gebhart/patrepeval huggingface dataset:
A Link between PDL1 and T Regulatory Cells in Fetomaternal Tolerance (2007)

Acceptance of the fetus expressing allogeneic paternal Ags by the mother is a physiologic model of transplantation tolerance. Various mechanisms contribute to fetal evasion from immune attack by maternal leukocytes. We have recently demonstrated that the inhibitory costimulatory molecule PDL1 plays a critical role in fetomaternal tolerance in that PDL1 blockade or deficiency resulted in decreased allogeneic fetal survival rates. CD4(+)CD25(+) T regulatory cells (Tregs) have also been demonstrated to play an important role in fetomaternal tolerance. Since PDL1 is expressed on Tregs, we explored the interactions between PDL1 and Tregs in vivo in a mouse model of fetomaternal tolerance. Depletion of CD25(+) T cells abrogated the effect of anti-PDL1 Ab indicating that the effect of PDL1 is possibly mediated by CD25(+) Tregs. Adoptive transfer of Tregs from wild-type but not PDL1-deficient mice into PDL1-deficient recipients significantly improved fetal survival. The frequency, phenotype and placental trafficking of Tregs from PDL1-deficient mice were similar to those of wild-type controls, but were defective in inhibiting alloreactive Th1 cells in vitro. This is the first report providing evidence for a link between PDL1 and T regulatory cells in mediating fetomaternal tolerance.
Intracerebral grafting of neuronal cell suspensions. VIII. Survival and growth of implants of nigral and septal cell suspensions in intact brains of aged rats. (1983)

Neuronal cell suspensions prepared from the ventral mesencephalon and the septal-diagonal band area of rat embryos were implanted into the depth of the intact neostriatum or hippocampus of 21-23 month old female rats. Graft survival, assessed 3-4 months after grafting, was comparable to that seen in our previous studies of young adult recipients. Fibre outgrowth into the host brain was evaluated in animals which were subjected to lesions of the intrinsic nigrostriatal or septohippocampal system 6-10 days before killing. Dense dopamine fibre outgrowth was seen within a zone of up to about 1 mm radius around the nigral implants, and dense growth of acetylcholine esterase (AChE) positive fibres occurred up to about 2 mm away from the septal implants. The overall magnitude of fibre outgrowth was less than that generally seen in previously denervated targets in young adult recipients, but it appeared to be as extensive as in young recipients when the grafts are placed in non-denervated targets. The distribution of the AChE-positive fibres from the septal implants in the host hippocampus suggested that the pattern found in the non-denervated target of the aged recipients was more diffuse, and partly different, from normal, and that age-dependent synapse loss in intrinsic connections may influence the patterning of the graft-derived innervation.
Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. (1997)

The highly regulated secretion of effector cytokines by CD4+ T cells plays a critical role in immune protection against pathogens such as cytomegalovirus. Here, we directly compare the frequency and functional characteristics of cytomegalovirus-specific CD4+ memory/effector T cells in normal and HIV+ subjects using a novel, highly efficient multiparameter flow cytometric assay that detects the rapid intracellular accumulation of cytokine(s) after short-term (6 h) in vitro antigen stimulation. Responses in this assay correlate precisely with independent measures of sensitization history (e.g., seroreactivity), and allow the simultaneous assessment of multiple cytokines in single effector T cells. Healthy HIV- individuals manifested an average of 0.71, 0.72, 0.38, and 0.06% CD4+ T cells responding to cytomegalovirus with gamma-IFN, TNF-alpha, IL-2, and IL-4 production, respectively, with the simultaneous production of gamma-IFN, TNF-alpha, and IL-2 being the most common effector phenotype. Significantly, overall cytomegalovirus-specific CD4+ effector frequencies were markedly higher among 40% of HIV+ subjects (2.7-8.0%), and demonstrated a predominately polarized gamma-IFN+/TNF-alpha+/IL-2-/IL-4- phenotype. In contrast, CD4+ effector frequencies for heterologous, nonubiquitous viruses such as the mumps virus were low or absent in the HIV+ group. These data suggest the existence of homeostatic mechanisms in HIV disease that selectively preserve memory T cell populations reactive with ubiquitous pathogens such as cytomegalovirus-likely at the expense of T cell memory to more sporadically encountered infectious agents.
Effects of Brimonidine on Aqueous Humor Dynamics in Human Eyes (1995)

The brimonidine-induced reduction in IOP in humans is associated with a decrease in aqueous flow and an increase in uveoscleral outflow. The decrease in IOP and aqueous flow in the contralateral control eye on day 8 compared with the baseline day suggests a mild contralateral effect.
Structural Flexibility of Chiral Macroaggregates of Light-Harvesting Chlorophyll a/b Pigment−Protein Complexes. Light-Induced Reversible Structural Changes Associated with Energy Dissipation (1996)

In this paper, we show that stacked lamellar aggregates of the purified chlorophyll a/b light-harvesting antenna complexes (LHCII) and granal thylakoid membranes are capable of undergoing light-induced reversible changes in the chiral macroorganization of the chromophores as well as in the photophysical pathways. In granal thylakoids, the light-induced reversible structural changes, detected by circular dichroism (CD) measurements, are accompanied by reversible changes in the fluorescence yield that indicate an increased dissipation of the excitation energy. These changes become gradually more significant in excess light compared to nonsaturating light intensities, and can be eliminated by suspending the membranes in hypotonic, low-salt medium in which the chiral macroaggregates are absent. In lamellar aggregates of LHCII, the light-induced reversible changes of the main, nonexcitonic CD bands are also accompanied by reversible changes in the fluorescence yield. In small aggregates and trimers, no light-induced delta CD occurs, and the fluorescence changes are largely irreversible. It is proposed that the structural changes are induced by thermal effects due to the excess light energy absorbed by the pigments. Our data strongly suggest that the structure and function of the antenna system of chloroplasts can be regulated by the absorption of excess light energy with a mechanism independent of the operation of the photochemical apparatus.
Concomitant loss of transforming growth factor (TGF)-beta receptor types I and II in TGF-beta-resistant cell mutants implicates both receptor types in signal transduction. (1990)

A panel of 71 chemically mutagenized Mv1Lu mink lung epithelial cell clones were selected based on their resistance to the growth inhibitory action of transforming growth factor beta 1 (TGF-beta 1) and TGF-beta 2. Characterization of TGF-beta receptors in these mutants indicates that the TGF-beta-binding membrane proteoglycan, betaglycan, is apparently normal in all of them. However, 14 of the mutant clones are defective in TGF-beta receptor type I, and 22 clones are simultaneously defective in receptor types I and II. The clones with type I receptor defects fall into two distinct phenotypes, called R and LR. The R phenotype is characterized by the lack of detectable type I receptors, and has been previously described (Boyd, F. T., and Massagué, J. (1989) J. Biol. Chem. 264, 2272-2278). LR mutants are characterized by expression of low levels of type I receptor and are, like the R mutants, completely resistant to growth inhibition by TGF-beta 1 or -beta 2. Mutant clones that are simultaneously defective in receptor types I and II fall into three distinct phenotypes. These included DRa mutants which are characterized by lack of detectable receptor types I and II, DRb mutants which are characterized by low expression of both receptor types and an anomalously fast electrophoretic mobility of the type II receptor protein. All mutants that have a low level of type II receptor are also defective in type I receptor. In addition to the loss of growth inhibitory response, the receptor-defective mutants described here have lost all other responses to TGF-beta 1 and -beta 2 known to occur in parental Mv1Lu cells. The defects present in these mutant clones are not encountered in clones isolated from nonmutagenized parental Mv1Lu cells or in mutagenized cells that had not been exposed to selection with TGF-beta. The results implicate TGF-beta receptor types I and II in the mediation of a common set of cellular responses to TGF-beta. Furthermore, the high relative frequency of isolation of DR mutants raises the possibility that receptor types I and II interact as part of a common signaling TGF-beta receptor complex.
Ultrafast Nonlinear Spectroscopic Techniques in the Gas Phase and Their Density Matrix Representation (2002)

We survey the possible time-resolved three pulse nonlinear spectroscopic techniques and their application to gas-phase samples. The role of each of the interacting electric fields is specified, and the nature of the signal is interpreted using the density matrix representation. Simulations of these nonlinear optical signals are based on the perturbative solution of the Liouville equation for the density matrix to third order in the applied fields. We present closed expressions for the integrated and frequency dispersed signals that identify the type of molecular response for each technique and give the signal dependence on the various time delays between laser pulses. We choose a simple experimental system, two-electronic states coupled to a single vibrational mode of diatomic iodine, with weak dephasing, to illustrate various molecular polarization responses in four-wave mixing experiments including pump−probe, reverse transient grating, and photon echo. These signals and their simulations illustrate how the time delays between pulses can be effectively used to control the optical response of the molecular system.
Nh125 Kills Methicillin-Resistant Staphylococcus Aureus Persisters by Lipid Bilayer Disruption (2016)

NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner.
Probing lethal metabolic perturbations in plants with chemical inhibition of dehydroquinate synthase (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProbing lethal metabolic perturbations in plants with chemical inhibition of dehydroquinate synthaseD. L. Pompliano, L. M. Reimer, S. Myrvold, and J. W. FrostCite this: J. Am. Chem. Soc. 1989, 111, 5, 1866–1871Publication Date (Print):March 1, 1989Publication History Published online1 May 2002Published inissue 1 March 1989https://pubs.acs.org/doi/10.1021/ja00187a049https://doi.org/10.1021/ja00187a049research-articleACS PublicationsRequest reuse permissionsArticle Views115Altmetric-Citations15LEARN 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
Gastric Inhibitory Polypeptide as an Endogenous Factor Promoting New Bone Formation after Food Ingestion (2006)

Calcium plays a fundamental role as second messenger in intracellular signaling and bone serves as the body's calcium reserve to tightly maintain blood calcium levels. Calcium in ingested meal is the main supply and inadequate calcium intake causes osteoporosis and bone fracture. Here, we describe a novel mechanism of how ingested calcium is deposited on bone. Meal ingestion elicits secretion of the gut hormone gastric inhibitory polypeptide (GIP) from endocrine K cells in the duodenum. Bone histomorphometrical analyses revealed that bone formation parameters in the mice lacking GIP receptor (GIPR(-/-)) were significantly lower than those of wild-type (GIPR(+/+)) mice, and that the number of osteoclasts, especially multinuclear osteoclasts, was significantly increased in GIPR(-/-) mice, indicating that GIPR(-/-) mice have high-turnover osteoporosis. In vitro examination showed the percentage of osteoblastic cells undergoing apoptosis to be significantly decreased in the presence of GIP. Because GIPR(-/-) mice exhibited an increased plasma calcium concentration after meal ingestion, GIP directly links calcium contained in meal to calcium deposition on bone.
Identification of a Severe Acute Respiratory Syndrome Coronavirus-Like Virus in a Leaf-Nosed Bat in Nigeria (2010)

Bats are reservoirs for emerging zoonotic viruses that can have a profound impact on human and animal health, including lyssaviruses, filoviruses, paramyxoviruses, and severe acute respiratory syndrome coronaviruses (SARS-CoVs). In the course of a project focused on pathogen discovery in contexts where human-bat contact might facilitate more efficient interspecies transmission of viruses, we surveyed gastrointestinal tissue obtained from bats collected in caves in Nigeria that are frequented by humans. Coronavirus consensus PCR and unbiased high-throughput pyrosequencing revealed the presence of coronavirus sequences related to those of SARS-CoV in a Commerson's leaf-nosed bat (Hipposideros commersoni). Additional genomic sequencing indicated that this virus, unlike subgroup 2b CoVs, which includes SARS-CoV, is unique, comprising three overlapping open reading frames between the M and N genes and two conserved stem-loop II motifs. Phylogenetic analyses in conjunction with these features suggest that this virus represents a new subgroup within group 2 CoVs.
Lesion‐induced changes of electrophysiological properties in astrocytes of the rat dentate gyrus (1999)

Reorganization of the adult dentate gyrus following unilateral entorhinal cortex lesion (ECL) is a well-established model for studying mechanisms of trauma-induced neuronal plasticity. The lesion induces deafferentiation of the outer molecular layer, which is accompanied by a strong astroglial reaction. This glial response is thought to contribute to subsequent repair processes, but the underlying mechanisms are poorly understood. In this study we addressed the question whether denervation leads to modifications in the electrophysiological properties of astrocytes, assuming that such changes might be involved in the remodeling of neural circuitry. Patch-clamp recordings were obtained from astrocytes in the dentate gyrus of adult rats that underwent ECL and compared to corresponding data from control animals. We observed a significant reduction of inward rectifier K+ current densities, a positive shift of resting potentials, and an increase in input resistance in astrocytes of the denervated molecular layer. Current densities were reduced between 6 and 19 days postlesion (dpl), reaching a minimum at 10 dpl. Voltage-gated outward K+ currents were not affected by the lesion. Inward rectifier K+ currents increase with maturation in astrocytes. Thus, our results provide evidence that, following ECL, mature astrocytes dedifferentiated and readapted an immature current pattern. Presumably, these changes lead to stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, which in turn might enhance the synthesis of neurotrophic factors and contribute to a permissive environment for neuronal reorganization. GLIA 28:166–174, 1999. © 1999 Wiley-Liss, Inc.
A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension. (2011)

The standardized Eucommia extract reduced BP and has beta-adrenergic blocking activity. Eucommia may be an appropriate nutraceutical intervention for prehypertension.
Shape control and applications of nanocrystals (2002)

Inorganic nanocrystals with well-defined shapes are important for understanding basic size-dependent scaling laws, and may be useful in a wide range of applications. Methods for controlling the shapes of inorganic nanocrystals are evolving rapidly. This paper will focus on how we currently control the shape of nanocrystals and this will be illustrated using CdSe and Co nanocrystals as examples for semiconductors and for metals. These materials show a more pronounced variation of fundamental properties with aspect ratio. However, to take advantage of these shape-dependent properties in possible applications, several challenges need to be overcome. Issues such as alignment, high quantum yield and photostability and precise control of three-dimensional structures need to be addressed. These challenges, as well as several potential applications, will be described briefly.
Adaptive identity and access management—contextual data based policies (2016)

Due to compliance and IT security requirements, company-wide identity and access management within organizations has gained significant importance in research and practice over the last years. Companies aim at standardizing user management policies in order to reduce administrative overhead and strengthen IT security. These policies provide the foundation for every identity and access management system no matter if poured into IT systems or only located within responsible identity and access management (IAM) engineers’ mind. Despite its relevance, hardly any supportive means for the automated detection and refinement as well as management of policies are available. As a result, policies outdate over time, leading to security vulnerabilities and inefficiencies. Existing research mainly focuses on policy detection and enforcement without providing the required guidance for policy management nor necessary instruments to enable policy adaptibility for today’s dynamic IAM. This paper closes the existing gap by proposing a dynamic policy management process which structures the activities required for policy management in identity and access management environments. In contrast to current approaches, it utilizes the consideration of contextual user management data and key performance indicators for policy detection and refinement and offers result visualization techniques that foster human understanding. In order to underline its applicability, this paper provides an evaluation based on real-life data from a large industrial company.
Remote estimation of blood pulse pressure via temporal tracking of reflected secondary speckles pattern (2010)

We present a novel technique for remote noncontact blood pulse pressure measurement. It is based on tracking both temporal and amplitude changes of reflected secondary speckle produced in human skin when illuminated by a laser beam. The implemented technique extracts the difference between the systolic and the diastolic blood pressure. Experimental results are presented showing good agreement when compared with conventional measurement methods.
Glu 87 of Channelrhodopsin‐1 Causes pH‐dependent Color Tuning and Fast Photocurrent Inactivation† (2009)

Channelrhodopsins (ChR1 and ChR2) are directly light-gated ion channels acting as sensory photoreceptors in the green alga Chlamydomonas reinhardtii. These channels open rapidly after light absorption and both become permeable for cations such as H(+), Li(+), Na(+), K(+) and Ca(2+). K(m) for Ca(2+) is 16.6 mm in ChR1 and 18.3 mm in ChR2 whereas the K(m) values for Na(+) are higher than 100 mm for both ChRs. Action spectra of ChR1 peak between 470 and 500 nm depending on the pH conditions, whereas ChR2 peaks at 470 nm regardless of the pH value. Now we created two chimeric ChRs possessing helix 1-5 of ChR1 and 6, 7 of ChR2 (ChR1/2(5/2)), or 1, 2 from ChR1 and 3-7 from ChR2 (ChR1/2(2/5)). Both ChR-chimera still showed pH-dependent action spectra shifts. Finally, a mutant ChR1E87Q was generated that inactivated only slowly in the light and showed no spectral shift upon pH change. The results indicate that protonation/deprotonation of E87 in helix 1 alters the chromophore polarity, which shifts the absorption and modifies channel inactivation accordingly. We propose a trimodal counter ion complex for ChR1 but only a bimodal complex for ChR2.
Antibody‐mediated signaling through PD‐1 costimulates T cells and enhances CD28‐dependent proliferation (2005)

Programmed death-1 (PD-1, CD279) is a molecule expressed on activated T, B and myeloid cells. The role of the interaction of PD-1 ligands (PD-L1 and PD-L2) with PD-1 receptor and the type of signals (costimulatory or inhibitory) that are delivered is a subject of intense debate. Our study has characterized two monoclonal antibodies (mAb) against murine PD-1, termed clone 1H10 and clone 4F10, that recognized different epitopes from that of anti-PD-1, clone J43. We showed that neither of them inhibited anti-CD3-mediated proliferation, but 1H10 mAb induced direct T cell proliferation in the absence of any other stimulus. Moreover, PD-1 engagement with 1H10 mAb costimulated anti-CD3-mediated proliferation and enhanced anti-CD3/CD28 proliferation on both CD4+ and CD8+ T cells in the low range of anti-CD3 concentrations. Anti-PD-1-mediated proliferation induced with 1H10 mAb was also observed in vivo on CD4+ and CD8+ T cells, when CFSE-labeled splenocytes were adoptively transferred to irradiated syngeneic and allogeneic recipients. Overall, our data indicate that PD-1 might not only deliver negative signals to T cells upon interaction through one of its ligands, PD-L1 as reported, but also could costimulate T cells, suggesting a dual potential functional activity of the extracellular domains of this receptor.
TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms (2009)

The mechanisms that generate itch are poorly understood at both the molecular and cellular levels despite its clinical importance. To explore the peripheral neuronal mechanisms underlying itch, we assessed the behavioral responses (scratching) produced by s.c. injection of various pruritogens in PLCbeta3- or TRPV1-deficient mice. We provide evidence that at least 3 different molecular pathways contribute to the transduction of itch responses to different pruritogens: 1) histamine requires the function of both PLCbeta3 and the TRPV1 channel; 2) serotonin, or a selective agonist, alpha-methyl-serotonin (alpha-Me-5-HT), requires the presence of PLCbeta3 but not TRPV1, and 3) endothelin-1 (ET-1) does not require either PLCbeta3 or TRPV1. To determine whether the activity of these molecules is represented in a particular subpopulation of sensory neurons, we examined the behavioral consequences of selectively eliminating 2 nonoverlapping subsets of nociceptors. The genetic ablation of MrgprD(+) neurons that represent approximately 90% of cutaneous nonpeptidergic neurons did not affect the scratching responses to a number of pruritogens. In contrast, chemical ablation of the central branch of TRPV1(+) nociceptors led to a significant behavioral deficit for pruritogens, including alpha-Me-5-HT and ET-1, that is, the TRPV1-expressing nociceptor was required, whether or not TRPV1 itself was essential. Thus, TRPV1 neurons are equipped with multiple signaling mechanisms that respond to different pruritogens. Some of these require TRPV1 function; others use alternate signal transduction pathways.