gebhart/patrepeval huggingface dataset:
Mechanisms of Autoimmunity in the Context of T‐Cell Tolerance: Insights from Natural and Transgenic Animal Model Systems (1990)

There are a number of mechanisms which cooperate to produce and maintain T-cell tolerance. First, and perhaps most important, is the clonal deletion in the thymus of T cells with high affinity for self antigens. However, to ensure that a wide repertoire of T cells is available in the periphery to combat foreign antigens, the threshold of clonal deletion may be set low enough so that T cells whose TCR's have sub-threshold affinity for self antigens mature and migrate to the periphery. T cells which recognize self antigen-derived peptides not expressed or presented in the thymus will also fail to be deleted. For those self-reactive T cells which are not deleted in the thymus, other mechanisms may produce tolerance, including an undefined alteration of signalling pathways which produces clonal anergy, and lowering the avidity of the TCR for its ligand by downregulating coreceptor and accessory molecules. Active suppression of T-cell responses in another well-described phenomenon whose mechanism is undefined. From our observations with the model systems discussed here, we have observed three distinct mechanisms by which T-cell tolerance can be circumvented, allowing autoimmune phenomena to occur. These mechanisms may have relevance for different types of autoimmune diseases seen in humans. In gld mice, the autoimmune disease seems to be related to a global defect in T-cell differentiation and function, which allows for the expansion of autoimmune B cells. While we showed that clonal deletion of V beta-bearing T cells is appropriate in certain cases, aberrant lymphokine secretion by the abnormal T cells or disruption of immune system regulation are most probably responsible for allowing autoantibody production. While human lupus erythematosis shares much of the pathology of lpr and gld mice, there is no expansion of T cells with a similar phenotype in human lupus. There are environmental factors which must play a role in the development of human lupus, since the incidence of the disease does not follow an absolute genetic pattern. The escape from clonal deletion and subsequent reactivation of autoimmune T cells which we observed in V beta 8.1 TCR-transgenic mice can be a model for human autoimmune diseases such as multiple sclerosis and type I diabetes, in which T cells are directed against a specific autoantigen. According to this model, susceptibility loci for autoimmune disease such as the MHC would function by producing different repertoires of T cells which in some cases could gain autoreactivity following activation.(ABSTRACT TRUNCATED AT 400 WORDS)
Probenpräparation für die Rückstreuelektronen-Kikuchi-Beugung (Electron Backscatter Diffraction, EBSD) - Teil Il: Keramiken / Specimen Preparation for Electron Backscatter Diffraction (EBSD) - Part Il: Ceramics (2002)

Article Probenpräparation für die Rückstreuelektronen-Kikuchi-Beugung (Electron Backscatter Diffraction, EBSD) - Teil Il: Keramiken / Specimen Preparation for Electron Backscatter Diffraction (EBSD) - Part Il: Ceramics was published on December 1, 2002 in the journal Practical Metallography (volume 39, issue 12).
ChemInform Abstract: General Approach to the Synthesis of Polyquinenes. Part 8. Synthesis of Triquinacene, 1,10‐Dimethyltriquinacene, and 1,10‐Cyclohexanotriquinacene. (1989)

Abstract Triquinacene (IXa) is synthesized starting from a Weiss reaction of glyoxal (I) with the oxoglutarate (II) via the intermediates shown in the scheme.
Finding protocol manipulation attacks (2011)

We develop a method to help discover manipulation attacks in protocol implementations. In these attacks, adversaries induce honest nodes to exhibit undesirable behaviors by misrepresenting their intent or network conditions. Our method is based on a novel combination of static analysis with symbolic execution and dynamic analysis with concrete execution. The former finds code paths that are likely vulnerable, and the latter emulates adversarial actions that lead to effective attacks. Our method is precise (i.e., no false positives) and we show that it scales to complex protocol implementations. We apply it to four diverse protocols, including TCP, the 802.11 MAC, ECN, and SCTP, and show that it is able to find all manipulation attacks that have been previously reported for these protocols. We also find a previously unreported attack for SCTP. This attack is a variant of a TCP attack but must be mounted differently in SCTP because of subtle semantic differences between the two protocols.
In Silico Theoretical Molecular Modeling for Alzheimer’s Disease: The Nicotine-Curcumin Paradigm in Neuroprotection and Neurotherapy (2011)

The aggregation of the amyloid-β-peptide (AβP) into well-ordered fibrils has been considered as the key pathological marker of Alzheimer's disease. Molecular attributes related to the specific binding interactions, covalently and non-covalently, of a library of compounds targeting of conformational scaffolds were computed employing static lattice atomistic simulations and array constructions. A combinatorial approach using isobolographic analysis was stochastically modeled employing Artificial Neural Networks and a Design of Experiments approach, namely an orthogonal Face-Centered Central Composite Design for small molecules, such as curcumin and glycosylated nornicotine exhibiting concentration-dependent behavior on modulating AβP aggregation and oligomerization. This work provides a mathematical and in silico approach that constitutes a new frontier in providing neuroscientists with a template for in vitro and in vivo experimentation. In future this could potentially allow neuroscientists to adopt this in silico approach for the development of novel therapeutic interventions in the neuroprotection and neurotherapy of Alzheimer's disease. In addition, the neuroprotective entities identified in this study may also be valuable in this regard.
Synthesis of Isoindolo[2,1-a]indoles by the Palladium-Catalyzed Annulation of Internal Alkynes (1999)

A wide variety of substituted isoindolo[2,1-a]indoles have been prepared in good to excellent yields by the palladium-catalyzed annulation of internal alkynes by imines derived from o-iodoanilines and benzaldehydes. The mechanism of this interesting annulation process appears to involve (1) oxidative addition of the aryl iodide to Pd(0), (2) alkyne insertion, (3) addition of the resulting vinylic palladium intermediate to the C−N double bond of the imine, (4) either electrophilic palladation of the resulting σ-palladium intermediate onto the adjacent aromatic ring originating in the internal alkyne or oxidative addition of the neighboring aryl carbon−hydrogen bond, and (5) reductive elimination of the tetracyclic product and Pd(0).
Increased Growth Inhibitory Effects on Human Cancer Cells and Anti-inflammatory Potency of Shogaols from Zingiber officinale Relative to Gingerols (2009)

Ginger, the rhizome of the plant Zingiber officinale , has received extensive attention because of its antioxidant, anti-inflammatory, and antitumor activities. Most researchers have considered gingerols as the active principles and have paid little attention to shogaols, the dehydration products of corresponding gingerols during storage or thermal processing. In this study, we have purified and identified eight major components, including three major gingerols and corresponding shogaols, from ginger extract and compared their anticarcinogenic and anti-inflammatory activities. Our results showed that shogaols ([6], [8], and [10]) had much stronger growth inhibitory effects than gingerols ([6], [8], and [10]) on H-1299 human lung cancer cells and HCT-116 human colon cancer cells, especially when comparing [6]-shogaol with [6]-gingerol (IC50 of approximately 8 versus approximately 150 microM). In addition, we found that [6]-shogaol had much stronger inhibitory effects on arachidonic acid release and nitric oxide (NO) synthesis than [6]-gingerol.
Comments on "kinetic model for methanol conversion to olefins" with respect to methane formation at low conversion (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComments on "kinetic model for methanol conversion to olefins" with respect to methane formation at low conversionGraham J. Hutchings, Frank Gottschalk, and Roger HunterCite this: Ind. Eng. Chem. Res. 1987, 26, 3, 635–637Publication Date (Print):March 1, 1987Publication History Published online1 May 2002Published inissue 1 March 1987https://doi.org/10.1021/ie00063a041Request reuse permissionsArticle Views202Altmetric-Citations27LEARN 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 InReddit PDF (403 KB) Get e-Alertsclose Get e-Alerts
Identification of the β cell antigen targeted by a prevalent population of pathogenic CD8 + T cells in autoimmune diabetes (2003)

Type 1 diabetes is an autoimmune disease in which autoreactive T cells attack and destroy the insulin-producing pancreatic beta cells. CD8+ T cells are essential for this beta cell destruction, yet their specific antigenic targets are largely unknown. Here, we reveal that the autoantigen targeted by a prevalent population of pathogenic CD8+ T cells in nonobese diabetic mice is islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Through tetramer technology, IGRP-reactive T cells are readily detected in islets and peripheral blood directly ex vivo. The human IGRP gene maps to a diabetes susceptibility locus, suggesting that IGRP also may be an antigen for pathogenic T cells in human type 1 diabetes and, thus, a new, potential target for diagnostic and therapeutic approaches.
FGF-2 Supplementation Enhances Hematopoietic Differentiation of Rhesus ESC’s. (2006)

Abstract Progress toward clinical application of embryonic stem cells (ESC) derived hematopoietic cellular transplantation will require rigorous evaluation in a large animal allogeneic model such as the rhesus macaque. However, in contrast to human ESC’s (hESC’s), efforts to induce conclusive hematopoietic differentiation from rhesus ESC’s (rESC’s) have been unsuccessful. Despite their close phylogenetic relationship, subtle differences exist between the hematopoietic differentiation of rESC’s and hESC’s. We recently reported that although rESC’s have the potential for hematopoietic differentiation; they exhibit an arrest at the hematoendothelial precursor stage of hematopoietic development in culture conditions developed for hESC’s. One possible difference may be in the requirement for fibroblast growth factor (FGF) signaling. Despite documentation of its contribution to the maintenance ESC’s in an undifferentiated state, the role for FGF-2 in the hematopoietic differentiation of hESC’s and rESC’s has not been similarly examined. Given its critical role for the formation and subsequent hematopoietic differentiation of murine ESC-derived hemangioblasts, we wondered if enhanced hematopoietic differentiation from rESC’s could be achieved by culture supplementation with FGF-2. To answer this question, undifferentiated rESC’s were subjected to embryoid body (EB) differentiation with daily FGF-2 supplementation of the cytokine-rich media. Cultures were analyzed by flow cytometry after 16 days of EB culture. We found that the FGF-2 supplemented cultures appeared more robust with an overall higher numbers of cells. More importantly, a dramatic expansion of hematoendothelial precursors (Flk1hi+ VE-cadherin- CD45−), committed hematopoietic progenitors (CD34+CD45+Lin−), and hematopoietic cells (CD45+) was seen in FGF-2 supplemented cultures when compared to controls. These effects were consistent in two separate lines of rESC’s (R420 and R456). Next we wondered if the observed effect of FGF-2 on hematopoietic development was concentration-dependent. Therefore, we compared serial increases in FGF-2 concentration (0, 10, 50 and 100 ng/ml) of the EB differentiation media and found the effect to be concentration-dependent. From these results, we conclude that FGF-2 appears to play a critical role in the hematopoietic differentiation of rESC’s. Both the development of hematoendothelial precursors and the differentiation of committed hematopoietic cell types are augmented. To study this further, the significance of FGF signaling at various stages of rESC-derived hematopoietic differentiation must be evaluated. A better understanding of the requirements for FGF-2 in EB development will likely lead to improved protocols for the production of human and rhesus ESC-derived hematopoietic progenitors.
Apoptosis of bronchoalveolar lavage lymphocytes in hypersensitivity pneumonitis (2003)

The aim of this study was to look at the apoptosis of alveolar lymphocytes in hypersensitivity pneumonitis (HP). HP patients and normal unexposed controls were studied. The percentage of apoptotic lymphocytes was significantly lower in HP patients than in normal patients (37.4 +/- 3.4 versus 56.5 +/- 5.5% for Annexin V and propidium iodine detection methods and 0.4 +/- 0.1 versus 1.0 +/- 0.2% for dUTP nick end-labelling technique (TUNEL)). The proportion of bronchoalveolar lavage (BAL) lymphocytes positive for Fas antigen was significantly higher in HP patients than in normal subjects (71.7 +/- 5.4 versus 50.4 +/- 9.0%). However, no significant difference was found in the proportion of BAL lymphocytes positive for Fas ligand (FasL) between the two groups. Soluble Fas (sFas) levels in the BAL fluid of the patients and normals were 80.5 +/- 8.5 pg x mL(-1) and 23.2 +/- 3.1 pg x mL(-1), respectively. A positive correlation was found between the percentage of BAL lymphocytes and the levels of sFas for the total subjects but not within the separate study groups. The intracellular quantity of the inducible anti-apoptotic gene Bcl-xL product was significantly higher in the pulmonary lymphocytes of HP patients than in lymphocytes of the control, while no difference was found for constitutive anti-apoptotic protein (Bcl-2). In conclusion, the apoptosis of pulmonary lymphocytes is lower in hypersensitivity pneumonitis than in normal subjects. This could be explained, at least in part, by an increase of soluble Fas, the anti-apoptic gene, and Bcl-xL.
Recent Advances in the Dynamics of Single Crystal to Single Crystal Transformations in Metal—Organic Open Frameworks (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Identification of differentially‐expressed miRNAs in the subfornical organ (SFO) of the mouse brain in a slow pressor angiotensin (Ang)‐II infusion model of hypertension (2009)

Hypertension caused by systemic Ang‐II infusion is mediated by central neurogenic mechanisms. Circulating Ang‐II interfaces with central sites lacking a blood brain barrier, e.g. SFO, which may respond to chronic Ang‐II signaling by altering gene expression. Given recent evidence suggesting that altered miRNA expression is involved in cardiovascular disease, we hypothesized that miRNA expression in the SFO is altered following slow‐pressor Ang‐II infusion. Mice were implanted subcutaneously with osmominipumps for systemic delivery of saline or Ang‐II (600ng*kg‐1*min‐1) for 2wks. Microarray analyses for miRNA expression performed on RNA from SFO punches (5 mice/sample, n=3) from Ang‐II or saline‐infused mice revealed that 5 miRNAs were differentially expressed (p &lt;0.05). MiRNAs mmu‐miR‐133b, mmu‐miR‐24‐2* and mmu‐mir‐499 were down‐regulated, whereas, mmu‐miR‐712 and mmu‐miR‐193b were up‐regulated Sequence analysis revealed interactions of these miRNAs with many candidate genes involved in neuronal activation. For example, mmu‐miR‐712 interacts with CaMKIIa, glutathione peroxidase 3, and neural growth regulator 1, whereas mmu‐miR‐133b interacts with AP1 family members Tcfap2a and Tcfap2d. Our findings suggest that differential expression of miRNAs following Ang‐II infusion may contribute to changes in gene expression in the SFO that could lead to the development of hypertension.
Environmentally sustainable implementations of two-dimensional nanomaterials (2023)

Rapid advancement in nanotechnology has led to the development of a myriad of useful nanomaterials that have novel characteristics resulting from their small size and engineered properties. In particular, two-dimensional (2D) materials have become a major focus in material science and chemistry research worldwide with substantial efforts centered on their synthesis, property characterization, and technological, and environmental applications. Environmental applications of these nanomaterials include but are not limited to adsorbents for wastewater and drinking water treatment, membranes for desalination, and coating materials for filtration. However, it is also important to address the environmental interactions and implications of these nanomaterials in order to develop strategies that minimize their environmental and public health risks. Towards this end, this review covers the most recent literature on the environmental implementations of emerging 2D nanomaterials, thereby providing insights into the future of this fast-evolving field including strategies for ensuring sustainable development of 2D nanomaterials.
Impaired Hepatitis C Virus (HCV)–Specific Interferon-γ Responses in Individuals With HIV Who Acquire HCV Infection: Correlation With CD4+ T-Cell Counts (2012)

Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4(+) T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534).
Differential regulation of interleukin‐12‐and interleukin‐15‐induced natural killer cell activation by interleukin‐4 (1996)

The regulation of human natural killer (NK) cell activation is under the control of a network of regulatory signals provided by cytokines. In the present study, we investigated the functional interaction between interleukin (IL)-4 and two monocyte/macrophage-derived cytokines, IL-12 and IL-15, during the process of NK stimulation. Using freshly isolated human NK cells, we have demonstrated that IL-4 negatively regulates lymphokine-activated killer (LAK) activity induced by IL-15 against the NK-resistant Daudi target cells. In contrast, IL-4 had no effect on IL-12-stimulated LAK generation. The differential effect of IL-4 on NK cell activation by IL-12 and IL-15 correlates with its ability to increase or to down-regulate the level of tumor necrosis factor-alpha and interferon-gamma release by NK cells, respectively. In contrast, endogenous transforming growth factor-beta 1 does not appear to be involved in the IL-4 regulatory pathway. Furthermore, while IL-4 was found to decrease the basal expression of the IL-2 receptor beta subunit utilized by IL-15, it had no effect on the expression of the beta 1 chain of the IL-12 receptor compared to untreated cells. Northern blot analysis indicated that the IL-4 regulatory effect on NK lytic function was associated with its capacity to down-regulate granzyme B and perforin gene transcription in response to IL-15 and its failure to affect the expression of both gene's in response to IL-12. Together, these data suggest the existence of a distinct cross-talk between IL-4 and IL-15 or IL-12 signaling pathways during the regulation of human non-major histocompatibility complex-restricted cytotoxicity.
GTPase-activating protein interactions with the viral and cellular Src kinases. (1991)

GTPase-activating protein (GAP), which regulates the activities of Ras proteins, is implicated in mitogenic signal transduction by growth-factor receptors and oncoproteins with tyrosine kinase activity. Oncogenic viral Src (p60v-src) encoded in Rous sarcoma virus possesses elevated tyrosine kinase activity compared with its nononcogenic normal homolog, cellular Src (p60c-src). To examine molecular interactions between GAP and the two Src kinases, immunoprecipitates of Src or GAP prepared from cell lystates were resolved by gel electrophoresis and analyzed by an immunoblot procedure with antibodies to GAP or Src used as probes. Results suggest that p60c-src is associated with a complex containing GAP in immunoprecipitates from lysates of normal rat and chicken cells. However, GAP is not phosphorylated in p60c-src immunoprecipitates subjected to in vitro kinase reactions. By contrast, GAP undergoes tyrosyl phosphorylation in vitro when immunoprecipitates of p60v-src prepared from transformed cell lysates are incubated with ATP. Our findings suggest that p60v-src and p60c-src associate with complexes containing GAP and provide a biochemical link between both kinases and GAP/Ras signal transduction pathways. These results are consistent with the hypothesis that GAP has a role in mediating normal functions of p60c-src as well as oncogenic activities of p60v-src.
Biopsy-free circulating tumor DNA assay identifies actionable mutations in lung cancer (2016)

This is the first clinic-based series of NSCLC patients assessing outcomes of targeted therapies using a commercially available ctDNA assay. Over 80% of patients had detectable ctDNA, concordance between paired tissue and blood for truncal oncogenic drivers was high and patients with biomarkers identified in plasma had PFS in the expected range. These data suggest that biopsy-free ctDNA analysis is a viable first choice when the diagnostic tissue biopsy is insufficient for genotyping or at the time of progression when a repeated invasive tissue biopsy is not possible/preferred.