL-1β Secretion by Targeting Pro-IL-1β for Degradation (2011)

Autophagy is a key regulator of cellular homeostasis that can be activated by pathogen-associated molecules and recently has been shown to influence IL-1β secretion by macrophages. However, the mechanisms behind this are unclear. Here, we describe a novel role for autophagy in regulating the production of IL-1β in antigen-presenting cells. After treatment of macrophages with Toll-like receptor ligands, pro-IL-1β was specifically sequestered into autophagosomes, whereas further activation of autophagy with rapamycin induced the degradation of pro-IL-1β and blocked secretion of the mature cytokine. Inhibition of autophagy promoted the processing and secretion of IL-1β by antigen-presenting cells in an NLRP3- and TRIF-dependent manner. This effect was reduced by inhibition of reactive oxygen species but was independent of NOX2. Induction of autophagy in mice in vivo with rapamycin reduced serum levels of IL-1β in response to challenge with LPS. These data demonstrate that autophagy controls the production of IL-1β through at least two separate mechanisms: by targeting pro-IL-1β for lysosomal degradation and by regulating activation of the NLRP3 inflammasome.
Blockade of Striatal Adenosine A2AReceptor Reduces, through a Presynaptic Mechanism, Quinolinic Acid-Induced Excitotoxicity: Possible Relevance to Neuroprotective Interventions in Neurodegenerative Diseases of the Striatum (2002)

The aim of the present study was to evaluate whether, and by means of which mechanisms, the adenosine A2A receptor antagonist SCH 58261 [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine] exerted neuroprotective effects in a rat model of Huntington's disease. In a first set of experiments, SCH 58261 (0.01 and 1 mg/kg) was administered intraperitoneally to Wistar rats 20 min before the bilateral striatal injection of quinolinic acid (QA) (300 nmol/1 microl). SCH 58261 (0.01 but not 1 mg/kg, i.p.) did reduce significantly the effects of QA on motor activity, electroencephalographic changes, and striatal gliosis. Because QA acts by both increasing glutamate outflow and directly stimulating NMDA receptors, a second set of experiments was performed to evaluate whether SCH 58261 acted by preventing the presynaptic and/or the postsynaptic effects of QA. In microdialysis experiments in naive rats, striatal perfusion with QA (5 mm) enhanced glutamate levels by approximately 500%. Such an effect of QA was completely antagonized by pretreatment with SCH 58261 (0.01 but not 1 mg/kg, i.p.). In primary striatal cultures, bath application of QA (900 microm) significantly increased intracellular calcium levels, an effect prevented by the NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate]. In this model, bath application of SCH 58261 (15-200 nm) tended to potentiate QA-induced calcium increase. We conclude the following: (1) the adenosine A2A receptor antagonist SCH 58261 has neuroprotective effects, although only at low doses, in an excitotoxic rat model of HD, and (2) the inhibition of QA-evoked glutamate outflow seems to be the major mechanism underlying the neuroprotective effects of SCH 58261.