gebhart/patrepeval huggingface dataset:
Convergence of Signaling Pathways on the Activation of ERK in B Cells (2002)

The B cell receptor (BCR) initiates three major signaling pathways: the Ras pathway, which leads to extracellular signal-regulated kinase (ERK) activation; the phospholipase C-gamma pathway, which causes calcium mobilization; and the phosphoinositide 3-kinase (PI 3-kinase) pathway. These combine to induce different biological responses depending on the context of the BCR signal. Both the Ras and PI 3-kinase pathways are important for B cell development and activation. Several model systems show evidence of cross-regulation between these pathways. Here we demonstrate through the use of PI 3-kinase inhibitors and a dominant-negative PI 3-kinase construct that the BCR-induced phosphorylation and activation of ERK is dependent on PI 3-kinase. PI 3-kinase feeds into the Ras signaling cascade at multiple points, both upstream and downstream of Ras. We also show that ERK activation is dependent on phospholipase C-gamma, in keeping with its dependence on calcium mobilization. Last, the activation of PI 3-kinase itself is completely dependent on Ras. We conclude that the PI 3-kinase and Ras signaling cascades are intimately connected in B cells and that the activation of ERK is a signal integration point, since it requires simultaneous input from all three major signaling pathways.
T– and B–Cell Responses to Different Hepatitis C Virus Antigens in Patients With Chronic Hepatitis C Infection and in Healthy Anti– Hepatitis C Virus—Positive Blood Donors Without Viremi (1996)

As the host's immune response may determine the course of hepatitis C virus (HCV) infection, we studied the humoral and cellular immune responses to HCV-related antigens in subjects with different outcomes of HCV infection. Lymphoproliferative responses and circulating antibodies to a panel of HCV core- and E1-related 25-mer peptides were examined in 10 healthy anti-HCV-seropositive blood donors (group A) and in 29 patients with chronic hepatitis C (group B). In addition, cellular recognition of recombinant HCV proteins (core, NS3, NS4A, NS5A, NS5B) were investigated. In group A, stronger T-cell responses were detected against both HCV proteins (core, P = .03; NS4, P = .005; NS5B, P = .03) and peptides. Proliferation was induced by the same peptides in each group, defining at least five distinctive epitopes within core (amino acids [aa] of 20-44, aa 39-63, aa 79-103, aa 118-152 and aa 148-172) and three regions within E1(aa 198-252, aa 308-372, and aa 368-392). Subjects with strong T-cell responses had low or no detectable levels of peptide-specific antibodies, and vice versa. In particular, T-cell responses were more common in group A; B-cell responses were more common in group B. From our data, we conclude that a benign course of HCV infection may be the consequence of the effective activation of T-helper lymphocytes.
Characterization of Cell Lines Carrying Self-Replicating Hepatitis C Virus RNAs (2001)

Subgenomic selectable RNAs of the hepatitis C virus (HCV) have recently been shown to self-replicate to high levels in the human hepatoma cell line Huh-7 (V. Lohmann, F. Körner, J. O. Koch, U. Herian, L. Theilmann, and R. Bartenschlager, Science 285:110-113, 1999). Taking advantage of this cell culture system that allows analyses of the interplay between HCV replication and the host cell, in this study we characterized two replicon-harboring cell lines that have been cultivated for more than 1 year. During this time, we observed no signs of cytopathogenicity such as reduction of growth rates or ultrastructural changes. High levels of HCV RNAs were preserved in cells passaged under continuous selection. When selective pressure was omitted replicon levels dropped, but depending on culture conditions the RNAs persisted for more than 10 months. A tight coupling of the amounts of HCV RNA and proteins to host cell growth was observed. Highest levels were found in exponentially growing cells, followed by a sharp decline in resting cells, suggesting that cellular factors required for RNA replication and/or translation vary in abundance and become limiting in resting cells. Studies of polyprotein processing revealed rapid cleavages at the NS3/4A and NS5A/B sites resulting in a rather stable NS4AB5A precursor that was processed slowly into individual products. Half-lives (t(1/2)s) of mature proteins ranged from 10 to 16 h, with the exception of the hyperphosphorylated form of NS5A, which was less stable (t(1/2), approximately 7 h). Results of immunoelectron microscopy revealed an association of the majority of viral proteins with membranes of the endoplasmic reticulum, suggesting that this is the site of RNA replication. In summary, replicon-bearing cells are a good model for viral persistence, and they allow the study of various aspects of the HCV life cycle.
Analysis of the Adult Human Plasma Metabolome (2008)

Our nontargeted analytical approach detected a large number of metabolites, including those that were found to be statistically altered with age, sex or race. Age-associated changes were more pronounced than those related to differences in sex or race in the population group we studied. Age, sex and race can be confounding factors when comparing different groups in clinical studies. Future studies to determine the influence of diet, lifestyle and medication are also warranted.
Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patients with rheumatoid arthritis (1999)

These results indicated that fibroblast-like synoviocytes are an important source of the cytokines with IL-2-like activity, IL-15 and IL-7, in RA joints, and that IL-15 may be mainly responsible for local T cell activation and expansion in the presence of deficient IL-2 production by T cells.
Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer (2009)

TP53 mutation occurs in 50-75% of human pancreatic ductal adenocarcinomas (PDAC) following an initiating activating mutation in the KRAS gene. These p53 mutations frequently result in expression of a stable protein, p53(R175H), rather than complete loss of protein expression. In this study we elucidate the functions of mutant p53 (Trp53(R172H)), compared to knockout p53 (Trp53(fl)), in a mouse model of PDAC. First we find that although Kras(G12D) is one of the major oncogenic drivers of PDAC, most Kras(G12D)-expressing pancreatic cells are selectively lost from the tissue, and those that remain form premalignant lesions. Loss, or mutation, of Trp53 allows retention of the Kras(G12D)-expressing cells and drives rapid progression of these premalignant lesions to PDAC. This progression is consistent with failed growth arrest and/or senescence of premalignant lesions, since a mutant of p53, p53(R172P), which can still induce p21 and cell cycle arrest, is resistant to PDAC formation. Second, we find that despite similar kinetics of primary tumor formation, mutant p53(R172H), as compared with genetic loss of p53, specifically promotes metastasis. Moreover, only mutant p53(R172H)-expressing tumor cells exhibit invasive activity in an in vitro assay. Importantly, in human PDAC, p53 accumulation significantly correlates with lymph node metastasis. In summary, by using 'knock-in' mutations of Trp53 we have identified two critical acquired functions of a stably expressed mutant form of p53 that drive PDAC; first, an escape from Kras(G12D)-induced senescence/growth arrest and second, the promotion of metastasis.
Cytoskeletal Regulation by the Nedd8 Ubiquitin-Like Protein Modification Pathway (2002)

The Nedd8 ubiquitin-like protein modification pathway regulates cell-cycle progression. Our analysis of Nedd8 requirements during Caenorhabditis elegans embryogenesis indicates that the cytoskeleton is another target. Nedd8 conjugation negatively regulated contractility of the microfilament-rich cell cortex during pronuclear migration and again during cytokinesis. The Nedd8 pathway also was required after meiosis to negatively regulate katanin, a microtubule-severing complex, permitting the assembly of a large mitotic spindle. We propose that Nedd8-modified cullin, as part of an E3 ubiquitin ligase complex, targets katanin for degradation during the transition from meiosis to mitosis.
Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells (1996)

Human natural killer (NK) cells are bone marrow (BM)-derived CD2+CD16+CD56+ large granular lymphocytes (LGL) that lack CD3 yet contain the T-cell receptor zeta-chain (zeta-TCR). NK cells provide requisite interferon-gamma (IFN-gamma) during the early stages of infection in several experimental animal models. A number of studies have shown that human CD3-CD56+ NK cells can be obtained from BM-derived CD34+ hematopoietic progenitor cells (HPCs) cultured in the presence of interleukin-2 (IL-2) and an allogeneic feeder cell layer, or IL-2 and other hematopoietic growth factors such as the c-kit ligand (KL). The failure to detect the IL-2 gene product within the BM stroma and the presence of NK cells in IL-2-deficient mice suggested that cytokines other than IL-2 may participate in NK cell differentiation from HPCs in vivo. IL-15 is a cytokine which, while lacking any sequence homology in IL-2, can activate cells via the IL-2 receptor. Here we show that human BM stromal cells express the IL-15 transcript, and supernatants from long-term BM stromal cell cultures contain IL-15 protein. In vitro, CD3-CD56+ NK cells can be obtained from 21-day cultures of CD34+ HPCs supplemented with IL-15 in the absence of IL-2, stromal cells, or other cytokines. The addition of the KL to these cultures had no effect on the differentiation of the CD3-CD56+ cytotoxic effector cells, but greatly enhanced their expansion. The majority of these cells lack CD2 and CD16, but do express zeta-TCR. Similar to NK cells found in peripheral blood, the CD2-CD16-CD56+ NK cells grown in the presence of IL-15 were found to be potent producers of IFN-gamma in response to monocyte-derived cytokines. Thus IL-15, like KL, appears to be produced by BM stromal cells. IL-15 can induce CD34+ HPCs to differentiate into CD3-CD56+ NK cells, and KL can amplify this. Therefore, IL-15 may be a physiologically relevant ligand for NK cell differentiation in vivo.
A Survey on Visual Surveillance of Object Motion and Behaviors (2004)

Visual surveillance in dynamic scenes, especially for humans and vehicles, is currently one of the most active research topics in computer vision. It has a wide spectrum of promising applications, including access control in special areas, human identification at a distance, crowd flux statistics and congestion analysis, detection of anomalous behaviors, and interactive surveillance using multiple cameras, etc. In general, the processing framework of visual surveillance in dynamic scenes includes the following stages: modeling of environments, detection of motion, classification of moving objects, tracking, understanding and description of behaviors, human identification, and fusion of data from multiple cameras. We review recent developments and general strategies of all these stages. Finally, we analyze possible research directions, e.g., occlusion handling, a combination of twoand three-dimensional tracking, a combination of motion analysis and biometrics, anomaly detection and behavior prediction, content-based retrieval of surveillance videos, behavior understanding and natural language description, fusion of information from multiple sensors, and remote surveillance.
STRUCTURE AND BIOGENESIS OF THE CELL WALLS OF GRASSES (1996)

The chemical structures of the primary cell walls of the grasses and their progenitors differ from those of all other flowering plant species. They vary in the complex glycans that interlace and cross-link the cellulose microfibrils to form a strong framework, in the nature of the gel matrix surrounding this framework, and in the types of aromatic substances and structural proteins that covalently cross-link the primary and secondary walls and lock cells into shape. This review focuses on the chemistry of the unique polysaccharides, aromatic substances, and proteins of the grasses and how these structural elements are synthesized and assembled into dynamic and functional cell walls. Despite wide differences in wall composition, the developmental physiology of grasses is similar to that of all flowering plants. Grass cells respond similarly to environmental cues and growth regulators, exhibit the same alterations in physical properties of the wall to allow cell growth, and possess similar patterns of wall biogenesis during the development of specific cell and tissue types. Possible unifying mechanisms of growth are suggested to explain how grasses perform the same wall functions as other plants but with different constituents and architecture.
Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 – continuity and change (2019)

The new 2017 revisions will simplify the application of the MRI criteria for dissemination in space and include CSF findings as evidence for dissemination in time in clinically isolated syndrome.
JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis (2007)

Abstract Few investigators have evaluated the usefulness of the JAK2 V617F mutation for explaining the phenotypic variations and for predicting the risk of major clinical events in primary myelofibrosis (PMF). In a transversal survey we assayed by allele-specific polymerase chain reaction (PCR) the JAK2 V617F mutational status in 304 patients with PMF. Multiple DNA samples were collected prospectively from 64 patients, and a highly sensitive quantitative PCR was used as a confirmatory test. In a longitudinal prospective study we determined the progression rate to clinically relevant outcomes in 174 patients who had JAK2 mutation determined at diagnosis. JAK2 V617F was identified in 63.4% of patients. None of the V617F-negative patients who were sequentially genotyped progressed to become V617F positive, whereas progression rate from heterozygous to homozygous mutation was 10 per 100 patient-years. JAK2 V617F mutation contributed to hemoglobin, aquagenic pruritus, and platelet count variability, whereas homozygous mutation was independently associated with higher white blood cell count, larger spleen size, and greater need for cytoreductive therapies. Adjusting for conventional risk factors, V617F mutation independently predicted the evolution toward large splenomegaly, need of splenectomy, and leukemic transformation. We conclude that JAK2 V617F genotype should be considered in any future risk stratification of patients with PMF.
High‐density seeding of myocyte cells for cardiac tissue engineering (2003)

Tissue engineering of 1- to 5-mm-thick, functional constructs based on cells that cannot tolerate hypoxia for prolonged time periods (e.g., cardiac myocytes) critically depends on our ability to seed the cells at a high and spatially uniform initial density and to maintain their viability and function. We hypothesized that rapid gel-cell inoculation in conjunction with direct medium perfusion through the seeded scaffold would increase the rate, yield, viability, and uniformity of cell seeding. Two cell types were studied: neonatal rat cardiomyocytes for feasibility studies of seeding and cultivation with direct medium perfusion, and C2C12 cells (a murine myoblast cell line) for detailed seeding studies. Cells were seeded at densities corresponding to those normally present in the adult rat heart ([0.5-1] x 10(8) cells/cm(3)), into collagen sponges (13 mm x 3 mm discs), using Matrigel as a vehicle for rapid cell delivery. Scaffolds inoculated with cell-gel suspension were seeded either in perfused cartridges with alternating medium flow or in orbitally mixed Petri dishes. The effects of seeding time (1.5 or 4.5 h), initial cell number (6 or 12 million cells per scaffold), and seeding set-up (medium perfusion at 0.5 and 1.5 mL/min; orbitally mixed dishes) were investigated using a randomized three-factor factorial experimental design with two or three levels and three replicates. The seeding cell yield was consistently high (over 80%), and it appeared to be determined by the rapid gel inoculation. The decrease in cell viability was markedly lower for perfused cartridges than for orbitally mixed dishes (e.g., 8.8 +/- 0.8% and 56.3 +/- 4%, respectively, for 12 million cells at 4.5 h post-seeding). Spatially uniform cell distributions were observed in perfused constructs, whereas cells were mainly located within a thin (100-200 microm) surface layer in dish seeded constructs. Over 7 days of cultivation, medium perfusion maintained the viability and differentiated function of cardiac myocytes, and the constructs contracted synchronously in response to electrical stimulation. Direct perfusion can thus enable seeding of hypoxia-sensitive cells at physiologically high and spatially uniform initial densities and maintain cell viability and function.
Baseline Susceptibility of Primary Human Immunodeficiency Virus Type 1 to Entry Inhibitors (2002)

Human immunodeficiency virus type 1 plasma viruses from 29 entry inhibitor-naive patients were characterized for their susceptibilities to T-20, AMD3100, and RANTES. A strikingly wide range of susceptibilities to T-20 was observed that was influenced by coreceptor usage but not by the susceptibilities of the viruses to inhibitors that target the chemokine receptors or by polymorphisms in the gp41 N helix.
A novel human CD32 mAb blocks experimental immune haemolytic anaemia in FcγRIIA transgenic mice (2005)

A fully human IgG1 kappa antibody (MDE-8) was generated, which recognised Fc-gamma receptor IIa (FcgammaRIIa) molecules on CD32 transfectants, peripheral blood monocytes, polymorphonuclear cells and platelets. This antibody blocked FcgammaRIIa ligand-binding via its F(ab')(2) fragment. Overnight incubation of monocytes with F(ab')(2) fragments of MDE-8 leads to a c. 60% decrease in cell surface expression of FcgammaRIIa. MDE-8 whole antibody induced a concomitant c. 30% decrease of FcgammaRI on THP-1 cells and monocytes. In humans FcgammaRIIa plays an important role in the clearance of antibody-coated red blood cells in vivo. As an equivalent of FcgammaRIIa does not exist in mice, the in vivo effect of MDE-8 was studied in an FcgammaRIIa transgenic mouse model. In these mice, antibody-induced anaemia could readily be blocked by MDE-8. These data document a new human antibody that effectively blocks FcgammaRIIa, induces modulation of both FcgammaRIIa and FcgammaRI from phagocytic cells, and ameliorates antibody-induced anaemia in vivo.
Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells modulation of Fas/Fas ligand and caspase-3 pathway (2000)

Epinephrine induces apoptosis in HCAECs, and this effect is associated with activation of Fas-FasL and caspase-3 signal transduction pathway. Carvedilol can, more effectively than atenolol, inhibit these effects of epinephrine. The potent antioxidant effect of carvedilol is probably responsible for the superior effect.
Model for l/f Flux Noise in SQUIDs and Qubits (2007)

We propose a model for 1/f flux noise in superconducting devices (f is frequency). The noise is generated by the magnetic moments of electrons in defect states which they occupy for a wide distribution of times before escaping. A trapped electron occupies one of the two Kramers-degenerate ground states, between which the transition rate is negligible at low temperature. As a result, the magnetic moment orientation is locked. Simulations of the noise produced by randomly oriented defects with a density of 5*10^17 m^-2 yield 1/f noise magnitudes in good agreement with experiments.
Pathogenesis of atherosclerosis. (1994)

Two recent developments provide strong support for the role of plasma lipoproteins in plaque formation: plaque stabilization due to rapid removal of cholesterol from macrophage-foam cells has been suggested to explain the rapid cessation of clinical coronary artery disease events after aggressive lipoprotein-modifying therapy; and transgenic mice studies using overexpression and gene knockout of apolipoproteins A-I and E suggest that remnant lipoprotein particles are atherogenic and that apolipoprotein A-I (high-density lipoprotein) can clearly inhibit atherosclerosis development. Two of the more exciting areas of vascular-wall biology at this time are the possibility that endothelial dysfunction may be assessed by measurement of circulating factors (such as atherosclerosis-associated endothelial leukocyte adhesion molecule), and studies of the role of fibrin-like peptides in atherogenesis and coronary artery disease risk assessment.
A Sequential Algorithm for Possibility-Based Design Optimization (2007)

Deterministic optimal designs that are obtained without taking into account uncertainty/variation are usually unreliable. Although reliability-based design optimization accounts for variation, it assumes that statistical information is available in the form of fully defined probabilistic distributions. This is not true for a variety of engineering problems where uncertainty is usually given in terms of interval ranges. In this case, interval analysis or possibility theory can be used instead of probability theory. This paper shows how possibility theory can be used in design and presents a computationally efficient sequential optimization algorithm. After the fundamentals of possibility theory and fuzzy measures are described, a double-loop, possibility-based design optimization algorithm is presented where all design constraints are expressed possibilistically. The algorithm handles problems with only uncertain or a combination of random and uncertain design variables and parameters. In order to reduce the high computational cost, a sequential algorithm for possibility-based design optimization is presented. It consists of a sequence of cycles composed of a deterministic design optimization followed by a set of worst-case reliability evaluation loops. Two examples demonstrate the accuracy and efficiency of the proposed sequential algorithm.
Empirical study based on machine learning approach to assess the QoS/QoE correlation (2012)

The appearance of new emerging multimedia services have created new challenges for cloud service providers, which have to react quickly to end-users experience and offer a better Quality of Service (QoS). Cloud service providers should use such an intelligent system that can classify, analyze, and adapt to the collected information in an efficient way to satisfy end-users' experience. This paper investigates how different factors contributing the Quality of Experience (QoE), in the context of video streaming delivery over cloud networks. Important parameters which influence the QoE are: network parameters, characteristics of videos, terminal characteristics and types of users' profiles. We describe different methods that are often used to collect QoE datasets in the form of a Mean Opinion Score (MOS). Machine Learning (ML) methods are then used to classify a preliminary QoE dataset collected using these methods. We evaluate six classifiers and determine the most suitable one for the task of QoS/QoE correlation.
Mucosal Biofilm Formation on Middle‐Ear Mucosa in a Nonhuman Primate Model of Chronic Suppurative Otitis Media (2005)

P. aeruginosa forms biofilms in the middle ear in CSOM in primates. To our knowledge, this is the first report of disease-associated bacterial biofilm in a nonhuman primate model of CSOM. Such a model lays a foundation for much needed study into the role of biofilms in the pathophysiology of CSOM. Should CSOM be caused by biofilms, which is uncertain at this time, development of novel strategies for treatment and prevention may be possible. The finding of both rods and cocci forming biofilms also warrants further investigation.