gebhart/patrepeval huggingface dataset:
Selective PRMT5 Inhibitors Suppress Human CD8+ T Cells by Upregulation of p53 and Impairment of the AKT Pathway Similar to the Tumor Metabolite MTA (2019)

Genetic alterations in tumor cells provide promising targets for antitumor therapy. Recently, loss of methylthioadenosine phosphorylase (MTAP), a deletion frequently occurring in cancer, has been shown to create vulnerability to the inhibition of the protein arginine methyltransferase 5 (PRMT5). MTAP deficiency leads to accumulation of methylthioadenosine (MTA), which reduces PRMT5 activity, and thus, sensitizes the tumor cells to selective PRMT5 inhibitors (PRMT5i). PRMT5i are investigated as a new strategy to selectively kill MTAP-deficient tumor cells by blocking residual PRMT5 activity, but also to treat PRMT5-overexpressing tumors. Although many studies investigated the role of PRMT5 in cancer, only little data exist about the effect of PRMT5 inhibition on immune cells. As we could show that the tumor metabolite MTA suppresses T cells, we asked whether selective PRMT5 inhibition is detrimental for T-cell immune responses. Therefore, we examined the effect of the synthetic PRMT5 inhibitor EPZ015666 on human CD8<sup>+</sup> T cells in direct comparison with the naturally occurring PRMT5-inhibiting molecule MTA. Both compounds reduced T-cell proliferation, viability, and functionality. In addition, T-cell metabolism was impaired upon PRMT5 inhibition. These effects coincided with the induction of p53 expression and reduced AKT/mTOR signaling. Our data clearly demonstrate that PRMT5 activity is involved in various cellular processes of human CD8<sup>+</sup> T cells associated with essential T-cell functions. Therefore, not only tumor cells, but also antitumor immune responses, are compromised by PRMT5 inhibitors. This emphasizes the importance of considering side effects on the immune system when developing new strategies to specifically target not only MTAP-deficient tumors.
Photoaffinity labeling of benzodiazepine receptors causes altered agonist-antagonist interactions (1983)

Previous studies have shown that [3H]flunitrazepam forms irreversible cross-links with brain tissue when exposed to ultraviolet irradiation. Comparison of the amount of [3H]flunitrazepam irreversibly incorporated and the number of benzodiazepine binding sites blocked after photolabeling has indicated that several binding sites are inactivated for each molecule of [3H]flunitrazepam incorporated. To learn the cause of this discrepancy, binding to the benzodiazepine binding sites has been examined using several radiolabeled benzodiazepine antagonists. Binding of a beta-carboline ester, CGS-8216, and Ro 15-1788 was not altered by photolabeling; however, displacement studies revealed that photolabeling converted a homogeneous set of benzodiazepine binding sites into two subsets: one of high affinity (unaltered sites) and one of low affinity. The low affinity sites could be detected by displacement studies of antagonist binding by benzodiazepines, and conversion to a low affinity form accounts for the discrepancy observed after photolabeling using [3H]flunitrazepam as ligand.
Development and validation of an ultra‐fast and sensitive microflow liquid chromatography‐tandem mass spectrometry (MFLC‐MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans (2016)

Lysergic acid diethylamide (LSD) is a semi-synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso-LSD, 2-oxo 3-hydroxy-LSD (oxo-HO-LSD), and N-desmethyl-LSD (nor-LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)-national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso-LSD, and oxo-HO-LSD in all participants. Additionally, hydroxy-LSD (HO-LSD) and HO-LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor-LSD was only sporadically detected. Elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd.
Cyclooligomeric receptors for the sequence selective binding of peptides. A tetrahedral receptor from trimesic acid and 1,2-diamines (1994)

The first members of a new family of tetrahedral receptors (2) have been prepared from trimesic acid and certain chiral 1,2-diamines. A survey of the binding properties of one of these with a 50,000-member peptide library finds high selectivity for N-acetylated terminal residues (particularly Ac-(D)Gln) and the dipeptide sequence (L)Gln-(L)Pro.
Protection of sheep against caseous lymphadenitis by use of a single oral dose of live recombinant Corynebacterium pseudotuberculosis (1994)

An inactive form of the Corynebacterium pseudotuberculosis phospholipase D (PLD) gene was constructed and expressed in a PLD-negative strain (designated Toxminus) of C. pseudotuberculosis. Antibody responses specific to Toxminus and both Toxminus and PLD proteins were detected in sheep following oral administration of Toxminus or Toxminus expressing the PLD toxoid, respectively. However, only those sheep vaccinated with Toxminus expressing PLD toxoid were protected against wild-type challenge. These results confirm the importance of PLD as a protective antigen and demonstrate both the potential for developing an oral caseous lymphadenitis vaccine and C. pseudotuberculosis Toxminus as a live vaccine vector.
Multifunctional role of dextran sulfate sodium for in vivo modeling of intestinal diseases (2012)

We showed that using a murine DSS-induced experimental colitis model system, and presenting data in a longitudinal manner on a per mouse basis, enhanced the usefulness of this model, and provided novel insights into the role of an innate immune receptor in intestinal repair. By elucidating the mechanistic basis of intestinal injury and repair, we can begin to understand the etiology of IBDs, enabling development of novel therapeutics or prophylactics.
Novel copper complexes of chiral diphosphines: preparation, structure, and use to form rhodium complex catalysts for chiral hydrogenations (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel copper complexes of chiral diphosphines: preparation, structure, and use to form rhodium complex catalysts for chiral hydrogenationsJohn M. Townsend, John F. Blount, Ruen Chu Sun, Sonja Zawoiski, and Donald Valentine Jr.Cite this: J. Org. Chem. 1980, 45, 15, 2995–2999Publication Date (Print):July 1, 1980Publication History Published online1 May 2002Published inissue 1 July 1980https://pubs.acs.org/doi/10.1021/jo01303a016https://doi.org/10.1021/jo01303a016research-articleACS PublicationsRequest reuse permissionsArticle Views558Altmetric-Citations36LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Echocardiographic measurements in normal subjects from infancy to old age. (1980)

Echocardiographic data from 92 younger normal subjects (1 month to 23 years of age) and 136 older normal subjects (20-97 years of age) were pooled and analyzed to obtain prediction equations for normal echocardiographic values. Using a bivariate regression model with the assumption that variability is constant as a percentage of the expected value, we developed regression equation and graphs that allow calculation of a 95% prediction interval for several echocardiographic measurements as a function of the subject's age and either body weight or body surface area. Body weight could be substituted for body surface area with no loss of precision. Further, examination of residuals showed that the linear prediction model fit well for all ages and all echocardiographic measurements studied. The measurements were obtained using the recently published standards recommended by the American Society of Echocardiography.
Lentivirus induced arthritis in animals. (1992)

Retroviral arthritis in sheep and goats depends on persistent infection in the animals. Virus is latent in macrophage precursor cells and viral replication is initiated when these cells are induced to differentiate. Antiviral antibodies and cytokines modulate the efficiency of viral gene product expression. Specific cytokines induced during replication of the lentivirus in mononuclear cells are also responsible for directing infected cells from peripheral blood through the vascular endothelium to particular tissues. Cytokines induced by other infectious agents such as bacteria, mycoplasma or protozoa, may also contribute to this chemotactic process. Once in the tissue, macrophages interact with lymphocytes to induce an inflammatory cascade with further production of cytokines which enhances expression of class II major histocompatibility complex antigens and proliferation of B and CD8 lymphocytes. In addition, immune complexes between viral glycoproteins and immunoglobulins are produced locally and probably lead to further enhancement of pathological changes in the tissues.
Toward a clinically feasible gene expression-based subclassification strategy for septic shock: Proof of concept (2010)

We have provided initial evidence (proof of concept) for a clinically feasible and robust stratification strategy for pediatric septic shock based on a 100-gene signature and gene expression mosaics.
Computing Maximum-Likelihood Parameter Estimates of the Generalized Gamma Distribution by Numerical Root Isolation (1987)

The generalized gamma distribution (GGD) is important in reliability modeling and includes as special cases the Weibull, Gamma, and exponential distributions. Unfortunately, the numerical difficulties associated with fitting the GGD to data have been a major impediment to its wider use. The parameter likelihood equations (LEs) can possess no solution or several solutions, and the Newton-Raphson method is, in general, poorly behaved when applied to the LEs. This paper describes an algorithm which uses a heuristic root isolation method to circumvent these difficulties. The algorithm can be used to determine the maximum likelihood estimates of the parameters of the GGD or to indicate that none exists.
Organocopper chemistry. Halo-, cyano-, and carbonyl-substituted ketones from the corresponding acyl chlorides and organocopper reagents (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganocopper chemistry. Halo-, cyano-, and carbonyl-substituted ketones from the corresponding acyl chlorides and organocopper reagentsGary H. Posner, Charles E. Whitten, and Paul McFarlandCite this: J. Am. Chem. Soc. 1972, 94, 14, 5106–5108Publication Date (Print):July 1, 1972Publication History Published online1 May 2002Published inissue 1 July 1972https://pubs.acs.org/doi/10.1021/ja00769a066https://doi.org/10.1021/ja00769a066research-articleACS PublicationsRequest reuse permissionsArticle Views729Altmetric-Citations111LEARN 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
Identification of the Escherichia coli K‐12 Nramp orthologue (MntH) as a selective divalent metal ion transporter (2000)

The Escherichia coli mntH (formerly yfeP) gene encodes a putative membrane protein (MntH) highly similar to members of the eukaryotic Nramp family of divalent metal ion transporters. To determine the function of E. coli MntH, a null mutant was created and MntH was overexpressed both in wild-type E. coli and in the metal-dependent mutant hflB1(Ts). At the restrictive temperature 42 degrees C, the mntH null mutation reduces the suppression of hflB1(Ts) thermosensitivity by exogenous divalent metals. Conversely, overexpression of MntH restores growth at 42 degrees C, increases suppression of the ts phenotype by Fe(II) and Ni(II) and renders hflB1(Ts) cells hypersensitive to Mn(II). Transport studies in intact cells show that MntH selectively facilitates uptake of 54Mn(II) and 55Fe(II) in a temperature-, time- and proton-dependent manner. Competition studies in uptake assays and growth inhibition experiments in hflB1(Ts) mutants together indicate that MntH is a divalent metal cation transporter of broad substrate specificity. The functional characteristics of MntH suggest that it corresponds to the previously described manganese transporter of E. coli. This study indicates that proton-dependent divalent metal ion uptake has been preserved in the Nramp family from bacteria to humans.
Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly. (1992)

In the endoplasmic reticulum (ER), newly synthesized subunits of the T-cell antigen receptor (TCR), membrane-bound immunoglobulin (mIg), and major histocompatibility complex (MHC) class I antigens must fold correctly and assemble completely into multimeric protein complexes prior to transport to the cell surface. Although folding and assembly may occur spontaneously, the concept that molecular chaperones facilitate these events is emerging. Here, an intracellular protein of 90-kDa apparent molecular mass, denoted IP90, was shown to be an ER resident protein that associated with partial complexes of the TCR, mIg, and MHC class I proteins but was absent from fully assembled complexes. We speculate that IP90 might participate in folding and assembly processes of these and other multisubunit protein complexes during their transit through the ER.
Preparation of π-conjugated poly(thiophene-2,5-diyl), poly(p-phenylene), and related polymers using zerovalent nickel complexes. Linear structure and properties of the π-conjugated polymers (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of π-conjugated poly(thiophene-2,5-diyl), poly(p-phenylene), and related polymers using zerovalent nickel complexes. Linear structure and properties of the π-conjugated polymersTakakazu Yamamoto, Atsushi Morita, Yuichi Miyazaki, Tsukasa Maruyama, Hiroshi Wakayama, Zhen Hua Zhou, Yoshiyuki Nakamura, Takaki Kanbara, Shintaro Sasaki, and Kenji KubotaCite this: Macromolecules 1992, 25, 4, 1214–1223Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ma00030a003https://doi.org/10.1021/ma00030a003research-articleACS PublicationsRequest reuse permissionsArticle Views4282Altmetric-Citations405LEARN 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
Therapy of relapsed leukemia after allogeneic hematopoietic cell transplantation with T cells specific for minor histocompatibility antigens (2010)

The adoptive transfer of donor T cells that recognize recipient minor histocompatibility antigens (mHAgs) is a potential strategy for preventing or treating leukemic relapse after allogeneic hematopoietic cell transplantation (HCT). A total of 7 patients with recurrent leukemia after major histocompatibility complex (MHC)-matched allogeneic HCT were treated with infusions of donor-derived, ex vivo-expanded CD8(+) cytotoxic T lymphocyte (CTL) clones specific for tissue-restricted recipient mHAgs. The safety of T-cell therapy, in vivo persistence of transferred CTLs, and disease response were assessed. Molecular characterization of the mHAgs recognized by CTL clones administered to 3 patients was performed to provide insight into the antileukemic activity and safety of T-cell therapy. Pulmonary toxicity of CTL infusion was seen in 3 patients, was severe in 1 patient, and correlated with the level of expression of the mHAg-encoding genes in lung tissue. Adoptively transferred CTLs persisted in the blood up to 21 days after infusion, and 5 patients achieved complete but transient remissions after therapy. The results of these studies illustrate the potential to selectively enhance graft-versus-leukemia activity by the adoptive transfer of mHAg-specific T-cell clones and the challenges for the broad application of this approach in allogeneic HCT. This study has been registered at http://clinicaltrials.gov as NCT00107354.
Low-Power Low-Voltage Digital System for Wireless Heart Rate Monitoring Application (2007)

Low-power low-voltage digital system for wireless heart rate monitoring application is presented in this paper. This paper includes the system design and focuses more on the heart rate computing algorithm, digital baseband and the system design from FPGA prototyping to custom IC. The heart rate sensor system consists of an amplifier, an ADC (analog-to-digital converter), and a digital system. The digital system consists of a power/clock management block, a heart rate computing block and a digital baseband block. This system is implemented using discrete components and also in an integrated IC using 0.18-mum CMOS technology.
Percutaneous Tibial Nerve Stimulation Improves Female Sexual Function in Women With Overactive Bladder Syndrome (2016)

Percutaneous tibial nerve stimulation (PTNS) is an established treatment for overactive bladder (OAB), especially in women with other concomitant pelvic disorders, such as sexual impairment.
Electrospinning of Nanofiber Fibrinogen Structures (2002)

The first results of electrospinning fibrinogen nanofibers for use as a tissue-engineering scaffold, wound dressing, or hemostatic bandage are reported. Structures composed of fibrinogen fibers with an average diameter of 80−700 nm were electrospun from solutions composed of human or bovine fibrinogen fraction I dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol and minimal essential medium (Earle's salts). In summary, the electrospinning process is a simple and efficient technique for the fabrication of 3D structures composed of fibrinogen fibers, as would be present in the physiologic environment.
Field Applications of Capacitance-Resistive Models in Waterfloods (2008)

Abstract Application of fast, simple and yet powerful analytic tools, capacitance-resistive models (CRMs), are demonstrated with four field examples. Most waterfloods lend themselves to this treatment. This spreadsheet-based tool is ideally suited for engineers who manage daily flood performance. We envision CRM's application to precede any detailed full-field numerical modeling. We have selected field case studies in a way to demonstrate CRMs capabilities in different settings: a tank representation of a field, its ability to determine connectivity between the producers and injectors, and understanding flood efficiencies for the entire or a portion of a field. Significant insights about the flood performance over a short period can be gained by estimating fractions of injected fluid being directed from an injector to various producers and the time taken for an injection signal to reach a producer. Injector-to-producer connectivity may be inferred directly during the course of error minimization. Because the method circumvents geologic modeling and saturation matching, it lends itself to frequent usage without intervention of expert modelers.
Fast Feature Pyramids for Object Detection (2014)

Multi-resolution image features may be approximated via extrapolation from nearby scales, rather than being computed explicitly. This fundamental insight allows us to design object detection algorithms that are as accurate, and considerably faster, than the state-of-the-art. The computational bottleneck of many modern detectors is the computation of features at every scale of a finely-sampled image pyramid. Our key insight is that one may compute finely sampled feature pyramids at a fraction of the cost, without sacrificing performance: for a broad family of features we find that features computed at octave-spaced scale intervals are sufficient to approximate features on a finely-sampled pyramid. Extrapolation is inexpensive as compared to direct feature computation. As a result, our approximation yields considerable speedups with negligible loss in detection accuracy. We modify three diverse visual recognition systems to use fast feature pyramids and show results on both pedestrian detection (measured on the Caltech, INRIA, TUD-Brussels and ETH data sets) and general object detection (measured on the PASCAL VOC). The approach is general and is widely applicable to vision algorithms requiring fine-grained multi-scale analysis. Our approximation is valid for images with broad spectra (most natural images) and fails for images with narrow band-pass spectra (e.g., periodic textures).