gebhart/patrepeval huggingface dataset:
Natural glucocorticoids induce expansion of all developmental stages of murine bone marrow granulocytes without inhibiting function (2008)

Natural glucocorticoids (Gc) produced during stress have profound effects on the immune system. It is well known that Gc induce apoptosis in precursor T and B cells, markedly altering lymphopoiesis. However, it has been noted that marrow myeloid cells expanded both in proportion and absolute numbers in the mouse after Gc exposure. Mice were implanted with a corticosterone (CS) tablet that increased serum Gc and caused atrophied thymuses, both classic signs of activation of the stress axis. Blood neutrophil counts were elevated (4.8x), whereas lymphocyte counts declined. Flow cytometric analysis of the marrow revealed that the phenotypic distribution of the various major classes of cells was shifted by Gc exposure. As expected, marrow lymphocyte numbers declined >40% after 3 days of exposure to Gc. Conversely, in the myeloid compartment, both monocytes and granulocytes increased in number by >40%. Further, all granulocyte developmental stages showed large increases in both total number and percentage of cells. To investigate the functional capacity of mature granulocytes from Gc-treated mice, an improved granulocyte isolation method was developed. Gc exposure had little effect on the ability of granulocytes to produce superoxide or undergo chemotaxis or phagocytose bacteria. These results indicate that Gc treatment shifts bone marrow composition and provides evidence that granulocytes and their progenitors are selectively preserved under stressful conditions without losing function.
Evidence for Neuroprotective Effects of Endogenous Brain-Derived Neurotrophic Factor after Global Forebrain Ischemia in Rats (1999)

The levels of brain-derived neurotrophic factor (BDNF) vary between different forebrain areas and show region-specific changes after cerebral ischemia. The present study explores the possibility that the levels of endogenous BDNF determine the susceptibility to ischemic neuronal death. To block BDNF activity the authors used the TrkB-Fc fusion protein, which was infused intraventricularly in rats during 1 week before and 1 week after 5 or 30 minutes of global forebrain ischemia. Ischemic damage was quantified in the striatum and hippocampal formation after 1 week of reperfusion using immunocytochemistry and stereological procedures. After the 30-minute insult, there was a significantly lower number of surviving CA4 pyramidal neurons, neuropeptide Y-immunoreactive dentate hilar neurons, and choline acetyltransferase- and TrkA-positive, cholinergic striatal interneurons in the TrkB-Fc-infused rats as compared to controls. In contrast, the TrkB-Fc treatment did not influence survival of CA1 or CA3 pyramidal neurons or striatal projection neurons. Also, after the mild ischemic insult (5 minutes), neuronal death in the CA1 region was similar in the TrkB-Fc-treated and control groups. These results indicate that endogenous BDNF can protect certain neuronal populations against ischemic damage. It is conceivable, though, that efficient neuroprotection after brain insults is dependent not only on this factor but on the concerted action of a large number of neurotrophic molecules.
Transcription Factor Loading on the MMTV Promoter: A Bimodal Mechanism for Promoter Activation (1992)

The mouse mammary tumor virus (MMTV) promoter attains a phased array of six nucleosomes when introduced into rodent cells. This architecture excludes nuclear factor 1/CCAAT transcription factor (NF1/CTF) from the promoter before glucocorticoid treatment and hormone-dependent access of nucleolytic agents to promoter DNA. In contrast, when the promoter was transiently introduced into cells, NF1/CTF was bound constitutively and nucleolytic attack was hormone-independent. Thus, induction at this promoter was a bimodal process involving receptor-dependent remodeling of chromatin that allows NF1/CTF loading and direct receptor-mediated recruitment of additional transcription factors.
High-Frequency Oscillations in the Output Networks of the Hippocampal–Entorhinal Axis of the Freely Behaving Rat (1996)

Population bursts of the CA3 network, which occur during eating, drinking, awake immobility, and slow-wave sleep, produce a large field excitatory postsynaptic potential throughout stratum radiatum of the CA1 field (sharp wave). The CA3 burst sets into motion a short-lived, dynamic interaction between CA1 pyramidal cells and interneurons, the product of which is a 200 Hz oscillatory field potential (ripple) and phase-related discharge of the CA1 network. Although many CA1 pyramidal neurons discharge during the time (50-100 msec) of each sharp wave, each wave of a ripple (approximately 5 msec) reflects the synchronization of more discrete subsets of CA1 neurons. When we used multi-site recordings in freely behaving rats, we observed ripples throughout the longitudinal extent (approximately 4-5 mm) of the dorsal CA1 region that were coherent for multiple cycles of each ripple. High-frequency ripples were also observed throughout the hippocampal-entorhinal output pathway that were concurrent but less coherent on a cycle-by-cycle basis. Single and multiunit neuronal activity was phase-related to local ripples throughout the hippocampal-entorhinal output pathway. Entorhinal ripples occurred 5-30 msec after the CA1 ripples and were related to the occurrence of an entorhinal sharp wave. Thus, during each hippocampal sharp wave, there is powerful synchronization among the neuronal networks that connect the hippocampus to the neocortex. We suggest that this population interaction (1) biologically constrains theoretical models of hippocampal function and dysfunction and (2) has the capacity to support an "off-line" memory consolidation process.
Market impact and trading profile of hidden orders in stock markets (2009)

We empirically study the market impact of trading orders. We are specifically interested in large trading orders that are executed incrementally, which we call hidden orders. These are statistically reconstructed based on information about market member codes using data from the Spanish Stock Market and the London Stock Exchange. We find that market impact is strongly concave, approximately increasing as the square root of order size. Furthermore, as a given order is executed, the impact grows in time according to a power law; after the order is finished, it reverts to a level of about 0.5-0.7 of its value at its peak. We observe that hidden orders are executed at a rate that more or less matches trading in the overall market, except for small deviations at the beginning and end of the order.
Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin αIIbβ3 (2005)

Integrin activation (inside-out signaling) in platelets can be initiated by agonists such as von Willebrand factor (VWF) and thrombin. Here we show that a mitogen-activated protein kinase (MAPK), p38, plays an important role in the activation of integrin alphaIIb beta3 induced by VWF and thrombin. A dominant-negative mutant of p38, p38AF, inhibits alphaIIb beta3 activation induced by VWF binding to its receptor, the platelet glycoprotein Ib-IX (GPIb-IX), and p38 inhibitors diminish platelet aggregation induced by VWF or low-dose thrombin. The inhibitory effect of p38 inhibitor is unlikely to be caused by the previous suggested effect on cyclo-oxygenase, as inhibition also was observed in the presence of high concentrations of cyclo-oxygenase inhibitor, aspirin. VWF or thrombin induces p38 activation, which is inhibited in cGMP-dependent protein kinase (PKG)-knockout mouse platelets and PKG inhibitor-treated human platelets, indicating that activation of p38 is downstream from PKG in the signaling pathway. p38AF or p38 inhibitors diminish PKG-induced phosphorylation of extracellular stimuli-responsive kinase (ERK), which also is important in integrin activation. Thus, p38 plays an important role in mediating PKG-dependent activation of ERK. These data delineate a novel signaling pathway in which platelet agonists sequentially activate PKG, p38, and ERK pathways leading to integrin activation.
Molecular characterization of a human tyrosinase‐related‐protein‐2 cDNA (1994)

Pigmentation in mammals is under complex genetic control. Amongst the genes involved in this process, those encoding tyrosinase and the tyrosinase-related-proteins 1 and 2 have been well characterized and share a number of features. Recently, the murine tyrosinase-related-protein-2 gene was shown to encode dopachrome-tautomerase activity and was mapped to the slaty locus. Human tyrosinase and tyrosinase-related-protein-1 genes have been isolated and demonstrate a high degree of similarity with their murine counterparts. However, there has been limited data regarding the existence of a human homologue for tyrosinase-related-protein-2 and its relationship to the other tyrosinase-related proteins. In this study, we report the molecular isolation of a cDNA encoding a human homologue of the murine tyrosinase-related-protein-2/dopachrome tautomerase. We have characterized its expression in human melanocytic cells and have analyzed the relationship between dopachrome tautomerase and tyrosinase activities with the level of visible pigmentation in these cells. TYRP2 has been mapped to the chromosomal region 13q32, thus extending a region of synteny with mouse-chromosome 14.
Growth of macrophage-tropic and primary human immunodeficiency virus type 1 (HIV-1) isolates in a unique CD4+ T-cell clone (PM1): failure to downregulate CD4 and to interfere with cell-line-tropic HIV-1 (1995)

Human immunodeficiency virus type 1 (HIV-1) isolates derived directly from clinical samples are usually unable to grow in cytokine-independent continuous cell lines, thus hindering the study of their biological features and their sensitivity to humoral and cellular protective immunity. To overcome these limitations, we have derived from the Hut78 T-cell line a CD4+ clone (PM1) characterized by a unique susceptibility to a wide range of HIV-1 isolates, including primary and biologically pure macrophage (M phi)-tropic isolates (e.g., HIV-1BaL), which are unable to infect other human T- or promonocytic cell lines. Both primary and M phi-tropic HIV-1 establish persistent infection in PM1, with sustained levels of virus replication for prolonged periods. Experiments with chimeric viruses containing envelope fragments of HIV-1BAL inserted into the genetic framework of HXB2, a molecular clone derived from the cell-line-tropic isolate HIV-1IIIB, showed the third hypervariable domain (V3) of gp120 to be a critical determinant of the cell line tropism of HIV-1. Nevertheless, the V3 loop of HIV-1BaL was not sufficient to confer on the chimeras a bona fide M phi tropism. The biological characteristics of HIV-1BaL and of a primary isolate (HIV-1(573)) were investigated by using the PM1 clone. Infection of PM1 by HIV-1BaL was critically dependent on the CD4 receptor, as shown by competition experiments with an anti-CD4 monoclonal antibody (OKT4a) or with soluble CD4. However, the amount of soluble CD4 required for inhibition of HIV-1BaL was approximately 100-fold higher than for HIV-1IIIB, suggesting that the affinity of HIV-1BaL for CD4 is significantly lower. Infection of PM1 with either HIV-1BaL or HIV-1(573) failed to induce downregulation of surface CD4 expression and syncytium formation. Analogous results were obtained with a chimeric virus (HXB2[BaL PvuII-BamHI]) encompassing a large portion of gp120 and gp41 of HIV-1BaL, indicating that the env genes contain critical determinants for CD4 downregulation and syncytium formation. Consistent with the lack of CD4 downregulation, persistent infection of PM1 by HIV-1BaL or HIV-1(573) failed to interfere with HIV-1IIIB superinfection, as revealed by the expression of a type-specific V3 loop epitope (M77) and by the induction of extensive syncytium formation. This lack of interference suggests that a direct viral interaction may occur in vivo between biologically diverse HIV-1 strains.(ABSTRACT TRUNCATED AT 400 WORDS)
The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. (1994)

Stem cell factor (SCF) and its receptor (SCFR), a member of the receptor tyrosine kinase III family that is encoded by the c-kit gene, critically regulate several complex biological programs including hematopoiesis, mast cell development, cutaneous pigmentation, and gametogenesis. We show herein that mouse mast cells die rapidly after the withdrawal of SCF in vivo or in vitro, and provide morphological evidence that such mast cells undergo programmed cell death or apoptosis. We also show that when in vitro-derived mouse mast cells maintained in SCF are removed from SCF-containing medium for only 5 or 6 hours, the cells' genomic DNA exhibits the ladder-like pattern of oligonucleosome-sized fragments typical of apoptosis. These findings demonstrate that SCF can regulate the survival of a cellular lineage which expresses the SCFR by suppressing apoptosis. They also identify a mechanism that can result in striking and rapid reductions in the size of tissue mast cell populations without histological evidence of the concomitant induction of a significant inflammatory response.
A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study (2008)

4508 Background: For nearly ten years gemcitabine (G) was standard first line therapy for patients (pts) with advanced pancreatic cancer (APC). There is no consensus about second line therapy after disease progression while receiving G, but 5-FU-based regimens are considered. Randomized second line studies in APC are very rare. Our phase II study (ASCO 2002) showed activity of the OFF (oxaliplatin/folinic acid (FA)/5-Fluorouracil (FU) [24h] ) regimen in 23 pts. To examine the impact and the side effects of oxaliplatin we initiated a multicenter phase III study to compare OFF and FF in pts with G refractory APC. Methods: Pts with CT/ MRT confirmed PD on G in first line therapy, Karnofsky Performance Status (KPS) >60%, controlled pain, adequate hematological, renal and liver functions were eligible. Pts were stratified according to duration of first line therapy, KPS and tumor stage. We planned to randomized 165 pts to outpatient treatment with FF (5-FU 2g/m² (24h)/ FA 200 mg/m² (30min) on d1, d8, d15 and d22) or OFF (FF+oxaliplatin 85mg/m², d8, d22). In both arms the next cycle started on day 43. Pts were followed with regular staging at least every 3 months or at any signs of disease progression. Results: We recruited 168 pts between 02/2004 and 06/2007. Drop out rate is 4.8%. There is a full data assessment of 160 pts. Conclusions: We are able to present final results (side effects, progression free survival, overall survival) with an one year surveillance after study closure at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology, Pfizer Oncology, sanofi-aventis, GlaxoSmithKline, Amgen, Hoffman-La Roche
A parallel processing tutorial (1990)

An overview of parallel computing is provided, with reference to numerical analysis and, in particular, to computational electromagnetics. The history of parallelism is reviewed, and the general principles are provided. The two main types of parallelism encountered, pipelining and replication are discussed, and an example of each is described. A parallel algorithm for forming a matrix-vector product is presented and analyzed. This is then used as the core of a parallel conjugate gradient algorithm. The theoretically predicted efficiency and the measured efficiency are compared. A glossary and a brief discussion of the available literature on parallel processing are included.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A synthetic impulse noise environment for DSL access networks (2011)

In this paper a multi-statistics model of the impulse noise is presented. An impressive experimental noise data collection acquired from digital access loops provides the synthetic noise environment with the most convenient probability density functions. Internal and external impulse noise sources within communications copper lines are briefly surveyed. A wide-band noise measuring circuit is used to determine the impulse noise properties. Our model gives a full description of the impulse statistics in the time and frequency domains, enables generation of impulses with statistically appropriate both time and spectral characteristics, is based on recent measurements and reflects the current statistics of impulse noise in digital networks, is based on wide-band measurements, agrees with empirical statistics from different access networks in different places.
Arterial and Central Venous Pressure Monitoring (2004)

Pittman, James A. L. MD, BSc, FRCA; Ping, John Sum MD, FRCA; Mark, Jonathan B. MD Author Information
Evolutionary Computation: The Fossil Record (1998)

From the Publisher:
Featuring copious introductory material by distinguished scientist Dr. David B. Fogel, this formidable collection of 30 landmark papers spans the entire history of evolutionary computation---from today's investigations back toits very origins more than 40 years ago. Chapter by chapter, Fogel highlights how early ideas have developed into current thinking and how others have been lost and await rediscovery. The introductions to each chapter reflect Fogel's one-on-one conversations with the authors and their colleagues, conducted over a period of four years. Evolutionary Computation: The Fossil Record provides in-depth historical information and technical detail that is simply unmatched in the field. This volume is complete with an extensive bibliography of related literature.Evolutionary Computation: The Fossil Record will be of particular interest to researchers and students in need of a comprehensive resource on this fascinating area of computer science. Historians will also find thebook thoroughly engaging.This book belongs on the shelf of not only every contributor to evolutionary computation, but to all those who are involved with the more general frontiers of computer science as well as the even broader challenges of complex systems design in all its dimensions.-- George Friedman, Adjunct Professor, Univ. Southern CaliforniaSponsored by:IEEE Neural Networks Council.
Gonococcal opacity protein promotes bacterial entry-associated rearrangements of the epithelial cell actin cytoskeleton (1996)

Neisseria gonorrhoeae enters cultured human mucosal cells following binding of a distinct gonococcal opacity (Opa) outer membrane protein to cell surface proteoglycan receptors. We examined the route of internalization that is activated by Opa-expressing gonococci (strain VP1). Microscopy of infected Chang epithelial cells showed that gonococcal uptake was insensitive to monodansylcadaverine (150 microM), which interferes with clathrin-mediated endocytosis. Similarly, indirect immunofluorescence staining for clathrin in infected cells showed distribution of cellular clathrin unaltered from the distribution in noninfected cells. The microtubule inhibitors colchicine (50 microM) and nocodazole (20 microM) but not the microtubule-stabilizing agent taxol (10 microM) caused a moderate (30 to 50%) reduction in gonococcal entry without affecting bacterial adherence. The most dramatic effects were obtained with the microfilament-disrupting agent cytochalasin D (3 microM), which totally blocked bacterial entry into the cells. Double immunofluorescence staining of gonococci and actin filaments in infected cells demonstrated bacterium-associated accumulations of F-actin as an early signal of bacterial entry. The recruitment of F-actin was transient and disappeared once the bacteria were inside the cells. Cytochalasin D disrupted the actin cytoskeleton architecture but did not prevent the recruitment of F-actin by the bacteria. Adherent, noninvasive gonococcal Opa variants lacked the ability to mobilize F-actin. Recombinant Escherichia coli expressing the gonococcal invasion-promoting Opa of gonococcal strain MS11 (Opa50) adhered to the epithelial cells in an Opa-dependent fashion but was not internalized and did not recruit detectable amounts of F-actin. Coinfection with the E. coli recombinant strain and gonococci resulted in specific entry of the diplococci, despite the presence of large numbers of adherent E. coli cells. Together, our results indicate that Opa-mediated gonococcal entry into Chang cells resembles phagocytosis rather than macropinocytosis reported for Salmonella spp. and sequentially involves gonococcal adherence to the cell surface, Opa-dependent and cytochalasin-insensitive recruitment of F-actin, and cytochalasin D-sensitive bacterial internalization.
Silver Nanodisks:  Synthesis, Characterization, and Self-Assembly (2002)

A new form of silver nanostructured materials, silver nanodisks, are generated by a solution-phase approach. In this method, truncated triangular silver nanoplates are at first fabricated through seed-mediated growth of silver particles in the presence of concentrated cetyltrimethylammonium bromide (CTAB). Subsequent aging of the obtained triangular silver nanoplate solution at 40 °C leads to the formation of silver nanodisks. Transmission electron microscopy and atomic force microscopy studies show that the nanodisks have a thickness of the order of 20−30 nm and a diameter around 60 nm. X-ray and electron diffraction analyses reveal that the nanodisks are single crystals and with their basal plane as the (111) lattice plane. These nanodisks display a strong surface plasmon absorption band at 475 nm. The formation of a self-assembled monolayer of CTAB on the basal plane is suggested to account for both the anisotropic growth from triangular nanoplates to nanodisks and the formation of large-scale necklace-like nanostructures.
Phenylalanine Tolerance in Endogenous Depression (1963)

Penrose (1935), in describing the first British patients with phenylketonuria, noted in their unaffected relatives a high incidence of paranoid illness in later life, and suggested that the heterozygous state might predispose to such breakdown. The 47 phenylketonuric families reported by Munro (1947) showed in unaffected relatives a similar high incidence of psychotic illness, which he (Munro, 1957) categorized as endogenous depression with paranoid features.