gebhart/patrepeval huggingface dataset:
Malonate‐Induced Generation of Reactive Oxygen Species in Rat Strium Depends on Dopamine Release but Not on NMDA Receptor Activation (1999)

Intrastriatal injection of the reversible succinate dehydrogenase inhibitor malonate produces both energy depletion and striatal lesions similar to that seen in cerebral ischemia and Huntington's disease. The mechanisms of neuronal cell death involve secondary excitotoxicity and the generation of reactive oxygen species. Here, we investigated the effects of dopamine on malonate-induced generation of hydroxyl radicals and striatal lesion volumes. Using in vivo microdialysis, we found that malonate induced a 94-fold increase in extracellular striatal dopamine concentrations. This was paralleled by an increase in the generation of hydroxyl radicals. Prior unilateral lesioning of the nigrostriatal dopaminergic pathway by focal injection of 6-hydroxydopamine blocked the malonate-induced increase in dopamine concentrations and the generation of hydroxyl radicals and attenuated the lesion volume. In contrast, the NMDA receptor antagonist MK-801 attenuated malonate-induced lesion volumes but did not block the generation of hydroxyl radicals. Thus, the dopaminergic and glutamatergic pathways are essential in the pathogenesis of malonate-induced striatal lesions. Our results suggest that the malonate-induced release of dopamine but not NMDA receptor activation mediates hydroxyl radical formation.
Remote Ischemic Perconditioning Is Effective Alone and in Combination With Intravenous Tissue-Type Plasminogen Activator in Murine Model of Embolic Stroke (2012)

RIPerC is effective alone after embolic middle cerebral artery occlusion and has additive effects in combination with intravenous tPA. RIPerC may be a simple, safe, and inexpensive combination therapy with intravenous tPA.
Topographically designed analogs of [cyclic] [D-Pen2,D-Pen5]enkephalin (1991)

The conformationally restricted, cyclic disulfide-containing delta opioid receptor selective enkephalin analogue [D-Pen2,D-Pen5]enkephalin (1, DPDPE) was systematically modified topographically by addition of a methyl group at either the pro-S or pro-R position of the beta carbon of an L-Phe4 or D-Phe4 residue to give [(2S,3S)-beta-MePhe4]DPDPE (2), [(2R,3R)-beta-MePhe4]DPDPE (3), [(2S,3R)-beta-MePhe4]DPDPE (4), and [(2R,3S)-beta-MePhe4]DPDPE (5). The four corresponding isomers were prepared in which the beta-methylphenylalanine residue was p-nitro substituted, that is with a beta-methyl-p-nitrophenylalanine (beta-Me-p-NO2Phe) residue, to give [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (6), [(2R,3R)-beta-Me-p-NO2Phe4]DPDPE (7), [(2S,3R)-beta-Me-p-NO2Phe4] DPDPE (8), and [(2R,3S)-beta-Me-p-NO2Phe4]DPDPE (9), respectively. The potency and selectivity (delta vs mu opioid receptor) were evaluated by radioreceptor binding assays in the rat brain using [3H]CTOP (mu ligand) and [3H]DPDPE (delta ligand) and by bioassay with mouse vas deferens (MVD, delta receptor assay) and guinea pig ileum (GPI, mu receptor assay). The eight analogues of DPDPE showed highly variable binding and bioassay activities particularly at the delta opioid receptor (4 orders of magnitude), but also at the mu opioid receptor, which led to large differences (3 orders of magnitude) in receptor selectivity. For example, [(2S,3S)-beta-MePhe4]DPDPE (2) is 1800-fold selective in binding to the delta vs mu receptor, making it one of the most selective delta opioid receptor ligands in the enkephalin series as assessed by the rat brain binding assay, whereas the corresponding (2R,3R)-beta-Me-p-NO2Phe-containing analogue 9 is only 4.5-fold selective (nonselective) in this same assay. On the other hand, in the bioassay systems, [(2S,3S)-beta-Me-p-NO2Phe4]DPDPE (5) is more potent than DPDPE and 8800-fold selective for the MVD (delta receptor) vs the GPI (mu receptor), making it the most highly selective ligand in this series for the delta opioid receptor on the basis of these bioassays. In these assay systems, the (2R,3S)-beta-MePhe4-containing analogue 5 had very weak potency and virtually no receptor selectivity (4.4-fold). These results demonstrate that topographical modification alone in a conformationally restricted peptide ligand can significantly modulate both potency and receptor selectivity of peptide ligands that have multiple sites of biological activity and suggest that this approach may have general application to peptide ligand design.
Antibiotic treatment of experimental endocarditis due to vancomycin- and ampicillin-resistant Enterococcus faecium (1993)

We compared ciprofloxacin, rifampin, and gentamicin treatments, alone and in combination, for 5 days in the therapy of experimental aortic valve endocarditis in rats caused by a clinical isolate of vancomycin-resistant Enterococcus faecium. The MICs and MBCs of vancomycin, ciprofloxacin, rifampin, and gentamicin were 250 and > 1,000, 3.1 and 6.3, 0.098 and 1.6, and 12.5 and > 50 micrograms/ml, respectively. Infected rats were sacrificed after completing 5 days of therapy. Additional rats within each treatment group were followed for 5 days beyond the last dose of antibiotic therapy. Although survivals in the different groups were not significantly different after 5 days of therapy, survival was significantly better 5 days beyond the last dose of antibiotic therapy in rats treated with rifampin-containing regimens. The combination of ciprofloxacin and gentamicin was bactericidal in vitro and in vegetations from rats with enterococcal endocarditis. Rifampin alone was similarly bactericidal in vivo, but it was not significantly better than rifampin in combination with other antibiotics. Subpopulations resistant to rifampin, but not ciprofloxacin, were detected in the inoculum and in most vegetations during therapy. However, the combination of ciprofloxacin plus both gentamicin and rifampin reduced both the rifampin-susceptible and -resistant population in vegetations of 9 of 10 animals below the level of detection after 5 days of therapy. Nevertheless, a residual enterococcal population apparently remained in numbers of < 2 log10 CFU/g after 5 days of therapy, which resulted in relapse. Perhaps a longer course of therapy would have eliminated this residual population and improved efficacy.
HLA-DQ1 associated with reflex sympathetic dystrophy (1999)

Reflex sympathetic dystrophy (RSD) is a relatively common disabling disorder of unknown pathophysiology. From a cohort of 52 patients, carefully selected to fulfill the recently formulated diagnostic criteria for RSD, venous blood samples were taken for typing of class I and II major histocompatibility antigens. The frequency of HLA-DQ1 was found to be significantly increased compared with control frequencies. The association provides an indication for an organic basis of RSD.
Model based corner detection (2002)

A method is presented to correct an approximate polygonal sketch of an image object boundary by adjusting the location of each corner point in the sketch. The method is suitable for the segmentation of unknown images using interactive techniques, and for locating object boundaries in model-based segmentation. For each point, p, at which two lines meet in an open or closed polygonal sketch, a corner segmentation model is derived based on the angle, orientation and scale of the corner defined, and the image function f(x, y) in the immediate region about p. A corner template is then constructed and matched in a small neighborhood about p, thereby providing a corrected polygonal sketch. The segmentation model is correct in 95% of the cases, and the corner is accurately located.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
DNA targeting specificity of RNA-guided Cas9 nucleases (2013)

The Streptococcus pyogenes Cas9 (SpCas9) nuclease can be efficiently targeted to genomic loci by means of single-guide RNAs (sgRNAs) to enable genome editing1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Here, we characterize SpCas9 targeting specificity in human cells to inform the selection of target sites and avoid off-target effects. Our study evaluates >700 guide RNA variants and SpCas9-induced indel mutation levels at >100 predicted genomic off-target loci in 293T and 293FT cells. We find that SpCas9 tolerates mismatches between guide RNA and target DNA at different positions in a sequence-dependent manner, sensitive to the number, position and distribution of mismatches. We also show that SpCas9-mediated cleavage is unaffected by DNA methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize off-target modification. To facilitate mammalian genome engineering applications, we provide a web-based software tool to guide the selection and validation of target sequences as well as off-target analyses.
T‐Cell Immunodeficiency Following Cytotoxic Antineoplastic Therapy: A Review (2000)

Although cancer itself is immunosuppressive, cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. The immunodeficiency induced by cytotoxic antineoplastic therapy is primarily related to T-cell depletion, with CD4 depletion generally more severe than CD8 depletion. Myeloablative therapy, dose-intensive alkylating agents, purine nucleoside analogs, and corticosteroids substantially increase the risk of therapy-induced immunosuppression. Restoration of T-cell populations following cytotoxic antineoplastic therapy is a complex process. Efficient recovery of CD4+ T cell populations requires thymic-dependent pathways which undergo an age-dependent decline resulting in prolonged CD4+ T-cell depletion in adults following T-cell-depleting therapy. Total CD8+ T-cell numbers recover in both children and adults relatively quickly post-therapy; however, CD8+ subset disruptions often remain for a prolonged period. The clinical management of patients with therapy-induced T-cell depletion involves the maintenance of a high index of suspicion for opportunistic pathogens, irradiation of blood products, prophylaxis for viral infections, and reimmunization in selected clinical circumstances. Future research avenues include efforts to rapidly rebuild immunity following cytotoxic antineoplastic therapy so that immune-based therapies may be utilized immediately following cytotoxic therapy to target minimal residual neoplastic disease.
SIMPLIFYING NEURAL NETS BY DISCOVERING FLAT MINIMA (1994)

We present a new algorithm for finding low complexity networks with high generalization capability. The algorithm searches for large connected regions of so-called &amp;quot;flat&amp;quot; minima of the error function. In the weight-space environment of a &amp;quot;flat&amp;quot; minimum, the error remains approximately constant. Using an MDL-based argument, flat minima can be shown to correspond to low expected overfitting. Although our algorithm requires the computation of second order derivatives, it has backprop&amp;apos;s order of complexity. Experiments with feedforward and recurrent nets are described. In an application to stock market prediction, the method outperforms conventional backprop, weight decay, and &amp;quot;optimal brain surgeon&amp;quot;. 1 INTRODUCTION Previous algorithms for finding low complexity networks with high generalization capability are based on significant prior assumptions. They can be broadly classified as follows: (1) Assumptions about the prior weight distribution. Hinton and van Camp [3] and Williams [17] ass...
Osteogenesis of the mandible associated with implant reconstruction: a patient report. (1989)

A patient report is presented illustrating bone growth of the posterior mandible associated with a fixed implant reconstruction of the Brånemark type. In this instance, the mandible had grown vertically approximately 3 mm and was causing discomfort beneath the cantilever sections of the prosthesis because of gingival impingement between the restoration and the bony mandible. The literature relative to osteogenesis associated with osseointegrated implants is reviewed.
Pharmacokinetics of the novel dual endothelin receptor antagonist macitentan in subjects with hepatic or renal impairment (2013)

Macitentan is under development for the treatment of pulmonary arterial hypertension (PAH). Patients with PAH may suffer from comorbidities such as renal or hepatic impairment. Two prospective, single-center, open-label studies evaluated the pharmacokinetics of macitentan and its metabolites (pharmacologically active ACT-132577 and inactive ACT-373898) in healthy subjects and in subjects with mild, moderate, and severe hepatic impairment or severe renal function impairment (SRFI). After administering a single oral dose of 10 mg macitentan the pharmacokinetic parameters including area under the curve from zero to infinity (AUC∞) were derived from plasma concentration-time profiles. Exposure to macitentan and ACT-132577 was lower in hepatically impaired versus healthy subjects, with no correlation with the degree of hepatic impairment. Exposure to ACT-373898 was lower in subjects with moderate hepatic impairment only. Plasma concentration-time profiles for macitentan and ACT-132577 (active) were similar in healthy subjects and subjects with SRFI. AUC∞ of ACT-373898 (inactive) was 7.3-fold higher in subjects with SRFI versus healthy subjects. No safety concerns were raised in either study. Based on these observations, pharmacokinetic alterations of macitentan due to hepatic or renal function impairment are not considered clinically relevant and no dose adjustment is necessary in these patients.
Interaction of divalent manganese ion with adenosine triphosphate and related compounds (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of divalent manganese ion with adenosine triphosphate and related compoundsAnthony T. Tu, Michael J. Heller, and Alan J. JonesCite this: Biochemistry 1970, 9, 25, 4981–4986Publication Date (Print):December 8, 1970Publication History Published online1 May 2002Published inissue 8 December 1970https://pubs.acs.org/doi/10.1021/bi00827a023https://doi.org/10.1021/bi00827a023research-articleACS PublicationsRequest reuse permissionsArticle Views68Altmetric-Citations22LEARN 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
The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis (2012)

The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects.
Genetic evidence that the bacteriophage φX174 lysis protein inhibits cell wall synthesis (2000)

Protein E, a 91-residue membrane protein of phiX174, causes lysis of the host in a growth-dependent manner reminiscent of cell wall antibiotics, suggesting E acts by inhibiting peptidoglycan synthesis. In a search for the cellular target of E, we previously have isolated recessive mutations in the host gene slyD (sensitivity to lysis) that block the lytic effects of E. The role of slyD, which encodes a FK506 binding protein-type peptidyl-prolyl cis-trans isomerase, is not fully understood. However, E mutants referred to as Epos (plates on slyD) lack a slyD requirement, indicating that slyD is not crucial for lysis. To identify the gene encoding the cellular target, we selected for survivors of Epos. In this study, we describe the isolation of dominant mutations in the essential host gene mraY that result in a general lysis-defective phenotype. mraY encodes translocase I, which catalyzes the formation of the first lipid-linked intermediate in cell wall biosynthesis. The isolation of these lysis-defective mutants supports a model in which translocase I is the cellular target of E and that inhibition of cell wall synthesis is the mechanism of lysis.
Inhibition of Nitric Oxide Synthesis Reduces Infarct Size by an Adenosine-Dependent Mechanism (1995)

Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent.
Dense-Stereo and Novel-view Synthesis for Gaze Manipulation in One-to-one Teleconferencing (2003)

A new algorithm is proposed for novel-view synthesis, with particular application to teleconferencing. Given the video streams acquired by two cameras placed on either side of a computer monitor, the proposed algorithm synthesises images from a virtual camera in arbitrary position (typically located within the monitor area) to facilitate eye contact. The new technique is based on an improved, dynamic-programming, stereo algorithm for efficient novel-view generation. The two main contributions of this paper are: i) a new four-layer matching graph for dense-stereo dynamic-programming, that supports accurate occlusion labeling; ii) a compact geometric derivation for novel-view synthesis by direct projection of the minimum-cost surface. Furthermore, the paper presents an algorithm for the temporal maintenance of a background model to enhance the rendering of occlusions and reduce temporal artefacts (flicker); and a cost aggregation algorithm that acts directly in three-dimensional matching cost space. The proposed algorithm has been designed to work with input images with large disparity range, a common situation in one-to-one video-conferencing. The enhanced occlusion- handling capabilities of the new DP algorithm are evaluated against those of the most powerful state-of-the-art dynamic-programming and graph-cut techniques. A number of examples demonstrate the robustness of the algorithm to artefacts in stereo video streams. This includes demonstrations of cyclopean view synthesis in extended conversational sequences, synthesis from a freely translating virtual camera and, finally, basic 3D scene editing.