gebhart/patrepeval huggingface dataset:
Plasma biomarker profiles in acute exacerbation of idiopathic pulmonary fibrosis (2010)

Little is known about the pathobiology of acute exacerbation of idiopathic pulmonary fibrosis (IPF), a condition that shares clinical and histopathological features with acute lung injury. Plasma biomarkers have been well studied in acute lung injury and have provided insight into the underlying disease mechanism. The objective of this study was to determine the plasma biomarker profile of acute exacerbation of IPF and compare this profile with that of stable IPF and acute lung injury. Plasma was collected from patients with stable IPF, acute exacerbation of IPF, and acute lung injury for measurement of biomarkers of cellular activity/injury (receptor for advanced glycation endproducts, surfactant protein D, KL-6, von Willebrand factor), systemic inflammation (IL-6), and coagulation/fibrinolysis (protein C, thrombomodulin, plasminogen activator inhibitor-1). Plasma from patients with acute exacerbation of IPF showed significant elevations in markers of type II alveolar epithelial cell injury and/or proliferation, endothelial cell injury, and coagulation. This profile differed from the biomarker profile in patients with acute lung injury. These findings support the hypothesis that type II alveolar epithelial cells are centrally involved in the pathobiology of acute exacerbation of IPF. Furthermore, they suggest that acute exacerbation of IPF has a distinct plasma biomarker profile from that of acute lung injury.
IKKα, IKKβ, and NEMO/IKKγ Are Each Required for the NF-κB-mediated Inflammatory Response Program (2002)

The IKKbeta and NEMO/IKKgamma subunits of the NF-kappaB-activating signalsome complex are known to be essential for activating NF-kappaB by inflammatory and other stress-like stimuli. However, the IKKalpha subunit is believed to be dispensable for the latter responses and instead functions as an in vivo mediator of other novel NF-kappaB-dependent and -independent functions. In contrast to this generally accepted view of IKKalpha's physiological functions, we demonstrate in mouse embryonic fibroblasts (MEFs) that, akin to IKKbeta and NEMO/IKKgamma, IKKalpha is also a global regulator of tumor necrosis factor alpha- and IL-1-responsive IKK signalsome-dependent target genes including many known NF-kappaB targets such as serum amyloid A3, C3, interleukin (IL)-6, IL-11, IL-1 receptor antagonist, vascular endothelial growth factor, Ptx3, beta(2)-microglobulin, IL-1alpha, Mcp-1 and -3, RANTES (regulated on activation normal T cell expressed and secreted), Fas antigen, Jun-B, c-Fos, macrophage colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Only a small number of NF-kappaB-dependent target genes were preferentially dependent on IKKalpha or IKKbeta. Constitutive expression of a trans-dominant IkappaBalpha superrepressor (IkappaBalphaSR) in wild type MEFs confirmed that these signalsome-dependent target genes were also dependent on NF-kappaB. A subset of NF-kappaB target genes were IKK-dependent in the absence of exogenous stimuli, suggesting that the signalsome was also required to regulate basal levels of activated NF-kappaB in established MEFs. Overall, a sizable number of novel NF-kappaB/IKK-dependent genes were identified including Secreted Frizzled, cadherin 13, protocadherin 7, CCAAT/enhancer-binding protein-beta and -delta, osteoprotegerin, FOXC2 and FOXF2, BMP-2, p75 neurotrophin receptor, caspase-11, guanylate-binding proteins 1 and 2, ApoJ/clusterin, interferon (alpha and beta) receptor 2, decorin, osteoglycin, epiregulin, proliferins 2 and 3, stromal cell-derived factor, and cathepsins B, F, and Z. SOCS-3, a negative effector of STAT3 signaling, was found to be an NF-kappaB/IKK-induced gene, suggesting that IKK-mediated NF-kappaB activation can coordinately illicit negative effects on STAT signaling.
Cloning and Expression of a G Protein‐Linked Acetylcholine Receptor from Caenorhabditis elegans (1999)

We have isolated a cDNA clone from the nematode Caenorhabditis elegans that encodes a protein of greatest sequence similarity to muscarinic acetylcholine receptors. This gene codes for a polypeptide of 682 amino acids containing seven putative transmembrane domains. The amino acid identities, excluding a highly variable middle portion of the third intracellular loop, to the human m1-m5 receptors are 28-34%. When this cloned receptor was coexpressed with a G protein-gated inwardly rectifying K+ channel (GIRK1) in Xenopus oocyte, acetylcholine was able to elicit the GIRK current. This acetylcholine-induced current was substantially inhibited by the muscarinic antagonist atropine in a reversible manner. However, another muscarinic agonist oxotremorine and antagonists scopolamine and pirenzepine had little or negligible effects on this receptor. Taken together, these results suggest that the cloned gene encodes a G protein-linked acetylcholine receptor that is most similar to but pharmacologically distinct from muscarinic acetylcholine receptors.
Feature-based surface parameterization and texture mapping (2005)

Surface parameterization is necessary for many graphics tasks: texture-preserving simplification, remeshing, surface painting, and precomputation of solid textures. The stretch caused by a given parameterization determines the sampling rate on the surface. In this article, we present an automatic parameterization method for segmenting a surface into patches that are then flattened with little stretch. Many objects consist of regions of relatively simple shapes, each of which has a natural parameterization. Based on this observation, we describe a three-stage feature-based patch creation method for manifold surfaces. The first two stages, genus reduction and feature identification, are performed with the help of distance-based surface functions. In the last stage, we create one or two patches for each feature region based on a covariance matrix of the feature's surface points. To reduce stretch during patch unfolding, we notice that stretch is a 2 × 2 tensor, which in ideal situations is the identity. Therefore, we use the &lt;i&gt;Green-Lagrange tensor&lt;/i&gt; to measure and to guide the optimization process. Furthermore, we allow the boundary vertices of a patch to be optimized by adding &lt;i&gt;scaffold triangles&lt;/i&gt;. We demonstrate our feature-based patch creation and patch unfolding methods for several textured models. Finally, to evaluate the quality of a given parameterization, we describe an image-based error measure that takes into account stretch, seams, smoothness, packing efficiency, and surface visibility.
Human Treg responses allow sustained recombinant adeno-associated virus–mediated transgene expression (2013)

Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type α-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction of inflammatory cells compared with 3 month biopsies. Deep sequencing of the TCR Vβ region from muscle biopsies demonstrated a limited number of T cell clones that emerged at 3 months after vector administration and persisted for 1 year. In situ immunophenotyping revealed a substantial Treg population in muscle biopsy samples containing AAT-expressing myofibers. Approximately 10% of all T cells in muscle were natural Tregs, which were activated in response to AAV capsid. These results suggest that i.m. delivery of rAAV type 1-AAT (rAAV1-AAT) induces a T regulatory response that allows ongoing transgene expression and indicates that immunomodulatory treatments may not be necessary for rAAV-mediated gene therapy.
A major histocompatibility complex class I-like Fc receptor cloned from human placenta: possible role in transfer of immunoglobulin G from mother to fetus. (1994)

The acquisition of maternal antibodies is critical for immunologic defense of the newborn. In humans, maternal IgG is actively transported across the placenta. The receptor responsible for this transport has not been identified definitively. We report the isolation from a placental cDNA library of clones encoding the alpha-chain of an immunoglobulin G (IgG)-Fc receptor (hFcRn) that resembles a class I major histocompatibility complex antigen. The DNA and predicted amino acid sequences are very similar to those of the neonatal rat and mouse intestinal Fc receptors, rFcRn and mFcRn. These receptors mediate transport of maternal IgG from milk to the blood-stream of the suckling rat or mouse. Like rat and mouse FcRn, hFcRn binds IgG preferentially at low pH, which may imply that IgG binds hFcRn in an acidic intracellular compartment during transport across the placenta.
Towards automatic scoring of non-native spontaneous speech (2006)

This paper investigates the feasibility of automated scoring of spoken English proficiency of non-native speakers. Unlike existing automated assessments of spoken English, our data consists of spontaneous spoken responses to complex test items. We perform both a quantitative and a qualitative analysis of these features using two different machine learning approaches. (1) We use support vector machines to produce a score and evaluate it with respect to a mode baseline and to human rater agreement. We find that scoring based on support vector machines yields accuracies approaching inter-rater agreement in some cases. (2) We use classification and regression trees to understand the role of different features and feature classes in the characterization of speaking proficiency by human scorers. Our analysis shows that across all the test items most or all the feature classes are used in the nodes of the trees suggesting that the scores are, appropriately, a combination of multiple components of speaking proficiency. Future research will concentrate on extending the set of features and introducing new feature classes to arrive at a scoring model that comprises additional relevant aspects of speaking proficiency.
Surface modification of nano-silica with amides and imides for use in polyester nanocomposites (2013)

Surface modified nano-silica was synthesized through a condensation reaction of the silanol groups on the silica surface with 3-aminopropyltrimethoxysilane (APS). This primary amine offers a wide range of derivatization options and acts as a linker between a silica surface and many organic species. Quantitation of the results indicated the presence of 3–4 reactive APS groups per nm2 of silica. This implies that the silanol groups present on the surface of the silica have reacted to a high extent. APS-treated silica was further treated with a series of acid anhydrides to yield more stable amidoalkyl and imidoalkyl silica. The modified surfaces were analysed by thermogravimetric analysis (TGA), Fourier-transform infra-red (FT-IR) and solid-state 13C NMR spectroscopy techniques to study the organic content and functional composition. Results indicate that the silica particles functionalized with imidoalkylsiloxane (IASi) have much higher thermal stabilities compared to aminoalkyl functionalized silica. It was also observed that thermal stability of the IASi does not depend on the acid anhydride used for the derivatization of the APS treated silica. Furthermore we used this IASi for the synthesis of poly(ethylene terephthalate) (PET)–silica nanocomposites. Dynamic mechanical analysis revealed an enhancement of the storage modulus with increasing silica content at ambient temperature as well as above the glass-transition temperature.
Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training (2008)

While further work is required, particularly in elderly people, simple dietary and exercise strategies that may improve the maintenance of skeletal muscle mass will likely result in a decrease in the overall burden of a number of diseases and improve the quality of life as we age.
Cytotoxic Effects Induced by Docetaxel, Gefitinib, and Cyclopamine on Side Population and Nonside Population Cell Fractions from Human Invasive Prostate Cancer Cells (2010)

The present study has been undertaken to establish the therapeutic benefit of cotargeting epidermal growth factor receptor (EGFR) and sonic hedgehog pathways by using gefitinib and cyclopamine, respectively, for improving the efficacy of the current chemotherapeutic drug docetaxel to counteract the prostate cancer progression from locally invasive to metastatic and recurrent disease stages. The data from immuofluorescence analyses revealed that EGFR/Tyr(1173)-pEGFR, sonic hedgehog ligand, smoothened coreceptor, and GLI-1 were colocalized with the CD133(+) stem cell-like marker in a small subpopulation of prostate cancer cells. These signaling molecules were also present in the bulk tumor mass of CD133(-) prostate cancer cells with a luminal phenotype detected in patient's adenocarcinoma tissues. Importantly, the results revealed that the CD133(+)/CD44(high)/AR(-/low) side population (SP) cell fraction endowed with a high self-renewal potential isolated from tumorigenic and invasive WPE1-NB26 cells by the Hoechst dye technique was insensitive to the current chemotherapeutic drug, docetaxel. In contrast, the docetaxel treatment induced significant antiproliferative and apoptotic effects on the CD133(-)/CD44(low)/AR(+) non-SP cell fraction isolated from the WPE1-NB26 cell line. Of therapeutic interest, the results have also indicated that combined docetaxel, gefitinib, and cyclopamine induced greater antiproliferative and apoptotic effects on SP and non-SP cell fractions isolated from WPE1-NB26 cells than individual drugs or two-drug combinations. Altogether, these observations suggest that EGFR and sonic hedgehog cascades may represent the potential therapeutic targets of great clinical interest to eradicate the total prostate cancer cell mass and improve the current docetaxel-based therapies against locally advanced and invasive prostate cancers, and thereby prevent metastases and disease relapse.
IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection (2008)

Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.
Genetic Control of Mosquitoes (2013)

Genetics can potentially provide new, species-specific, environmentally friendly methods for mosquito control. Genetic control strategies aim either to suppress target populations or to introduce a harm-reducing novel trait. Different approaches differ considerably in their properties, especially between self-limiting strategies, where the modification has limited persistence, and self-sustaining strategies, which are intended to persist indefinitely in the target population and may invade other populations. Several methods with different molecular biology are under development and the first field trials have been completed successfully.
Y‐box factor YB‐1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI‐1 (2001)

Intrinsic or acquired resistance to chemotherapy is responsible for failure of current treatment regimens in breast cancer patients. The Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major role in the development of a multidrug-resistant tumor phenotype. In human breast cancer, overexpression and nuclear localization of YB-1 is associated with upregulation of P-glycoprotein. In our pilot study, we analyzed the clinical relevance of YB-1 expression in breast cancer (n = 83) after a median follow-up of 61 months and compared it with tumor-biologic factors already used for clinical risk-group discrimination, i.e., HER2, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1). High YB-1 expression in tumor tissue and surrounding benign breast epithelial cells was significantly associated with poor patient outcome. In patients who received postoperative chemotherapy, the 5-year relapse rate was 66% in patients with high YB-1 expression. In contrast, in patients with low YB-1 expressions, no relapse has been observed so far. YB-1 expression thus indicates clinical drug resistance in breast cancer. Moreover, YB-1 correlates with breast cancer aggressiveness: in patients not treated with postoperative chemotherapy, those with low YB-1 expression are still free of disease, whereas the 5-year relapse rate in those with high YB-1 was 30%. There was no significant correlation between YB-1 expression and either HER2 expression or uPA and PAI-1 levels. Risk-group assessment achieved by YB-1 differed significantly from that by HER2 or uPA/PAI-1. In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making.
Hepatocyte growth factor is a mitogen for Schwann cells and is present in neurofibromas (1994)

To characterize mitogens that might contribute to Schwann cell proliferation during development or in tumors, we tested the ability of hepatocyte growth factor (HGF) to stimulate Schwann cell division in vitro. HGF is a potent mitogen for purified rat Schwann cells; DNA synthesis in rat Schwann cells was stimulated 20-40-fold by 3-10 ng/ml HGF. Rat Schwann cells express c-met mRNA, encoding the HGF receptor, but not HGF mRNA, implying that HGF might act as a paracrine Schwann cell growth factor. HGF-stimulated Schwann cell proliferation differs from that of previously described Schwann cell mitogens in that its activity is abolished by forskolin and is not inhibited or potentiated by addition of transforming growth factor beta (TGF beta) or fibroblast growth factor (FGF). HGF is probably not a component of the axonal signal thought to cause Schwann cell division during development, as anti-HGF neutralizing antibodies failed to block neuron-stimulated Schwann cell proliferation. In contrast, mitogenic activity present in normal human adult nerves and in neurofibromas from patients with type 1 neurofibromatosis analyzed in the absence of forskolin is largely inhibitable by anti-HGF. Thus, HGF is a novel mitogen for Schwann cells in vitro and it is present in Schwann cell tumors, suggesting a potential role for HGF after wounding of peripheral nerves or in tumor growth.
Natural killer and lymphokine-activated killer cells require granzyme B for the rapid induction of apoptosis in susceptible target cells. (1995)

Granzyme (Gzm) B-deficient mice obtained by gene targeting were used to assess the role of Gzm B in the mechanisms used by natural killer (NK) and lymphokine-activated killer (LAK) cells to destroy target cells. Gzm B-/- NK cells, LAK cells, and cytotoxic T lymphocytes (CTL) all are defective in their ability to rapidly induce DNA fragmentation/apoptosis in susceptible target cells. This defect can be partially corrected with long incubation times of effector and target cells. Moreover, Gzm B-/- NK cells (but not CTL or LAK cells) exhibit a defect in 51Cr release from susceptible target cells. This 51Cr release defect in Gzm B-deficient NK cells is also not overcome by prolonged incubation times or high effector-to-target cell ratios. We conclude that Gzm B plays a critical and nonredundant role in the rapid induction of DNA fragmentation/apoptosis by NK cells, LAK cells, and CTL. Gzm B may have an additional role in NK cells (but not in CTL or LAK cells) for mediating 51Cr release.
RT-PCR Amplicons in the Plasma of Multiple Myeloma Patients - Clinical Relevance and Molecular Pathology (2000)

The occurrence of RNA (RT-PCR amplicons) in the plasma of 70 patients was quantified: 65 patients with multiple myeloma (MM), 3 with Waldenstrom's macroglobulinemia (WM), 2 with monoclonal gammopathy of undetermined significance (MGUS), and 50 from healthy controls. A 713nt amplicon occurred in 16/18 MM patients in relapse, 5/8 untreated patients, 2,3 WM patients and 1,2 MGUS plasmas. None of the initial specimens from 37 patients in remission nor the 50 healthy controls was positive. Homology between 4 sequenced 713nt amplicons was > 99.7% and matched (99.6%) a 704nt sequence of the flanking region of the peroxisome proliferator activator receptor gene, located on chromosome 22q11.2. A 255mer within the 713nt amplicon had a 90.2% homology with an AluSc consensus sequence. The occurrence of RNA amplicons seemed to serve as accurate surrogate markers for active disease in MM that provide new insights to the molecular pathogenesis of the disease.
New Arylthioindoles and Related Bioisosteres at the Sulfur Bridging Group. 4. Synthesis, Tubulin Polymerization, Cell Growth Inhibition, and Molecular Modeling Studies (2009)

New arylthioindoles along with the corresponding ketone and methylene compounds were potent tubulin assembly inhibitors. As growth inhibitors of MCF-7 cells, sulfur derivatives were superior or sometimes equivalent to the ketones, while methylene derivatives were substantially less effective. Esters 24, 27-29, 36, 39, and 41 showed approximately 50% of inhibition on human HeLa and HCT116/chr3 cells at 0.5 microM, and these compounds inhibited the growth of HEK, M14, and U937 cells with IC(50)'s in the 78-220 nM range. While murine macrophage J744.1 cell growth was significantly less affected (20% at higher concentrations), four other nontransformed cell lines remained sensitive to these esters. The effect of drug treatment on cell morphology was examined by time-lapse microscopy. In a protocol set up to evaluate toxicity on the Saccharomyces cerevisiae BY4741 wild type strain, compounds 24 and 54 strongly reduced cell growth, and 29, 36, and 39 also showed significant inhibition.