gebhart/patrepeval huggingface dataset:
Calcium-Dependent Paired-Pulse Facilitation of Miniature EPSC Frequency Accompanies Depression of EPSCs at Hippocampal Synapses in Culture (1996)

Two forms of evoked neurotransmitter release at excitatory synapses between cultured hippocampal neurons have been described. After an action potential, it has been shown that transmitter initially is released synchronously, and this is followed by a period of "slow" asynchronous release. The "fast" synchronous component of release at these synapses has been found routinely to demonstrate paired-pulse and tetanic depression, whereas the short-term plasticity of asynchronous release has not been investigated. In the present experiments, we have used the whole-cell patch-clamp technique to record from pairs of neurons in a low-density hippocampal culture preparation to determine both the properties and underlying mechanisms of short-term plasticity of asynchronous release. It was found that an increase in miniature EPSC (mEPSC) frequency accompanied both single and multiple stimuli, and this mEPSC increase was facilitated during paired stimuli, even when the evoked synchronous release was depressed. In addition, both the activity-dependent depression of evoked EPSCs and facilitation of asynchronous mEPSC release were dependent on Ca accumulation in the nerve terminal. However, the Ca-dependent mechanisms underlying these two processes could be distinguished by the differential effects of two membrane-permeant calcium chelators, BAPTA-AM and EGTA-AM. Frequency-dependent depression of evoked EPSCs involves a rapid rise in intraterminal Ca, which likely triggers a process that proceeds in a Ca-independent manner, whereas the asynchronous release may be linked more directly to a sustained increase in intraterminal Ca.
Graft copolymers of starch. III. Copolymerization of gelatinized wheat starch with acrylonitrile. Influence of chain modifiers on copolymer composition (1967)

Abstract A study was made of the influence of selected chain modifiers on both the molecular weight of grafted polyacrylonitrile and the grafting frequency of the starch–polyacrylo‐nitrile graft copolymer. Gelatinized wheat starch was used with ceric ammonium nitrate as the initiator. The organic chain modifiers investigated were ethyl mercaptan, 1‐dodecanethiol, methyl ethyl ketone, acetaldehyde, and chloroform. Sodium chromate, cupric bromide, cupric nitrate, cupric acetate, and cupric chloride were also tested as chain modifiers. In the presence of cupric chloride, there was a tenfold reduction in the molecular weight of grafted polyacrylonitrile; however, fewer chains were grafted to the starch backbone than were observed without cupric chloride.
Postoperative Alignment of Total Knee Replacement Its Effect on Survival (1994)

Four hundred twenty-one posterior cruciate condylar total knee arthroplasties were performed between 1975 and 1983. Anatomic alignment of the knee was recorded on follow-up evaluations from two months to 13 years postoperatively. Patients were stratified into a normal group that was 5 degrees to 8 degrees anatomic valgus, a varus group that was from 4 degrees anatomic valgus to any degree of varus, and a valgus group that was more than 9 degrees anatomic valgus. There were eight failures, five in the varus group and three in the normal group. There were no failures in the valgus group. Kaplan-Meier survival curves showed no significant difference between normal and valgus groups; however, there was a statistical difference between the valgus and varus and the normal and varus groups. A surgeon should align a total knee prosthesis in neutral or a slight amount of anatomic valgus to give the patient the best chance for long-term survival.
Comparison of histologic, biochemical, and mechanical properties of murine skin treated with the 1064‐nm and 1320‐nm Nd:YAG lasers (2005)

The goal of this study was to compare the effects of the Q-switched 1064-nm Nd:YAG laser and the 1320-nm Nd:YAG laser non-ablative treatments on mouse skin in vivo. Skin elasticity measurements were carried out with a Reviscometer, and skin samples were taken for histological study, hydroxyproline content assay and estimation of collagen type I and III. By the second month after non-ablative treatments, the 1064-nm laser treatment resulted in an average of 25% greater improvement of skin elasticity, 6% more increase of dermal thickness, and 11% higher synthesis of hydroxyproline than the 1320-nm laser. Collagen type III increased markedly after the 1064-nm laser treatment whereas more collagen type I was elicited by the 1320-nm laser. Our results demonstrated that the 1064-nm laser was more effective than the 1320-nm Nd:YAG laser in non-ablative treatments, but the results needed to be confirmed in humans. It appeared that photo-mechanic reaction could cause more collagen type III synthesis whereas the photo-thermal effect was in favor of the formation of collagen type I.
1-to-12 surface normal three-dimensional optical interconnects (1993)

We present a surface normal optical interconnect with a 1-to-12 collinear fan-out. Two types of polymer-based holograms were fabricated to provide a collinear 1-to-12 fan-out from guided mode to substrate modes and twelve 1-to-1 surface normal interconnects. Fluctuation of up to 7.2 dB for the 1-to-12 fan-out hologram was observed due to the oscillating and the film saturation effects of the transmission hologram. Diffraction efficiency better than 70% was observed for all the total internal reflection holograms. The result reported herein greatly enhanced optical signal processing capability of guided wave optical interconnects. The advantages of free space optical interconnect, such as global interconnect, three dimension, massive fan-out/fan-in capabilities, and surface normal optical interconnect, can be realized using the demonstrated architecture. The coupling from waveguide to fiber can be realized from the surface rather than the edge of a photonic integrated circuit.
Operation of mixed-culture immobilized cell reactors for the metabolism ofmeta- andpara-nitrobenzoate byComamonas Sp. JS46 andComamonas Sp. JS47 (1998)

The treatment of meta- and para-nitrobenzoic acid in an industrial wastestream by Comamonas sp. JS46 and Comamonas sp. JS47 is investigated. The most important feature of the wastestream is the constantly changing concentration ratio of the two isomers. The most extreme occurrence is considered here: the complete change in feed carbon source from one isomer to the other. A series of immobilized cell airlift reactor experiments are described to examine the operation and response of the system to these changes in the feed carbon source. Separate reactors containing each species immobilized are compared with a reactor containing both species immobilized within the same bead, and to a reactor containing both species with each species confined to separate beads. On the basis of response time necessary to recover the appropriate activity, the reactor containing both species immobilized within the same bead offers the most effective arrangement. Interactions occurring between the two organisms in the coimmobilized system, mediated by the nitrobenzoate metabolites, are discussed relative to the improved response of this arrangement. Copyright 1998 John Wiley & Sons, Inc.
Classification and Treatment of Chronic Nonhealing Wounds (1986)

Previous animal data showed that platelets contain growth factors that stimulate capillary endothelial migration (angiogenesis), fibroblast proliferation and migration, and collagen synthesis. This study utilized autologous platelet-derived wound healing factors (PDWHF) to treat 49 patients with chronic nonhealing cutaneous ulcers. Patients were classified on the basis of 20 clinical and wound status parameters to generate a wound severity index. Forty-nine patients--58% diabetic (20% with renal transplants); 16% with trauma, vasculitis, etc.; 14% with decubitus ulcers; and 6% each with venous stasis or arterial insufficiency--with a total of 95 wounds had received conventional wound care for an average of 198 weeks (range: 1-1820 weeks). After informed consent was obtained, patients received autologous PDWHF. Mean 100% healing time for all patients was 10.6 weeks. There was no abnormal tissue formation, keloid, or hypertrophic scarring. A multivariant analysis showed a direct correlation to 100% healing with initial wound size and the initiation of PDWHF therapy. This is the first clinical demonstration that locally acting growth factors promote healing of chronic cutaneous ulcers.
Fermentative lifestyle in yeasts belonging to the Saccharomyces complex (2007)

The yeast Saccharomyces cerevisiae is characterized by its ability to: (a) degrade glucose or fructose to ethanol, even in the presence of oxygen (Crabtree effect); (b) grow in the absence of oxygen; and (c) generate respiratory-deficient mitochondrial mutants, so-called petites. How unique are these properties among yeasts in the Saccharomyces clade, and what is their origin? Recent progress in genome sequencing has elucidated the phylogenetic relationships among yeasts in the Saccharomyces complex, providing a framework for the understanding of the evolutionary history of several modern traits. In this study, we analyzed over 40 yeasts that reflect over 150 million years of evolutionary history for their ability to ferment, grow in the absence of oxygen, and generate petites. A great majority of isolates exhibited good fermentation ability, suggesting that this trait could already be an intrinsic property of the progenitor yeast. We found that lineages that underwent the whole-genome duplication, in general, exhibit a fermentative lifestyle, the Crabtree effect, and the ability to grow without oxygen, and can generate stable petite mutants. Some of the pre-genome duplication lineages also exhibit some of these traits, but a majority of the tested species are petite-negative, and show a reduced Crabtree effect and a reduced ability to grow in the absence of oxygen. It could be that the ability to accumulate ethanol in the presence of oxygen, a gradual independence from oxygen and/or the ability to generate petites were developed later in several lineages. However, these traits have been combined and developed to perfection only in the lineage that underwent the whole-genome duplication and led to the modern Saccharomyces cerevisiae yeast.
Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. (1993)

In studies to determine whether Saccharomyces cerevisiae produced estrogens, the organism was grown in culture media prepared using distilled water autoclaved in polycarbonate flasks. The yeast-conditioned media showed the presence of a substance that competed with [3H]estradiol for binding to estrogen receptors (ER) from rat uterus. However, it soon became clear that the estrogenic substance in the conditioned media was not a product of the yeast grown in culture, but was leached out of the polycarbonate flasks during the autoclaving procedure. [3H]Estradiol displacement activity was monitored by ER RRA, and the active substance was purified from autoclaved medium using a series of HPLC steps. The final purified product was identified as bisphenol-A (BPA) by nuclear magnetic resonance spectroscopy and mass spectrometry. BPA could also be identified in distilled water autoclaved in polycarbonate flasks without the requirement of either the organism or the constituents of the culture medium. Authentic BPA was active in competitive RRAs, demonstrating an affinity approximately 1:2000 that of estradiol for ER. In functional assays, BPA (10-25 nM) induced progesterone receptors in cultured human mammary cancer cells (MCF-7) at a potency of approximately 1:5000 compared to that of estradiol. The BPA effect on PR induction was blocked by tamoxifen. In addition, BPA (25 nM) increased the rate of proliferation of MCF-7 cells assessed by [3H]thymidine incorporation. Thus, BPA exhibited estrogenic activity by both RRA and two functional bioresponse assays. Finally, MCF-7 cells grown in media prepared with water autoclaved in polycarbonate exhibited higher progesterone receptor levels than cells.grown in media prepared with water autoclaved in glass, suggesting an estrogenic effect of the water autoclaved in polycarbonate. Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment.
Long-lasting antitumor protection by anti-CD20 antibody through cellular immune response (2010)

The anti-CD20 monoclonal antibody (mAb) rituximab has been used successfully for lymphoma therapy for more than 10 years. Although several direct mechanisms by which anti-CD20 mAbs act have been characterized in vitro, their specific role in clinical efficacy is still debated. Little is known about the possible antitumor immune response that they may induce in patients, despite clinical data suggesting a "vaccinal" effect. We show here that an initial treatment with anti-CD20 induces protection against human CD20-expressing tumor cells and allows immunocompetent mice to survive tumor challenge. This long-lasting protection requires the presence of the Fc portion of the anti-CD20 mAb and is achieved through the induction of a cellular immune response. Only CD4(+) cells were needed at the beginning of the treatment, but both CD4(+) and CD8(+) cells were required after tumor challenge to achieve protection. Finally, we show that interleukin-2 treatment, given after tumor challenge, improves the overall survival rate, compared with that obtained by anti-CD20 treatment alone. These findings demonstrate that anti-CD20 mAbs exert therapeutic effects through the induction of an adaptive cellular immune response, aside from any direct mechanisms involving effectors from innate immunity.
Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer (2017)

<b>Purpose:</b> Immunotherapies targeting programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) demonstrate encouraging antitumor activity and manageable tolerability in non-small cell lung cancer (NSCLC), especially in patients with high tumor PD-L1 expression, as detected by companion or complementary diagnostic assays developed for individual agents. A laboratory is unlikely to use multiple assay platforms. Furthermore, commercially available diagnostic assays are not standardized, and different assay methods could lead to inappropriate treatment selection. This study establishes the extent of concordance between three validated, commercially available PD-L1 IHC diagnostic assays for NSCLC patients [Ventana SP263 (durvalumab), Dako 22C3 (pembrolizumab), and Dako 28-8 (nivolumab)].<b>Experimental Design:</b> Five hundred formalin-fixed, paraffin-embedded archival NSCLC samples were obtained from commercial sources. Stained slides were read in batches on an assay-by-assay basis by a single pathologist trained in all methods, in a Clinical Laboratory Improvements Amendments program-certified laboratory. An additional pathologist performed an independent review of 200 stained samples for each assay.<b>Results:</b> PD-L1 expression was evaluable with all assays in 493 samples. The three assays showed similar patterns of tumor membrane staining, with high correlation between percent PD-L1 staining. An overall percentage agreement of >90% was achieved between assays at multiple expression cutoffs, including 1%, 10%, 25%, and 50% tumor membrane staining.<b>Conclusions:</b> This study builds optimism that harmonization between assays may be possible, and that the three assays studied could potentially be used interchangeably to identify patients most likely to respond to anti-PD-1/PD-L1 immunotherapies, provided the appropriate clinically defined algorithm and agent are always linked. <i>Clin Cancer Res; 23(14); 3585-91. ©2017 AACR</i>.
Role of the T Cell Receptor Ligand Affinity in T Cell Activation by Bacterial Superantigens (2001)

Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3 (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands. Comparable studies using anti-TCR antibodies of known affinity confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength.
The nasal route of cerebrospinal fluid drainage in man. A light–microscope study (1994)

The drainage routes from the subarachnoid space to the nasal mucosa were investigated in autopsy material. Indian ink, applied post-mortem to the olfactory groove, promptly filled the perineurial spaces around the olfactory nerve branches in the dura, the lamina cribrosa and the submucosal tissue in the nose. In a case of recent subarachnoid haemorrhage, the perineurial spaces even around the most distal olfactory nerve branches were congested with blood and there was an abundant accumulation of red corpuscles in the apical part of the nasal mucosa. Iron-containing pigment was found in the perineurial spaces of proximal and distal olfactory nerve branches as well as in the nasal mucosal stroma in cases with older haemorrhagic lesions. The findings show that the perineurial spaces provide an efficient drainage route from the subarachnoid space to the nasal mucosa in cases with haemorrhagic cerebral lesions. A complementary drainage route for the cerebrospinal fluid was indicated by the presence of indian ink, red corpuscles and iron pigment in arachnoid villi, which penetrated the lamina cribrosa and ended in the nasal submucosal tissue. Iron in the deep cervical lymph nodes should not be taken as evidence of transport from the CNS, since iron pigment was also found in cases without intracranial haemorrhage.
Zur Kenntnis der 2‐Amino‐1.3.4‐oxdiazole, VIII. BILDUNG VON 2‐AMINO‐5‐AMINOALKYL‐1.3.4‐OXDIAZOLEN UND DEREN UMWANDLUNG IN 1.2.4‐TRIAZOLE UND TRIAZOLONE (1962)

Abstract Bei der Einwirkung von Bromcyan auf acylierte Aminosäurehydrazide bilden sich substituierte 2‐Amino‐1.3.4‐oxdiazole, die bei der Umsetzung mit primären Aminen die entsprechenden Amino‐1.2.4‐triazole liefern. Aus den Oxdiazolen entstehen in einigen Fällen beim alkalischen Verkochen Triazolone.
Effects of spinal cord stimulation on coronary blood flow velocity (1998)

The results of this study do not support the theory that the anti-ischaemic effect of SCS is dependent on an increase in coronary flow velocity.
Gel-Immobilized Microarrays of Nucleic Acids and Proteins: Production and Application for Macromolecular Research (2003)

Biochips are small platforms with spatially arrayed macromolecules (or pieces thereof) that allow the collection and analysis of large amounts of biological information. The principle of the technology is based on specific molecular recognition interactions between the arrayed macromolecules and the test molecule of interest. Classical examples of such recognition reactions are the interactions between the two complementary strands of a double-helical DNA molecule, between a single-stranded DNA stretch and the messenger RNA copied from it during transcription, between an antigen and an antibody, and between small ligands and their nucleic acid or protein partners.
CD4+ subset expression in murine candidiasis. Th responses correlate directly with genetically determined susceptibility or vaccine-induced resistance (1993)

Previous work has shown that in hybrid (BALB/cCr x DBA/2Cr)F1 mice the development of a fatal disseminated disease by systemic infection with virulent Candida albicans is associated with the detection of strong Th2-like responses. However, a predominant Th1-like response and long-lived antifungal protection are induced by vaccinating these mice with live blastospores of attenuated C. albicans strains. When injected into DBA/2Cr mice, one such live vaccine strain was found in the present study to result in a progressive disease characterized by strong Th2 responses. Elevated serum IgG1, IgA, and IgE responses, weak or absent footpad reactions, sustained production in vitro of Th2 (IL-4 and IL-10) but not Th1 (IL-2 and IFN-gamma) cytokines by CD4+ cells, and eosinophilia were all detected in DBA/2 mice after infection with the attenuated vaccine. This was in marked contrast with the development of strong Th1 responses and persistent anticandidal protection in similarly infected, H-2-compatible BALB/cCr mice. Therefore, our data suggest that the type of Th response that predominates in mice after C. albicans infection correlates with genetically determined susceptibility or vaccine-induced resistance. Moreover, the genetic control of this resistance may not be associated with the H-2 complex.
The pharmacogenetics of codeine hypoalgesia (1995)

Codeine is an old drug that is still widely used to treat mild and moderate pain. It is mainly metabolised by glucuronidation, but minor pathways are N-demethylation to norcodeine and O-demethylation to morphine. The latter pathway depends on the genetically polymorphic CYP2D6 which is absent in 7% of the white population (PM) and present in the remainder (EM). Lack of influence of codeine on experimental pain in PM as well as in EM treated with the CYP2D6 blocker quinidine, who are both practically unable to convert codeine to morphine, has supported an old hypothesis that codeine acts through metabolically formed morphine. Possibly, local codeine O-demethylation in the CNS is of major importance for its hypoalgesic effect. Such a local morphine formation from codeine, which supposedly is also catalysed by CYP2D6, could explain why the hypoalgesic effect of codeine stems from morphine despite relatively low plasma levels of morphine after standard hypoalgesic doses of codeine. Dependence of codeine hypoalgesia on morphine formation via CYP2D6 makes this effect liable to interaction with drugs that are inhibitors of CYP2D6. Examples of potent inhibitors of CYP2D6 are quinidine, some selective serotonin reuptake inhibitors and some neuroleptics. Less potent inhibitors, such as tricyclic antidepressants, will probably also reduce the pain relieving effect of codeine, since codeine has a low affinity for CYP2D6. Biosynthesis of morphine in humans may also include steps catalyse by CYP2D6. Experimental studies in large groups of EM and PM indicate that this may lead to interphenotype differences in pain tolerance.