gebhart/patrepeval huggingface dataset:
Adoptive Transfer of Treg Cells Combined with Mesenchymal Stem Cells Facilitates Repopulation of Endogenous Treg Cells in a Murine Acute GVHD Model (2015)

Therapeutic effects of combined cell therapy with mesenchymal stem cells (MSCs) and regulatory T cells (Treg cells) have recently been studied in acute graft-versus-host-disease (aGVHD) models. However, the underlying, seemingly synergistic mechanism behind combined cell therapy has not been determined. We investigated the origin of Foxp3+ Treg cells and interleukin 17 (IL-17+) cells in recipients following allogeneic bone marrow transplantation (allo-BMT) to identify the immunological effects of combined cell therapy. Treg cells were generated from eGFP-expressing C57BL/6 mice (Tregegfp cells) to distinguish the transferred Treg cells; recipients were then examined at different time points after BMT. Systemic infusion of MSCs and Treg cells improved survival and GVHD scores, effectively downregulating pro-inflammatory Th×and Th17 cells. These therapeutic effects of combined cell therapy resulted in an increased Foxp3+ Treg cell population. Compared to single cell therapy, adoptively transferred Tregegfp cells only showed prolonged survival in the combined cell therapy group on day 21 after allogeneic BMT. In addition, Foxp3+ Treg cells, generated endogenously from recipients, significantly increased. Significantly higher levels of Tregegfp cells were also detected in aGVHD target organs in the combined cell therapy group compared to the Treg cells group. Thus, our data indicate that MSCs may induce the long-term survival of transferred Treg cells, particularly in aGVHD target organs, and may increase the repopulation of endogenous Treg cells in recipients after BMT. Together, these results support the potential of combined cell therapy using MSCs and Treg cells for preventing aGVHD.
Insulin Sensitivity from Meal Tolerance Tests in Normal Subjects: A Minimal Model Index (2000)

In this report a new approach is introduced that allows estimation of insulin sensitivity (S(I)) from orally ingested glucose during an oral glucose tolerance test (OGTT) or a meal glucose tolerance test (MGTT) in normal subjects. The method hinges on the classic minimal model of glucose kinetics that is coupled with an equation describing the rate of appearance of glucose into the circulation after oral glucose ingestion. The model provides an estimate of S(I) in a given individual based on simple area under the curve type of calculations. To prove the reliability of the new approach, MGTT studies performed in 10 normal subjects were analyzed and the S(I) index from the MGTT was compared with the S(I) index obtained in the same subjects from an insulin-modified, frequently sampled iv glucose test (FSIGT). S(I) from the MGTT was 13.6+/-3.9 x 10(-4) dL/kg x min/microU x mL and was strongly correlated to the S(I) from the FSIGT (rs = 0.89; P < 0.01). In conclusion, this study shows that in normal subjects the minimal model can be applied to a MGTT/OGTT to derive an index of insulin sensitivity that is in good agreement with the one estimated from the FSIGT. Due to its simplicity, this method has potential for use in population studies, but further investigation is required to ascertain its applicability to subjects with severe insulin resistance and impaired secretory function.
Information Transparency and Analysts' Forecasts Accuracy - An Industry Perspective (2014)

This paper examines the relationship between information transparency and analysts' forecast accuracy on the basis of industry. Using data from Compustat and I/B/E/S, we provide evidence indicating that the accuracy of analysts' earnings forecasts is lower for firms in more concentrated industries. We further discover that firms belonging to industries with government economic incentives are associated with higher forecast accuracy. With industry-level information transfer effect variable, the more information that is common to all industry members, the higher the analysts’ forecast accuracy. Additionally, more industry-level news also enables analysts to conduct more efficient evaluations of a firm's future prospects. Overall, the results indicate that higher transparency within the industry will allow analysts to forecast with higher accuracy, which will then increase market demand for analysts' reports. Thus, in the governance process of raising information transparency, competent authorities should also consider options for fostering transparency at the industrial level.
Human monoclonal rheumatoid factors derived from the polyclonal repertoire of rheumatoid synovial tissue: production and characterization. (1989)

A panel of 20 human monoclonal antibodies was produced from cells derived from the synovial tissue of two rheumatoid arthritis patients and one polyarticular juvenile rheumatoid arthritis patient. Fourteen IgM monoclonal antibodies were classical rheumatoid factors (RFs) with specificities restricted to IgG and included twelve kappa and two lambda proteins. Two of them were pan-specific for IgG and reacted with all four human subclasses. Nine showed the Ga specificity, i.e. they reacted with IgG1, IgG2 and IgG4 subclass proteins. Two showed the 'new Ga-related' specificity, i.e. they reacted with IgG1, IgG2 and IgG4 subclass proteins, and also with the Ge3m(st) allotype proteins. One RF demonstrated an anti-G3m(u) anti-allotypic specificity. Five IgM(lambda) monoclonal antibodies and one IgM(kappa) monoclonal antibody demonstrated polyreactivity against various antigens including DNA, human thyroglobulin, human serum albumin and tetanus toxoid.
Filter Characteristics Influencing Circulating Tumor Cell Enrichment from Whole Blood (2013)

A variety of filters assays have been described to enrich circulating tumor cells (CTC) based on differences in physical characteristics of blood cells and CTC. In this study we evaluate different filter types to derive the properties of the ideal filter for CTC enrichment. Between 0.1 and 10 mL of whole blood spiked with cells from tumor cell lines were passed through silicon nitride microsieves, polymer track-etched filters and metal TEM grids with various pore sizes. The recovery and size of 9 different culture cell lines was determined and compared to the size of EpCAM+CK+CD45-DNA+ CTC from patients with metastatic breast, colorectal and prostate cancer. The 8 µm track-etched filter and the 5 µm microsieve had the best performance on MDA-231, PC3-9 and SKBR-3 cells, enriching >80% of cells from whole blood. TEM grids had poor recovery of ∼25%. Median diameter of cell lines ranged from 10.9-19.0 µm, compared to 13.1, 10.7, and 11.0 µm for breast, prostate and colorectal CTC, respectively. The 11.4 µm COLO-320 cell line had the lowest recovery of 17%. The ideal filter for CTC enrichment is constructed of a stiff, flat material, is inert to blood cells, has at least 100,000 regularly spaced 5 µm pores for 1 ml of blood with a ≤10% porosity. While cell size is an important factor in determining recovery, other factors must be involved as well. To evaluate a filtration procedure, cell lines with a median size of 11-13 µm should be used to challenge the system.
Dynamics of Entangled Polymer Solutions. I. The Rouse Model (1976)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of Entangled Polymer Solutions. I. The Rouse ModelP. G. De GennesCite this: Macromolecules 1976, 9, 4, 587–593Publication Date (Print):July 1, 1976Publication History Published online1 May 2002Published inissue 1 July 1976https://pubs.acs.org/doi/10.1021/ma60052a011https://doi.org/10.1021/ma60052a011research-articleACS PublicationsRequest reuse permissionsArticle Views5758Altmetric-Citations744LEARN 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
Antigen‐specific cancer immunotherapy using a GM‐CSF secreting allogeneic tumor cell‐based vaccine (2000)

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cell-based vaccines are currently one of the major forms of cancer vaccines. However, the preparation of GM-CSF-transduced autologous tumor vaccines is time-consuming and technically challenging. In addition, the host antigen presenting cells, rather than the tumor vaccine cells themselves, present tumor-specific antigens and prime the host T cells. Therefore, we tested the efficacy of antigen-specific allogeneic tumor vaccines. We used human papillomavirus 16 (HPV-16) E7 protein as a model tumor antigen, which is associated with the development of most cervical carcinoma. B16, a C57BL/6 (H-2 b ) derived melanoma cell line, was genetically engineered to produce GM-CSF alone (B16GM), HPV-16 E7 alone (B16E7), or both (B16GME7). These vaccine cells were injected into BALB/c (H-2 d ) mice (10 6 cells/mouse). Two weeks later, mice were challenged with 10 5 live HPV-16 E7 BL-1 (H-2 d ) tumor cells and monitored for tumor progression twice weekly. To determine the effective cell population in the antitumor immunity elicited by B16GME7, we carried out in vivo antibody depletion experiments using CD4 and CD8 specific antibodies. In addition, as a measure of the immune responses produced by B16GME7, we performed an in vitro cytotoxic T lymphocyte assay using a standard chromium release method. We found that all of the mice vaccinated with B16GME7 remained tumor free 49 days post-BL-1 challenge. In contrast, mice vaccinated with B16GM and B16E7 did not show any tumor protection against a similar dose of BL-1 cells. Furthermore, the antitumor immunity produced by B16GME7 was dependent on both CD4 and CD8 T cells. In addition, E7-specific cytotoxic T lymphocyte activity could be readily demonstrated in mice immunized with B16GME7. These results suggest that allogeneic tumor cells transduced with GM-CSF and the tumor antigen, HPV-16 E7, cannot only generate an E7-specific cytotoxic T lymphocytes response in vitro, but can also elicit a potent antitumor immune response against an E7 expressing tumor in vivo. Int.
Immunotherapy with CD19-specific chimeric antigen receptor (CAR)-modified T cells of defined subset composition. (2015)

3006 Background: Genetically modified T cells derived from distinct T cell subsets differ in the capacity to persist after adoptive transfer. We are conducting the first phase I/II clinical trial in which patients (pts) with CD19+ B cell malignancies receive T cells comprised of a defined composition of CD8+ TCM and CD4+ T cells engineered to express a CD19 CAR. Methods: CD8+ TCM and CD4+ T cells were separately enriched from each patient, transduced with a CD19 CAR lentivirus and expanded in vitro. The cell product for infusion was formulated in a 1:1 ratio of CD8+:CD4+ CAR+ T cells and infused at one of three dose levels (2x105 – 2x107 CAR-T cells/kg) after lymphodepleting chemotherapy. Results: Thirty-seven pts with ALL (n = 20), NHL (n = 14) or CLL (n = 3) have been treated and 33/37 received a product that conformed to a prescribed CD8+:CD4+ composition. There was no serious acute infusional toxicity. Severe cytokine release syndrome (sCRS) consisting of fever, hypotension, coagulopathy and neurotoxicity associated with elevated serum IFN-γ and IL-6 was only observed in ALL pts with high tumor burden. One ALL patient treated at the highest cell dose died of complications associated with sCRS. No NHL or CLL pts had sCRS. Eighteen of 20 ALL pts were evaluated for response, with 15 (83%) achieving complete marrow remission by high resolution flow cytometry. Clinical responses in NHL included complete (n = 1) or partial (n = 6) remission in 7/13 pts. Two of 3 CLL pts achieved marrow remission by flow cytometry. The peak level and duration of persistence of both CD4+ and CD8+ CAR-T cells were associated with clinical response. We are investigating the impact of distinct lymphodepletion regimens on CAR-T cell proliferation and persistence in vivo. A T cell immune response to the murine CD19-specific scFv component of the CAR transgene was detected in a subset of pts with limited CAR-T cell persistence. Conclusions: Adoptive immunotherapy with CD19 CAR-T cells of defined subset composition is feasible and safe in a majority of heavily pretreated pts with refractory B cell malignancies and has potent anti-tumor activity at low cell doses. CAR-T cell doses for phase II studies in ALL and NHL cohorts have been determined. Clinical trial information: NCT01865617.
Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract (1996)

The peristaltic reflex can be evoked in the absence of input from the CNS because the responsible neural pathways are intrinsic to the intestine. Mucosal enterochromaffin cells have been postulated to be pressure transducers, which activate the intrinsic sensory neurons that initiate the reflex by secreting 5-HT. All of the criteria necessary to establish 5-HT as this transmitter have been fulfilled previously, except that no mucosal mechanism for 5-HT inactivation was known. In the current investigation, desensitization of 5-HT receptors was demonstrated to inhibit the peristaltic reflex in the guinea pig large intestine in vitro. At low concentration (1.0 nM), the 5-HT uptake inhibitor fluoxetine potentiated the reflex, but higher concentrations blocked it, suggesting that the peristaltic reflex depends on the 5-HT transporter-mediated inactivation of 5-HT. Specific (Na+ -dependent, fluoxetine-sensitive) uptake of 3H-5-HT by intestinal crypt epithelial cells was found by radioautography. mRNA encoding the neuronal 5-HT transporter was demonstrated in the intestinal mucosa by Northern analysis and located in crypt epithelial cells as well as in myenteric neurons by in situ hybridization. cDNA encoding the 5-HT transporter was cloned from the mucosa and completely sequenced. 5-HT transporter immunoreactivity was detected in crypt epithelial cells and enteric neurons. Mucosal epithelial cells thus express a plasmalemmal 5-HT transporter identical to that of serotonergic neurons. This molecule seems to play a critical role in the peristaltic reflex.
Crystal structure of prostate-specific membrane antigen, a tumor marker and peptidase (2005)

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and nonprostatic solid tumor neovasculature and is a target for anticancer imaging and therapeutic agents. PSMA acts as a glutamate carboxypeptidase (GCPII) on small molecule substrates, including folate, the anticancer drug methotrexate, and the neuropeptide N-acetyl-l-aspartyl-l-glutamate. Here we present the 3.5-A crystal structure of the PSMA ectodomain, which reveals a homodimer with structural similarity to transferrin receptor, a receptor for iron-loaded transferrin that lacks protease activity. Unlike transferrin receptor, the protease domain of PSMA contains a binuclear zinc site, catalytic residues, and a proposed substrate-binding arginine patch. Elucidation of the PSMA structure combined with docking studies and a proposed catalytic mechanism provides insight into the recognition of inhibitors and the natural substrate N-acetyl-l-aspartyl-l-glutamate. The PSMA structure will facilitate development of chemotherapeutics, cancer-imaging agents, and agents for treatment of neurological disorders.
Solventogenesis in Clostridium acetobutylicum fermentations related to carboxylic acid and proton concentrations (1988)

The mechanism primarily implicated in the solventogenesis process in batch fermentations of Clostridium acetobutylicum is examined in considerable detail. A variety of fermentations with or without pH control in the pH range of 3.7-6 have been carried out in order to examine which of a host of suspect parameters correlate with the initiation of solventogenesis. The parameters that did not correlate are the external (pH(0)) and intracellular (pH(i)) pH, and DeltapH, and the external or intracellular butyrate and acetate concentrations. Undissociated butyric acid (UBA) correlated well with the initiation of solventogenesis. A linear relationship between UBA and butanol concentrations was found at the onset of solventogenesis in all fermentations examined. The intercept of this linear relationship was 6-13mM UBA for the pH(0) range of 3.7-5 and approximately zero for pH(0) at or above 6. The required minimal UBA was interpreted as a dependency of the solventogenesis process on both H(+) and butyrate concentrations. Undissociated acetic acid was found not to correlate with the initiation of solventogenesis. Addition of acetoacetate (AA) and propionate enhanced the effect of UBA on the solventogenesis process. The action of a nonmetabolizable (FCCP) and a metabolizable (AA) uncoupler on the DeltapH, pH(0), pH(i), and solventogenesis were also studied in order to gain further understanding of the solventogenesis mechanism.
HIV Gag mRNA Transfection of Dendritic Cells (DC) Delivers Encoded Antigen to MHC Class I and II Molecules, Causes DC Maturation, and Induces a Potent Human In Vitro Primary Immune Response (2000)

Dendritic cells (DC) are the major APCs involved in naive T cell activation making them prime targets of vaccine research. We observed that mRNA was efficiently transfected, resulting in superior translation in DC compared with other professional APCs. A single stimulation of T cells by HIV gag-encoded mRNA-transfected DC in vitro resulted in primary CD4(+) and CD8(+) T cell immune responses at frequencies of Ag-specific cells (5-12.5%) similar to primary immune responses observed in vivo in murine models. Additionally, mRNA transfection also delivered a maturation signal to DC. Our results demonstrated that mRNA-mediated delivery of encoded Ag to DC induced potent primary T cell responses in vitro. mRNA transfection of DC, which mediated efficient delivery of antigenic peptides to MHC class I and II molecules, as well as delivering a maturation signal to DC, has the potential to be a potent and effective anti-HIV T cell-activating vaccine.
FDA Drug Approval Summary: Bevacizumab (Avastin®) as Treatment of Recurrent Glioblastoma Multiforme (2009)

On May 5, 2009, the U.S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin; Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiforme (GBM) with progressive disease following prior therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing corticosteroid use). Two trials evaluating bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to bevacizumab plus irinotecan treatment. All patients had received prior surgery, radiotherapy, and temozolomide. Patients with active brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%-36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0-5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%-31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4-17.4 months). Safety data were provided for the first study. The most frequently reported bevacizumab adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Grade 3-5 bevacizumab-related adverse events included bleeding/hemorrhage, central nervous system (CNS) hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation, and reversible posterior leukoencephalopathy. The attribution of certain adverse events (e.g., CNS hemorrhage, wound-healing complications, and thromboembolic events) to either bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design.
Face recognition by elastic bunch graph matching (1997)

We present a system for recognizing human faces from single images out of a large database containing one image per person. Faces are represented by labeled graphs, based on a Gabor wavelet transform. Image graphs of new faces are extracted by an elastic graph matching process and can be compared by a simple similarity function. The system differs from Lades et al. (1993) in three respects. Phase information is used for accurate node positioning. Object-adapted graphs are used to handle large rotations in depth. Image graph extraction is based on a novel data structure, the bunch graph, which is constructed from a small set of sample image graphs.
Variability at the Telomeres of the Human X/Y Pseudoautosomal Region (1986)

It has been evident for some time that the telomeres (ends) of eukaryotic chromosomes must have properties that fulfill a number of functional requirements. For example, unlike ends of chromosome fragments, telomeres protect the natural chromosome end against fusion with other chromosome ends. They are often associated with the nuclear envelope. They pose a replication problem for the cell since all known DNA polymerases require a primer and synthesize only in the 5′→3′ direction. This implies that without a special structure, only one daughter chromosome would be completely replicated, the other being shortened, compared with the parental chromosome, by excision of a primer. This shortening would occur at each cell division and could presumably not be tolerated beyond a certain point. A number of models have been suggested that circumvent this problem (Blackburn and Szostak 1984).
The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. (1999)

The progressive relationship between glucose levels and cardiovascular risk extends below the diabetic threshold.
Substrate-inducible Microsomal Aryl Hydroxylase in Mammalian Cell Culture (1968)

Abstract The aryl hydroxylase enzyme system is inducible in hamster fetus cell cultures. The enzyme system is localized in the 105,000 x g pellet (microsomal fraction), has an absolute requirement for NADPH and molecular O2, a pH optimum of pH 7.5, and a partial requirement for divalent cations. Exposure to carbon monoxide reduces the enzyme activity. Treatment with ethylenediaminetetraacetate or trypsin completely prevents enzymatic activity. The Km for the hydroxylase is approximately 0.6 µm with benzo[a]pyrene as substrate. Benz[a]anthracene, 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, dibenz[a,h]anthracene, and dibenz[a,c]anthracene are also substrates for the enzyme system. The spectrophotofluorometric determination of hydroxylated benzo[a]pyrene products is sufficiently sensitive to detect 10-12 mole per ml and, hence, has great utility in measuring the hydroxylase activity of cells grown in culture. This mammalian cell culture system is advantageous for the study of the mechanism of microsomal enzyme induction and the related areas of carcinogenesis and drug and steroid metabolism.