gebhart/patrepeval huggingface dataset:
Gamma interferon and lymphotoxin, released by activated T cells, synergize to inhibit granulocyte/monocyte colony formation. (1986)

We have shown that lymphocytes stimulated by PHA produce colony-forming unit of granulocyte/monocyte (CFU-GM)-stimulating and -inhibiting activities, IFN-gamma, and lymphotoxin (LT). IFN-gamma is necessary for inhibition of CFU-GM by PHA-conditioned medium (CM), as shown by experiments in which removal of IFN-gamma from PHA-CM abrogated inhibition. However, experiments in which rIFN-gamma was added to IFN-gamma-depleted PHA-CM revealed the presence, in PHA-CM, of other factors that act in synergy with IFN-gamma to inhibit CFU-GM. Fractionation of PHA-CM on a Sephadex G-100 column was used to separate IFN-gamma and LT. Colony-inhibiting activity was eluted in fractions that contained both IFN-gamma and LT activities, identifying LT as a factor present in PHA-CM that synergizes with IFN-gamma to inhibit CFU-GM. Treatment of PHA-CM with mAb against either IFN-gamma or LT completely abrogated the colony-inhibiting activity, demonstrating a requirement for both lymphokines in PHA-CM-induced inhibition of CFU-GM. Experiments using rIFN-gamma and preparations of purified LT confirmed that neither lymphokine alone, when added to bone marrow cells at the concentrations present in PHA-CM, strongly inhibited day 7 or day 14 CFU-GM, but that the two lymphokines, added together, behaved synergistically to inhibit CFU-GM by up to 70%. The inhibition observed using purified preparations of lymphokines shows that synergy between IFN-gamma and LT is sufficient to explain PHA-CM-induced inhibition of CFU-GM. Our findings suggest that activated T cells regulate hematopoiesis through the release of inhibitory as well as stimulatory factors, and that the simultaneous production of IFN-gamma and LT may represent a mechanism of suppression of hematopoiesis in the cases of bone marrow failure associated with the presence of activated T cells.
Rare Mutations of the PIK3CA Gene in Hematologic Malignancies. (2004)

Abstract Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that is activated in advanced cancers through inactivation of the PTEN tumor suppressor gene. Somatic mutations in the p110-alpha catalytic subunit, PIK3CA occur in colon, gastric, breast and lung cancers as well as in glioblastomas and colorectal adenomas. Mutations were found in two “hot spots”: the helical (exon 9) and kinase (exon 20) domains. Mutational analysis of PIK3CA in hematologic malignancies has not been reported. We performed a screening analysis of 28 cell lines from human hematologic malignancies as well as 46 AML and MDS samples and 42 lymphoma samples by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and nucleotide sequencing of the two “hot spots”. Two colon adenocarcinoma cell lines (SKCol1, SW403) were used as positive controls and revealed the known missense mutation (Q546K) in exon 9. A novel missense mutation occurred in the erythroid chronic myeloid leukemia cell line K562, causing an amino acid change from Glutamic acid to Alanine at amino acid position 545 of exon 9 (E545A). In the kinase domain (exon 20), a novel polymorphism was observed in two different MDS patients at Threonine residue 1025. Experiments are exploring the functional importance of the PIK3CA mutation and the PIK3CA polymorphism in exon 20. In summary, PIK3CA mutations are infrequent in hematologic malignancies.
High Current Focused Ion Beam Instrument for Destructive Physical Analysis Applications (2008)

Abstract Conventional focused ion beams (FIB) employing liquid metal ion sources (LMIS) are used to create site specific cross-sections for viewing subsurface features and performing 3D metrology on subsurface structure. Emerging applications incorporate novel materials as well as large structures that interface to decreasing IC dimensions and often require destructive physical analysis. This paper describes a novel instrument in which an inductively coupled plasma ion source is integrated onto a conventional FIB column. It compares this instrument to the existing LMIS FIBs and shows examples that illustrate the capabilities of this tool. This instrument retains the benefits of the conventional LMIS FIB such as high placement accuracy and the ability to immediately obtain high resolution images of the cross-section face without having to transfer it to another tool. It is capable of creating large cross-sections from 10 microns to 1mm in size at about 100 times faster than a conventional FIB.
RU486, A Progestin and Glucocorticoid Antagonist, Inhibits the Growth of Breast Cancer Cells via the Progesterone Receptor* (1985)

The progestin and glucocorticoid antagonist RU486 was tested on the growth of several cell lines in culture. RU486 inhibited the growth of two progesterone receptor (RP) positive human breast cancer cell lines (MCF7 and T47D). The antiproliferative effect was dose dependent and its magnitude correlated with the RP content of the tested cells (T47D greater than estradiol-primed MCF7 greater than withdrawn MCF7). Cell growth inhibition was not prevented by the addition of dexamethasone, dihydrotestosterone, or estradiol, but the cells were rescued by low concentrations of the progestin R5020. RU486 had no effect on the growth of two RP negative human breast cancer cell lines and a rat fibroblast cell line. Moreover, RU486 had no progestin agonist activity in T47D cells when evaluated by measuring the 35S-labeling of two progestin-regulated proteins with mol wts of 48,000 and 250,000, but it totally prevented the induction of these two proteins by R5020. In conclusion, RU486 selectively inhibited the growth of human breast cancer cell lines with unoccupied RP sites and its effect was correlated with the RP concentration of these cells. We propose that RU486 is a RP-targeted drug of potential utility in breast cancer treatment.
High-Throughput Massively Parallel Sequencing for Fetal Aneuploidy Detection from Maternal Plasma (2013)

These data suggest that the developed laboratory methods in concert with improved bioinformatic approaches enable higher sample throughput while maintaining high classification accuracy.
Text Entry for Mobile Computing: Models and Methods, Theory and Practice (2002)

Text input for mobile or handheld devices is a flourishing research area. This article begins with a brief history of the emergence and impact of mobile computers and mobile communications devices. Key factors in conducting sound evaluations of new technologies for mobile text entry are presented, including methodology and experiment design. Important factors to consider are identified and elaborated, such as focus of attention, text creation versus text copy tasks, novice versus expert performance, quantitative versus qualitative measures, and the speed-accuracy trade-off. An exciting area within mobile text entry is the combined use of Fitts' law and a language corpus to model, and subsequently optimize, a text entry technique. The model is described, along with examples for a variety of soft keyboards as well as the telephone keypad. A survey of mobile text entry techniques, both in research papers and in commercial products, is presented.
Identification and Mutagenesis of the Adeno-Associated Virus 5 Sialic Acid Binding Region (2014)

Despite the fact that a majority of AAVs utilize sialic acid for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, the sialic acid binding regions of AAV5 were identified and studied using a variety of approaches. Mutagenesis of this region resulted in elimination or alteration in sialic acid-dependent transduction in cell lines. This change in sialic acid glycan binding was confirmed using glycan arrays. Further study also demonstrated a change in transduction and activity and cell tropism in vivo as well as resistance to neutralization by antibodies raised against the wild-type virus.
Personnel Preparation and Service Delivery Issues in Rural Areas: The State of the Art (2002)

Preparation of high quality personnel to provide educational services to students with disabilities living in rural areas is, at best, challenging. Findings from a comprehensive study concerning the status of the implementation of the Individuals with Disabilities Education Act (IDEA) in rural settings and the issues such implementation presents to teacher education programs in these areas are discussed. Members of the American Council on Rural Special Education (ACRES) participated in the study. Results indicated that strategies for enhancing personnel preparation, recruitment, and retention of individuals to institutions of higher education and K-12 schools in rural settings include distance learning, on-site professional development opportunities, salary incentives/increments, and benefits. Linking evaluation data to the general education curriculum and determining how the student's disabilities affect his/her progress in general education are issues for practitioners implementing IDEA in rural settings. Recommendations are provided for enhancing personnel preparation and service delivery based on the results.
Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer (2005)

The CD1d reactive glycolipid, alpha-galactosylceramide (alpha-GalCer), potently activates T cell receptor-alpha type I invariant NKT cells that secondarily stimulate the proliferation and activation of other leukocytes, including NK cells. Here we report a rational approach to improving the antitumor activity of alpha-GalCer by using delayed interleukin (IL)-21 treatment to mature the alpha-GalCer-expanded pool of NK cells into highly cytotoxic effector cells. In a series of experimental and spontaneous metastases models in mice, we demonstrate far superior antitumor activity of the alpha-GalCer/IL-21 combination above either agent alone. Superior antitumor activity was critically dependent upon the increased perforin-mediated cytolytic activity of NK cells. Transfer of alpha-GalCer-pulsed dendritic cells (DCs) followed by systemic IL-21 caused an even more significant reduction in established (day 8) metastatic burden and prolonged survival. In addition, this combination prevented chemical carcinogenesis more effectively. Combinations of IL-21 with other NK cell-activating cytokines, such as IL-2 and IL-12, were much less effective in the same experimental metastases models, and these cytokines did not substitute effectively for IL-21 in combination with alpha-GalCer. Overall, the data suggest that NK cell antitumor function can be enhanced greatly by strategies that are designed to expand and differentiate NK cells via DC activation of NKT cells.
Immunolocalization of estrogen receptor alpha and beta in gastric epithelium and enteric neurons (2001)

A sexual dimorphism in gastric acid secretion has been known for many years, with women secreting less acid ( approximately 40%) than men. The mechanisms mediating this sex difference are unknown, but a role for estrogens is suggested from animal models. Two estrogen receptor (ER) subtypes, ER alpha and ER beta, mediate genomic effects of estrogens, and mRNA for both subtypes has been detected in the rat stomach. The objective of this study was to determine the cellular distribution of ER alpha and ER beta proteins in the rat stomach. ER alpha and ER beta proteins were detected in nuclei of fundic parietal cells and epithelial cells in the progenitor zone. In the antrum, several cells were immunoreactive for ER beta in regions containing stem and neuroendocrine cell types but ER alpha protein was not detected in antral glands. Both ER alpha and ER beta proteins were expressed in enteric neurons within the nucleus and cytoplasm, with specific punctate staining for ER alpha in cell bodies and fibers. These studies are the first to show differences between ER alpha and ER beta proteins in the epithelial cellular distribution in the fundus and antrum and to detect co-expression in enteric neurons. These results suggest that estrogens may inhibit gastric acid secretion via genomic effects in fundic parietal cells through either ER subtype and in antral neuroendocrine cells via ER beta. Moreover, co-expression of ER alpha and ER beta in enteric neurons indicates that estrogenic effects could also be mediated through neurogenic reflexes. Our findings imply that direct regulation of multiple cell types by estrogens may contribute to the modulation of gastric functions that have been recognized during the estrous cycle and between the sexes.
The European Equity Markets: The State of the Union and an Agenda for the Millennium (1996)

This comprehensive and unprecedented book investigates the barriers to European equity market integration which will remain after 1996. It represents the culmination of a major international research effort, sponsored by the European Capital Markets Institute. Written by a group of renowned specialists, under the direction of Benn Steil, this book will illuminate the workings of the European equity markets and shape the public policy agenda for the coming millennium. The authors provide in-depth and original analyses of European equity trading, institutional investment, market regulation, corporate governance, pension funds, capital standards, accounting issues, clearance and settlement, and the European single currency. Market practitioners, policymakers, regulators, researchers, and students will find it an invaluable guide to the most dynamic sector of the European single market. In addition to Benn Steil, the authors are Erik Berglof, Frederick Choi, Richard Dale, E. Philip Davis, Jeffrey Frankel, Ian Giddy, Richard Levich, Marco Pagano, Anthony Saunders, Robert Schwartz, Ingo Walter, and Simon Wolfe.
Synthesis of 5H‐pyrazolo[5,1‐c][1,4]benzodiazepine (1983)

Abstract The reaction of 2‐nitrobenzyl bromide with dimethyl pyrazole‐3, 5‐dicarboxylate gave dimethyl 1‐(2‐nitrobenzyl)pyrazole‐3, 5‐dicarboxylate which through a few steps procedure afforded the key intermediate 5, 10‐dihydro‐11‐oxopyrazolo[5, 1‐ c ][l, 4]benzodiazepine. The latter was reduced and dehydrogenated to yield the new tricyclic system 5 H ‐pyrazolo[5, 1‐ c ][1, 4]benzodiazepine.
Polyphosphate modulates blood coagulation and fibrinolysis (2006)

Inorganic polyphosphate is an abundant component of acidocalcisomes of bacteria and unicellular eukaryotes. Human platelet dense granules strongly resemble acidocalcisomes, and we recently showed that they contain substantial amounts of polyphosphate, which is secreted upon platelet activation. We now report that polyphosphate is a potent hemostatic regulator, accelerating blood clotting by activating the contact pathway and promoting the activation of factor V, which in turn results in abrogation of the function of the natural anticoagulant protein, tissue factor pathway inhibitor. Polyphosphate was also found to delay clot lysis by enhancing a natural antifibrinolytic agent, thrombin-activatable fibrinolysis inhibitor. Polyphosphate is unstable in blood or plasma, owing to the presence of phosphatases. We propose that polyphosphate released from platelets or microorganisms initially promotes clot formation and stability; subsequent degradation of polyphosphate by blood phosphatases fosters inhibition of clotting and activation of fibrinolysis during wound healing.
A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein (2007)

G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein (rHDL) phospholipid bilayer particle together with the stimulatory heterotrimeric G protein, Gs. Single-molecule fluorescence imaging and FRET analysis demonstrate that a single beta2AR is incorporated per rHDL particle. The monomeric beta2AR efficiently activates Gs and displays GTP-sensitive allosteric ligand-binding properties. These data suggest that a monomeric receptor in a lipid bilayer is the minimal functional unit necessary for signaling, and that the cooperativity of agonist binding is due to G protein association with a receptor monomer and not receptor oligomerization.
Gleevec Increases Levels of the Amyloid Precursor Protein Intracellular Domain and of the Amyloid-β–degrading Enzyme Neprilysin (2007)

Amyloid-beta (Abeta) deposition is a major pathological hallmark of Alzheimer's disease. Gleevec, a known tyrosine kinase inhibitor, has been shown to lower Abeta secretion, and it is considered a potential basis for novel therapies for Alzheimer's disease. Here, we show that Gleevec decreases Abeta levels without the inhibition of Notch cleavage by a mechanism distinct from gamma-secretase inhibition. Gleevec does not influence gamma-secretase activity in vitro; however, treatment of cell lines leads to a dose-dependent increase in the amyloid precursor protein intracellular domain (AICD), whereas secreted Abeta is decreased. This effect is observed even in presence of a potent gamma-secretase inhibitor, suggesting that Gleevec does not activate AICD generation but instead may slow down AICD turnover. Concomitant with the increase in AICD, Gleevec leads to elevated mRNA and protein levels of the Abeta-degrading enzyme neprilysin, a potential target gene of AICD-regulated transcription. Thus, the Gleevec mediated-increase in neprilysin expression may involve enhanced AICD signaling. The finding that Gleevec elevates neprilysin levels suggests that its Abeta-lowering effect may be caused by increased Abeta-degradation.
A Recombinant Chimeric Epidermal Growth Factor-like Module with High Binding Affinity for Integrins (2003)

Integrins are cell surface receptors involved in numerous pathological processes such as metastasis invasion and abnormal angiogenesis. To target these receptors, the epidermal growth factor (EGF)-like domain of human complement protease C1r was used as a natural scaffold to design chimeric modules containing the RGD motif. Here we report a high yield bacterial expression system and its application to the production of two such modules, EGF-RGD and V2, the latter variant mimicking the RGD-containing domain of disintegrins. These modules were characterized chemically, and their biological activity was investigated by cellular assays using various Chinese hamster ovary cell lines expressing beta1 and beta3 integrins and by surface plasmon resonance spectroscopy. Remarkably, the modifications leading to the V2 variant had differential effects on the interaction with beta3 and beta1 integrins. The disintegrin-like V2 module exhibited enhanced binding affinities compared with EGF-RGD, with KD values of 7.2 nm for alpha5beta1 (a 4-fold decrease) and 3.5 nm for alphavbeta3 (a 1.5-fold decrease), comparable with the values determined for natural integrin ligands. Analysis by NMR spectroscopy also revealed a differential dynamic behavior of the RGD motif in the EGF-RGD and V2 variants, providing insights into the structural basis of their relative binding efficiency. These novel RGD-containing EGF modules open the way to the design of improved variants with selective affinity for particular integrins and their use as carriers for other biologically active modules.
Treatment of Scleromalacia Perforans With Dura Mater Grafting (1992)

We describe, to our knowledge for the first time in the English literature, the successful use of cadaveric dura mater in reinforcing the sclera in a rheumatoid arthritis patient with scleromalacia perforans.
Towards middleware services for mobile ad-hoc network applications (2004)

Mobile ad-hoc networks are typically very dynamic networks in terms of available communication partners, network resources, connectivity, etc. Furthermore, the end-user devices are very heterogeneous, ranging from high-end laptops to low-end PDAs and mobile phones. Traditionally, middleware is used to abstract from this heterogeneity and to enable the application programmer to focus on application issues. We propose to develop middleware services that additionally provide services for information sharing in mobile ad-hoc networks, because the possibility to share information is mission critical for many mobile ad-hoc network applications.
An algorithm for data-driven bandwidth selection (2003)

The analysis of a feature space that exhibits multiscale patterns often requires kernel estimation techniques with locally adaptive bandwidths, such as the variable-bandwidth mean shift. Proper selection of the kernel bandwidth is, however, a critical step for superior space analysis and partitioning. This paper presents a mean shift-based approach for local bandwidth selection in the multimodal, multivariate case. The method is based on a fundamental property of normal distributions regarding the bias of the normalized density gradient. This paper demonstrates that, within the large sample approximation, the local covariance is estimated by the matrix that maximizes the magnitude of the normalized mean shift vector. Using this property, the paper develops a reliable algorithm which takes into account the stability of local bandwidth estimates across scales. The validity of the theoretical results is proven in various space partitioning experiments involving the variable-bandwidth mean shift.
C/EBPbeta is over‐expressed in gastric carcinogenesis and is associated with COX‐2 expression (2006)

The CCAAT/enhancer-binding protein beta (C/EBPbeta) transcription factor has been associated with several cancer models. In this study, the expression of C/EBPbeta was analysed in a series of 90 gastric carcinomas (GCs). We also assessed the effect of C/EBPbeta on COX-2 expression. In normal gastric mucosa, C/EBPbeta expression was restricted to cells in the proliferative zone. In intestinal metaplasia, dysplasia, and GC of the intestinal and atypical subtypes, C/EBPbeta was over-expressed (p < 0.0001, for the association with histological type). C/EBPbeta and Ki67, a marker of cell proliferation, were also co-expressed in primary GC. We also observed an overlap between C/EBPbeta and COX-2 expression in GC. Using GC cell lines we show that C/EBPbeta can regulate the expression of endogenous COX-2 and transactivate the promoter of the COX-2 gene, depending on its methylation status. These results suggest that C/EBPbeta may be a marker of neoplastic transformation and also play an active role in gastric tumourigenesis by regulating COX-2 expression.
The effects of predicated execution on branch prediction (1994)

High performance architectures have always had to deal with the performance limiting impact of branch operations. Microprocessor designs are going to have to deal with this problem as well, as they move towards deeper pipelines and support for multiple instruction issue. Branch prediction schemes are often used to alleviate the negative impact of branch operations by allowing the speculative execution of instructions after an unresolved branch. Another technique is to eliminate branch instructions altogether. Predication can remove forward branch instructions by translating the instructions following the branch into predicate form.