gebhart/patrepeval huggingface dataset:
Parasympathetic control of the heart. II. A novel interganglionic intrinsic cardiac circuit mediates neural control of heart rate (2004)

Intracardiac pathways mediating the parasympathetic control of various cardiac functions are incompletely understood. Several intracardiac ganglia have been demonstrated to potently influence cardiac rate [the sinoatrial (SA) ganglion], atrioventricular (AV) conduction (the AV ganglion), or left ventricular contractility (the cranioventricular ganglion). However, there are numerous ganglia found throughout the heart whose functions are poorly characterized. One such ganglion, the posterior atrial (PA) ganglion, is found in a fat pad on the rostral dorsal surface of the right atrium. We have investigated the potential impact of this ganglion on cardiac rate and AV conduction. We report that microinjections of a ganglionic blocker into the PA ganglion significantly attenuates the negative chronotropic effects of vagal stimulation without significantly influencing negative dromotropic effects. Because prior evidence indicates that the PA ganglion does not project to the SA node, we neuroanatomically tested the hypothesis that the PA ganglion mediates its effect on cardiac rate through an interganglionic projection to the SA ganglion. Subsequent to microinjections of the retrograde tracer fast blue into the SA ganglion, >70% of the retrogradely labeled neurons found within five intracardiac ganglia throughout the heart were observed in the PA ganglion. The neuroanatomic data further indicate that intraganglionic neuronal circuits are found within the SA ganglion. The present data support the hypothesis that two interacting cardiac centers, i.e., the SA and PA ganglia, mediate the peripheral parasympathetic control of cardiac rate. These data further support the emerging concept of an intrinsic cardiac nervous system.
SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes (2017)

SLAMF7 is under intense investigation as a target for immunotherapy in multiple myeloma. In this study, we redirected the specificity of T cells to SLAMF7 through expression of a chimeric antigen receptor (CAR) derived from the huLuc63 antibody (elotuzumab) and demonstrate that SLAMF7-CAR T cells prepared from patients and healthy donors confer potent antimyeloma reactivity. We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received previous treatment with proteasome inhibitors and immunomodulatory drugs. Consequently, SLAMF7-CAR T cells conferred rapid cytolysis of previously untreated and R/R primary myeloma cells in vitro. In addition, a single administration of SLAMF7-CAR T cells led to resolution of medullary and extramedullary myeloma manifestations in a murine xenograft model in vivo. SLAMF7 is expressed on a fraction of normal lymphocytes, including subsets of natural killer (NK) cells, T cells, and B cells. After modification with the SLAMF7-CAR, both CD8<sup>+</sup> and CD4<sup>+</sup> T cells rapidly acquired and maintained a SLAMF7<sup>-</sup> phenotype and could be readily expanded to therapeutically relevant cell doses. We analyzed the recognition of normal lymphocytes by SLAMF7-CAR T cells and show that they induce selective fratricide of SLAMF7<sup>+/high</sup> NK cells, CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and B cells. Importantly, however, the fratricide conferred by SLAMF7-CAR T cells spares the SLAMF7<sup>-/low</sup> fraction in each cell subset and preserves functional lymphocytes, including virus-specific T cells. In aggregate, our data illustrate the potential use of SLAMF7-CAR T-cell therapy as an effective treatment against multiple myeloma and provide novel insights into the consequences of targeting SLAMF7 for the normal lymphocyte compartment.
Isolation and structural characterization of the Leishmania donovani kinetoplastid membrane protein-11, a major immunoreactive membrane glycoprotein (1995)

A novel membrane molecule, previously observed to be co-isolated with lipophosphoglycan and called lipophosphoglycan-associated protein, has been detected in Leishmania donovani promastigotes and amastigotes. This kinetoplastid membrane protein (KMP-11) has been purified by preparative SDS/PAGE after organic solvent extraction of promastigote membranes. Isoelectric-focusing experiments indicated that this was an acidic protein with an isoelectric point of 4.8. Immunoblot analysis of subcellular fractions, together with 125I-labelling experiments, showed this molecule to be associated with the promastigote cell surface membrane. KMP-11 was expressed at a copy number similar to that of lipophosphoglycan (1 x 10(6)-2 x 10(6) molecules per cell), making this glycoprotein one of the major features on the parasite cell surface. The primary structure, less a blocked N-terminal region, was determined by automated Edman degradation of peptides derived from CNBr or enzymic fragmentation. Several post-translational modifications were also found during these studies, including an O-linked oligosaccharide and an NG-monomethylarginine functionality which was verified by m.s. Finally, a set of sequential synthetic peptides was made based on the established partial sequence allowing structural determination of two distinct antibody-binding sites for the monoclonal antibodies L98 and L157.
Magnetic Source Imaging (1993)

Magnetic source imaging (MSI) is a new, noninvasive technique for defining the relationship between brain function and structure on a patient-to-patient basis. It achieves this by combining detailed neurophysiological data derived from magnetoencephalography with high-quality neuroanatomical data derived via magnetic resonance imaging. By the use of mathematical models, the spatial locations of those neurons that generate neuromagnetic signals of interest are estimated and subsequently marked on spatially aligned magnetic resonance images. There are three prominent types of clinical MSI examinations. These are: 1) functional mapping examinations in which sensory and motor functions are localized; 2) examinations of interictal epileptiform activity; and 3) examinations of abnormal low-frequency magnetic activity, which has been found to be present in a wide range of pathophysiological conditions. Functional mapping provides useful information regarding the relationship between the cortical representation of eloquent function and the location of pathological lesions that may be surgically resectable. This application is of particular utility in cases of intracortical masses that distort and obscure the local neuroanatomy. By defining the primary sites of interictal epileptiform activity, MSI examinations are useful in the surgical planning for the implantation of depth electrodes and the planning of partial lobectomies. Abnormal low-frequency magnetic activity appears to be a neurophysiological correlate of ischemic penumbra associated with stroke, neoplasms, and vascular malformations. Abnormal low-frequency magnetic activity has also been found to be present in several other conditions, including head trauma and psychiatric dysfunction, although the exact pathophysiological mechanisms are presently unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased 1,25-(OH)2D2 Concentration in a Patient with Malignancy-Associated Hypercalcemia Receiving Intravenous Hyperalimentation Inadvertently Supplemented with Vitamin D2. (1993)

A 55-year-old patient with hypercalcemic crisis due to gastric carcinoma with bone marrow metastasis was treated with bisphosphonate (pamidronate) and calcitonin. Urinary excretion of parathyroid hormone-related protein (PTHrP) was increased. When normocalcemia had been attained, intravenous hyperalimentation was started, in which 1,000 U vitamin D2 was inadvertently supplemented on days 5-18, On days 15-18, hypercalcemia rapidly recurred, accompanied by markedly increased serum levels of 25-OHD2 (9.1 ng/dl) and 1,25-(OH)2D2 (161 pg/ml). This clinical course suggests that PTHrP, like PTH, stimulated 1 alpha-hydroxylase activity and produced excessive 1,25-(OH)2D2. Vitamin D should not be administered to patients with malignancy-associated hypercalcemia, particularly that due to PTHrP-producing tumors.
Hybrid control and learning with coresets for autonomous vehicles (2017)

Modern autonomous systems such as driverless vehicles need to safely operate in a wide range of conditions. A potential solution is to employ a hybrid systems approach, where safety is guaranteed in each individual mode within the system. This offsets complexity and responsibility from the individual controllers onto the complexity of determining discrete mode transitions. In this work we propose an efficient framework based on recursive neural networks and coreset data summarization to learn the transitions between an arbitrary number of controller modes that can have arbitrary complexity. Our approach allows us to efficiently gather annotation data from the large-scale datasets that are required to train such hybrid nonlinear systems to be safe under all operating conditions, favoring underexplored parts of the data. We demonstrate the construction of the embedding, and efficient detection of switching points for autonomous and non-autonomous car data. We further show how our approach enables efficient sampling of training data, to further improve either our embedding or the controllers.
Solving the Multiple Competitive Facilities Location and Design Problem on the Plane (2009)

A continuous location problem in which a firm wants to set up two or more new facilities in a competitive environment is considered. Other facilities offering the same product or service already exist in the area. Both the locations and the qualities of the new facilities are to be found so as to maximize the profit obtained by the firm. This is a global optimization problem, with many local optima. In this paper we analyze several approaches to solve it, namely, three multistart local search heuristics, a multistart simulated annealing algorithm, and two variants of an evolutionary algorithm. Through a comprehensive computational study it is shown that the evolutionary algorithms are the heuristics that provide the best solutions. Furthermore, using a set of problems for which the optimal solutions are known, only the evolutionary algorithms were able to find the optimal solutions for all the instances. The evolutionary strategies presented in this paper can be easily adapted to handle other continuous location problems.
Fracturing Fluids (2013)

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IL-23 plays a key role in Helicobacter hepaticus –induced T cell–dependent colitis (2006)

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is caused in part by a dysregulated immune response to the intestinal flora. The common interleukin (IL)-12/IL-23p40 subunit is thought to be critical for the pathogenesis of IBD. We have analyzed the role of IL-12 versus IL-23 in two models of Helicobacter hepaticus-triggered T cell-dependent colitis, one involving anti-IL-10R monoclonal antibody treatment of infected T cell-sufficient hosts, and the other involving CD4+ T cell transfer into infected Rag-/- recipients. Our data demonstrate that IL-23 and not IL-12 is essential for the development of maximal intestinal disease. Although IL-23 has been implicated in the differentiation of IL-17-producing CD4+ T cells that alone are sufficient to induce autoimmune tissue reactivity, our results instead support a model in which IL-23 drives both interferon gamma and IL-17 responses that together synergize to trigger severe intestinal inflammation.
A generic scheme for color image retrieval based on the multivariate Wald-Wolfowitz test (2005)

In this study, a conceptually simple, yet flexible and extendable strategy to contrast two different color images is introduced. The proposed approach is based on the multivariate Wald-Wolfowitz test, a nonparametric test that assesses the commonality between two different sets of multivariate observations. It provides an aggregate gauge of the match between color images, taking into consideration all the (selected) low-level characteristics, while alleviating correspondence issues. We show that a powerful measure of similarity between two color images can emerge from the statistical comparison of their representations in a properly formed feature space. For the sake of simplicity, the RGB-space is selected as the feature space, while we are experimenting with different ways to represent the images within this space. By altering the feature-extraction implementation, complementary ways to portray the image content appear. The reported results, from the application on a diverse collection of images, clearly demonstrate the effectiveness of our method, its superiority over previous methods, and suggest that even further improvements can be achieved along the same line of research. It is not only the unifying character that makes our strategy appealing, but also the fact that the retrieval performance does not increase continuously with the amount of details in the image representation. The latter sets an upper limit to the computational demands and reminds of performance plateaus reached by novel approaches in information retrieval.
Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk (2008)

To determine whether inhibition of Syk would be useful in FcgammaR-dependent cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk function, in treating cytopenia. Both disease models responded favorably to treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP. Sixteen adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily. Doses were increased until a persistent response was seen, toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved persistent responses with platelet counts greater than 50 x 10(9)/L (50 000 mm(3)) on more than 67% (actually 95%) of their study visits, including 3 who had not persistently responded to thrombopoietic agents. Four others had nonsustained responses. Mean peak platelet count exceeded 100 x 10(9)/L (100 000 mm(3)) in these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342).
Pentaerythritol Derivatives. V.1 Preparation of Diethers of Pentaerythritol by Reduction of Acetals and Ketals2 (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPentaerythritol Derivatives. V.1 Preparation of Diethers of Pentaerythritol by Reduction of Acetals and Ketals2ABDUL-RAHMAN ABDUN-NUR and COSTAS H. ISSIDORIDESCite this: J. Org. Chem. 1962, 27, 1, 67–70Publication Date (Print):January 1, 1962Publication History Published online1 May 2002Published inissue 1 January 1962https://pubs.acs.org/doi/10.1021/jo01048a017https://doi.org/10.1021/jo01048a017research-articleACS PublicationsRequest reuse permissionsArticle Views556Altmetric-Citations29LEARN 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
Blockmania: from Block DAGs to Consensus (2018)

Blockmania is a byzantine consensus protocol. Nodes emit blocks forming a directed acyclic graph (block DAG) that is subsequently interpreted by each node separately to ensure consensus with safety, liveness and finality. The resulting system has communication complexity $O(N^2)$ even in the worse case, and very low constant factors --- as compared to $O(N^4)$ for PBFT; it is leaderless; and network operations do not depend on the composition of the quorum or node stake. This makes Blockmania very efficient (leading to over 400K transactions per second on a wide area network), and ideal for dynamic membership and flexible and non-interrupted proof-of-stake protocols. A X-Blockmania variant, has $O(N)$ communication cost but also higher latency $O(\log N)$.
Active-specific immunotherapy for melanoma. (1990)

Twenty-five patients with metastatic melanoma were treated with a therapeutic vaccine ("theraccine") consisting of allogeneic melanoma lysates and a novel adjuvant, DETOX (Ribi ImmunoChem Research, Inc, Hamilton, MT). Each patient received 200 antigenic units (20 x 10(6) tumor cell equivalents) subcutaneously on weeks 1, 2, 3, 4, and 6. Clinical responses included one complete remission, three partial remissions, and a long-term (17-month) stability. Two other patients had mixed responses, with partial remissions of numerous subcutaneous nodules. Sites of responsive disease included primarily the skin, but ileal, breast, and a liver metastasis also responded. Removal of residual lesions in patients with partial remissions, whose other lesions had disappeared during treatment, led to long disease-free survivals. The median duration of remission was 17 months, with four of the five responders alive for at least 24 months after treatment. An increase in precursors of cytolytic T cells (CTLs) correlated with clinical outcome, when complete, partial, and mixed responses and long-term stability were considered. The CTLs recognized melanoma-associated antigens on many cell lines, but not other types of tumor or normal lymphocytes. Skin-test reactivity to melanoma antigens and serum antibodies against the melanoma cells was unrelated to clinical response. Toxicity was minimal, restricted largely to minor soreness at the site of injection. Only five patients, four of whom were treated with repeated courses, developed severe granulomas. These results confirm that active-specific immunization with allogeneic lysates of melanoma administered with the adjuvant DETOX can induce immunity to melanoma, and can induce regressions of disease in a proportion of patients with metastatic disease with little toxicity.
Inhibition of Prolyl Hydroxylase Protects against 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Neurotoxicity (2009)

Hypoxia-inducible factor (HIF) plays an important role in cell survival by regulating iron, antioxidant defense, and mitochondrial function. Pharmacological inhibitors of the iron-dependent enzyme class prolyl hydroxylases (PHD), which target alpha subunits of HIF proteins for degradation, have recently been demonstrated to alleviate neurodegeneration associated with stroke and hypoxic-ischemic injuries. Here we report that inhibition of PHD by 3,4-dihydroxybenzoate (DHB) protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigral dopaminergic cell loss and up-regulates HIF-1alpha within these neurons. Elevations in mRNA and protein levels of HIF-dependent genes heme oxygenase-1 (Ho-1) and manganese superoxide dismutase (Mnsod) following DHB pretreatment alone are also maintained in the presence of MPTP. MPTP-induced reductions in ferroportin and elevations in nigral and striatal iron levels were reverted to levels comparable with that of untreated controls with DHB pretreatment. Reductions in pyruvate dehydrogenase mRNA and activity resulting from MPTP were also found to be attenuated by DHB. In vitro, the HIF pathway was activated in N27 cells grown at 3% oxygen treated with either PHD inhibitors or an iron chelator. Concordant with our in vivo data, the MPP(+)-elicited increase in total iron as well as decreases in cell viability were attenuated in the presence of DHB. Taken together, these data suggest that protection against MPTP neurotoxicity may be mediated by alterations in iron homeostasis and defense against oxidative stress and mitochondrial dysfunction brought about by cellular HIF-1alpha induction. This study provides novel data extending the possible therapeutic utility of HIF induction to a Parkinson disease model of neurodegeneration, which may prove beneficial not only in this disorder itself but also in other diseases associated with metal-induced oxidative stress.
A Systems Immunology Approach to the Host-Tumor Interaction: Large-Scale Patterns of Natural Autoantibodies Distinguish Healthy and Tumor-Bearing Mice (2009)

Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1) mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2) the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3) curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen) as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase). Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System-wide profiling of autoantibody repertoires can be informative.