gebhart/patrepeval huggingface dataset:
Engagement of P-selectin Glycoprotein Ligand-1 Enhances Tyrosine Phosphorylation and Activates Mitogen-activated Protein Kinases in Human Neutrophils (1997)

During inflammation, P-selectin on activated platelets and endothelial cells initiates adhesion of leukocytes through interactions with P-selectin glycoprotein ligand-1 (PSGL-1). We investigated whether ligation of PSGL-1 also transmits signals into leukocytes. Neutrophils incubated with anti-PSGL-1 monoclonal antibodies, but not with Fab fragments of these antibodies, rapidly increased tyrosine phosphorylation of proteins with relative molecular masses of 105-120, 70-84, and 42-44 kDa. PSGL-1-dependent adhesion of neutrophils to P-selectin increased tyrosine phosphorylation of similarly sized proteins. Cytochalasin B did not prevent the tyrosine phosphorylation induced by ligation of PSGL-1, suggesting that an intact cytoskeleton is not required for signaling. Engagement of PSGL-1 activated the GTPase Ras through a mechanism that did not require tyrosine phosphorylation of PSGL-1 or association of the Shc.Grb2.Sos1 complex with PSGL-1. Engagement of PSGL-1 activated the 42-44-kDa extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinases through a pathway that required activation of the MAP kinase kinase. Ligation of PSGL-1 also stimulated secretion of interleukin-8. The tyrosine kinase inhibitor, genistein, blocked tyrosine phosphorylation and secretion of interleukin-8, whereas the MAP kinase kinase inhibitor PD98059 partially inhibited secretion of interleukin-8. Tyrosine phosphorylation stimulated through PSGL-1 on selectin-tethered leukocytes may propagate a signaling cascade that is integrated with signals generated by other mediators.
Administration of an anti-IgE antibody inhibits CD23 expression and IgE production in vivo. (1994)

High IgE responder BDF1 mice were immunized intraperitoneally (i.p.) with dinitrophenol4 (DNP4)-ovalbumin (OVA) in alum concomitant with intravenous (i.v.) administration of an anti-IgE monoclonal antibody (mAb). IgE levels were undetectable in mice treated with the anti-IgE antibody, whereas mice treated with isotype-matched irrelevant mAb had IgE levels comparable to that of untreated, immunized mice. Subsequent antigen challenges with DNP4-OVA, either at weekly or monthly intervals, failed to evoke an IgE response for greater than 2 months in mice treated with anti-IgE during the primary sensitization, even though the terminal half-life of the anti-IgE antibody was 7 days. This inhibition was specific for DNP4-OVA since the DNP4-OVA-suppressed mice were able to respond to keyhole limpet haemocyanin (KLH). To investigate the effects of antibody treatment at the cellular level, passive transfer experiments were performed. The primary DNP-specific IgE response of adoptive transfer recipient mice was the same whether the donor cells were from mice treated with IgG or anti-IgE. Transfer of enriched T- or B-cell populations indicated that T-cell help was not compromised by administration of the anti-IgE mAb. However, splenocytes from the anti-IgE-treated mice failed to synthesize IgE in vitro, and flow cytometric analysis of B cells from anti-IgE-treated mice showed a dose-dependent decrease in CD23+ cells following antibody treatment, which correlated with decreased serum IgE levels. Taken together, the results of these studies suggest that anti-IgE treatment suppresses IgE responses via effects on B cells rather than T cells, possibly through effects on CD23-dependent pathways.
Zonisamide for Weight Loss in Obese Adults (2003)

In this short-term, preliminary trial, zonisamide and hypocaloric diet resulted in more weight loss than placebo and hypocaloric diet in the treatment of obesity.
Inflammation and adipose tissue macrophages in lipodystrophic mice (2009)

Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-kappaB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance.
Searching objects in large-scale indoor environments: A decision-theoretic approach (2012)

Many of today's mobile robots are supposed to perform everyday manipulation tasks autonomously. However, in large-scale environments, a task-related object might be out of the robot's reach. Hence, the robot first has to search for the object in its environment before it can perform the task. In this paper, we present a decision-theoretic approach for searching objects in large-scale environments using probabilistic environment models and utilities associated with object locations. We demonstrate the feasibility of our approach by integrating it into a robot system and by conducting experiments where the robot is supposed to search different objects with various strategies in the context of fetch-and-delivery tasks within a multi-level building.
Do Incretin-Based Therapies Cause Acute Pancreatitis? (2010)

In 2007 a question was raised about the causal relationship between the first of the glucagon-like peptide 1 receptor agonists, exenatide, and pancreatitis, as postmarketing reports of pancreatitis in patients treated with this agent had been received by the Food and Drug Administration (FDA). There had been six reports of hemorrhagic pancreatitis, with two of the cases resulting in death. An update of the package insert for Byetta was mandated. Sitagliptin entered the market about a year and a half later, and now there are similar reports of acute pancreatitis. As the number of patients treated with these agents increases, is it uncovering a risk not appreciated in the premarket phase or just what should be expected from the population treated with these agents? To date, 88 cases of acute pancreatitis have been reported to the FDA in patients taking sitagliptin (Januvia/Janumet). Of these, two cases have been hemorrhagic or necrotizing pancreatitis. A revision of the package insert for sitagliptin has been made recently. An examination of available data should help shed light on whether the relation is likely causal or merely incidental.
Multidimensional adaptive sampling and reconstruction for ray tracing (2008)

We present a new adaptive sampling strategy for ray tracing. Our technique is specifically designed to handle multidimensional sample domains, and it is well suited for efficiently generating images with effects such as soft shadows, motion blur, and depth of field. These effects are problematic for existing image based adaptive sampling techniques as they operate on pixels, which are possibly noisy results of a Monte Carlo ray tracing process. Our sampling technique operates on samples in the multidimensional space given by the rendering equation and as a consequence the value of each sample is noise-free. Our algorithm consists of two passes. In the first pass we adaptively generate samples in the multidimensional space, focusing on regions where the local contrast between samples is high. In the second pass we reconstruct the image by integrating the multidimensional function along all but the image dimensions. We perform a high quality anisotropic reconstruction by determining the extent of each sample in the multidimensional space using a structure tensor. We demonstrate our method on scenes with a 3 to 5 dimensional space, including soft shadows, motion blur, and depth of field. The results show that our method uses fewer samples than Mittchell's adaptive sampling technique while producing images with less noise.
Flexibilization of the work schedule, one of the most wanted facilities after the end of the pandemic (2022)

In recent years we have witnessed a series of important changes in labor law, determined both by the need of companies to keep their employees motivated and productive, and by the trends imposed by the new generations that give more importance to personal and professional life. who prefer flexible hours, to the detriment of the rigid standards imposed by the relevant legislation. Many employees want a more flexible work schedule once the Covid-19 pandemic is over and they will have to return to work. Some opt for moderate options, while others want to make significant changes, such as adopting a hybrid work regime. This requires that employees be able to choose their work schedule and also where they want to work. If most of the countries in which the 4-day-a-week work schedule was tested considered a proportional reduction in the number of hours worked in a week with the maintenance of the salary unchanged, it should be noted that in Romania and Belgium, the concept of short working week only considers a merging of the 40-hour working week into 4 working days and the granting of 3 days off. Another way to make work more flexible regulated by the Labor Code is the individualized work schedule. However, an important aspect, which deserves to be pointed out and which concerns both situations described above, is the one related to the fact that, once the state of alert is over, the regulation of telework will be done exclusively based on Law no. 81/
The tyrosine kinase inhibitor ZD1839 ("Iressa") inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. (2001)

The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors and provides a new target for anticancer drug development. ZD1839 ("Iressa"), a quinazoline tyrosine kinase inhibitor selective for the EGFR, has shown good activity in preclinical studies and in the early phase of clinical trials. However, because it remains unclear which tumor types are the best targets for treatment with this agent, the molecular characteristics that correlate with tumor sensitivity to ZD1839 have been studied. In a panel of human breast cancer and other epithelial tumor cell lines, HER2-overexpressing tumors were particularly sensitive to ZD1839. Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR, HER2, and HER3, accompanied by the loss of association of HER3 with phosphatidylinositol 3-kinase, and down-regulation of Akt activity. These studies suggest that HER2-overexpressing tumors are particularly susceptible to the inhibition of HER family tyrosine kinase signaling and suggest novel strategies to treat these particularly aggressive tumors.
Automatic SIMD vectorization for Haskell (2013)

Expressing algorithms using immutable arrays greatly simplifies the challenges of automatic SIMD vectorization, since several important classes of dependency violations cannot occur. The Haskell programming language provides libraries for programming with immutable arrays, and compiler support for optimizing them to eliminate the overhead of intermediate temporary arrays. We describe an implementation of automatic SIMD vectorization in a Haskell compiler which gives substantial vector speedups for a range of programs written in a natural programming style. We compare performance with that of programs compiled by the Glasgow Haskell Compiler.
Lysophosphatidic acid stimulates the proliferation and motility of malignant pleural mesothelioma cells through lysophosphatidic acid receptors, LPA1 and LPA2 (2008)

Lysophosphatidic acid (LPA) is one of the simplest natural phospholipids. This phospholipid is recognized as an extracellular potent lipid mediator with diverse effects on various cells. Although LPA is shown to stimulate proliferation and motility via LPA receptors, LPA(1) and LPA(2), in several cancer cell lines, the role of LPA and LPA receptors for malignant pleural mesothelioma (MPM) has been unknown. MPM is an aggressive malignancy with a poor prognosis and the incidence is increasing and is expected to increase further for another 10-20 years worldwide. Therefore, the development of novel effective therapies is needed urgently. In this study, we investigated the effect of LPA on the proliferation and motility of MPM cells. We found that all 12 cell lines and four clinical samples of MPM expressed LPA(1), and some of them expressed LPA(2), LPA(3), LPA(4) and LPA(5). LPA stimulated the proliferation and motility of MPM cells in a dose-dependent manner. Moreover, LPA-induced proliferation was inhibited by Ki16425, an inhibitor of LPA(1), and small interfering RNA against LPA(1), but not LPA(2). Interestingly, LPA-induced motility was inhibited by small interfering RNA against LPA(2), but not LPA(1), unlike a number of previous reports. These results indicate that LPA is a critical factor on proliferation though LPA(1), and on motility though LPA(2) in MPM cells. Therefore, LPA and LPA receptors, LPA(2) as well as LPA(1), represent potential therapeutic targets for patients with MPM.
Effect of the CH2NH and CH2NAc peptide bond isosteres on the antagonistic and histamine releasing activities of a luteinizing hormone-releasing hormone analog (1988)

The effect of the CH2NH and CH2NAc peptide bond isosteres on the antagonistic and histamine releasing activities of the LH-RH antagonist [N-Ac-D-Nal1,D-Phe2,3,D-Arg6,Phe7,D-Ala10] LH-RH was investigated. The moieties were introduced by facile, racemization-free solid-phase synthesis in an attempt to reduce the histamine releasing activity inherent to the most potent analogues while retaining high antiovulatory activity. The psi [CH2NH] isostere was incorporated at each CONH site with the exception of 8-9, which involves Pro, by reductive alkylation with a protected amino acid aldehyde in the presence of NaBH3CN during conventional solid-phase peptide synthesis. The psi [CH2NH] group was extremely resistant to derivatization and could only be partially acetylated to give psi [CH2NAc]. The analogues were cleaved from the resin with simultaneous deprotection by anhydrous hydrogen fluoride and purified to homogeneity in two stages: gel permeation followed by preparative reversed-phase liquid chromatography. The analogues were assayed in standard rat antiovulatory and in vitro histamine release assays. The isosteres caused a loss of the antiovulatory activity of the antagonist at the 50-microgram dose when incorporated at the positions 1-2, 2-3, 3-4, and 7-8. Incorporation at the other positions resulted in a less marked reduction in activity relative to the unmodified parent analogue. No significant effect was noted on the potent histamine releasing activity of the analogues.
Materials Integration by Dip‐Pen Nanolithography (2010)

Abstract Dip‐pen nanolithography (DPN) is a versatile tool for nanotechnology that enables the resolution of electron‐beam lithography, integration capabilities typical of inkjet printing, and a high throughput comparable to microcontact printing. By using the tip of an atomic force microscope as an ultra‐sharp pen, DPN represents a constructive method of scanning probe lithography that can be carried out in a massively parallel fashion. This chapter introduces the fundamental concepts in DPN technology, with a focus on aspects that enable materials integration. Theoretical models of ink transport are discussed, and a variety of experimental methods presented. The concept of a driving force is explained, along with various methods for controlling that driving force, both by ink–substrate combinations, humidity and the application of external fields. Various approaches to tip coating are explained and suitable characterization methods presented. Finally, examples of unique applications of materials integration by DPN will be described that cannot be achieved by any other method, including templates, combinatorial chemistry and biological arrays.
Combined cannabinoid therapy via an oromucosal spray (2006)

Extensive basic science research has identified the potential therapeutic benefits of active compounds extracted from the Cannabis sativa L. plant (the cannabinoids). It is recognized that a significant proportion of patients suffering with the debilitating symptoms of pain and spasticity in multiple sclerosis or other conditions smoke cannabis despite the legal implications and stigma associated with this controlled substance. GW Pharmaceuticals have developed Sativex (GW- 1,000-02), a combined cannabinoid medicine that delivers and maintains therapeutic levels of two principal cannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), via an oromucosal pump spray, that aims to minimize psychotropic side effects. Sativex has proved to be well tolerated and successfully self-administered and self-titrated in both healthy volunteers and patient cohorts. Clinical assessment of this combined cannabinoid medicine has demonstrated efficacy in patients with intractable pain (chronic neuropathic pain, pain due to brachial plexus nerve injury, allodynic peripheral neuropathic pain and advanced cancer pain), rheumatoid arthritis and multiple sclerosis (bladder problems, spasticity and central pain), with no significant intoxication-like symptoms, tolerance or withdrawal syndrome.
Prevention of diabetic nephropathy in mice by a diet low in glycoxidation products (2002)

Intake of high-level, food-derived AGEs is a major contributor to DN in T1D and T2D mice. Avoidance of dietary AGEs provides sustained protection against DN in mice; providing the rationale for similar studies in human diabetic patients.
The human immunodeficiency virus type 2 vpr gene is essential for productive infection of human macrophages. (1990)

The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site-specific mutagenesis of a biologically active HIV-2 proviral clone (HIV-2sbl/isy), which is infectious in both human T cells and macrophages. Viral progeny carrying mutations of nef, vpr, or of both nef and vpr genes replicated more efficiently than the parental virus in primary human peripheral blood cells and in the human Hut 78 T-cell line. In contrast, the HIV-2 nef- mutant infected human macrophages as efficiently as the parental virus, whereas viruses lacking the vpr gene either alone or in conjunction with the lack of the nef gene did not replicate in macrophages. Thus, some lack of nef in HIV-2 enhances viral replication in T cells and does not interfere with viral replication in primary macrophages, whereas vpr is essential for replication of HIV-2 in human macrophages. Because the parental HIV-2sbl/isy cloned virus also infects rhesus macaques, the use in animal studies of these HIV-2 mutants with differences in cell tropism and rates of replication will be highly useful in understanding the mechanism of viral infectivity and possibly pathogenicity in vivo.
Interactions between Conjugated Polymers and Single-Walled Carbon Nanotubes (2002)

The chemical interactions between single walled carbon nanotubes (SWNTs) and two structurally similar polymers, poly{(m-phenylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]}, or PmPV, and poly{(2,6-pyridinylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]}, or PPyPV, are investigated. The fundamental difference between these two polymers is that PPyPV is a base and is readily protonated via the addition of HCl. Both polymers promote chloroform solubilization of SWNTs. We find that the SWNT/PPyPV interaction lowers the pKa of PPyPV. Optoelectronic devices, fabricated from single polymer-wrapped SWNT structures, reveal a photogating effect on charge transport which can rectify or amplify current flow through the tubes. For PmPV wrapped tubes, the wavelength dependence of this effect correlates to the absorption spectrum of PmPV. For PPyPV, the wavelength dependence correlates with the absorption spectrum of protonated PPyPV, indicating that SWNTs assist in charge stabilization.
Electrochemical Behavior of Nonflammable Organo-Fluorine Compounds for Lithium Ion Batteries (2009)

The electrochemical behavior of organo-fluorine compounds with antioxidation ability has been investigated. Oxidation currents of fluorine-compound-containing ethylene carbonate (EC)/diethyl carbonate (DEC) solutions were much smaller than those of EC/DEC and EC/DEC/propylene carbonate (PC) at potentials higher than 6 V vs . Electrochemical reduction of fluorine compounds started at ca. 2 V vs , higher than those for EC, DEC, and PC. However the first coulombic efficiencies for natural graphite electrodes in fluorine-compound-containing EC/DEC mixtures were nearly the same as those in EC/DEC without an increase in irreversible capacities. Furthermore the first coulombic efficiencies in fluorine-compound-containing EC/DEC/PC mixtures were much larger than those in EC/DEC/PC itself. The results show that the fluorine compounds used in the present study can be used as nonflammable solvents for lithium ion batteries.
Beagle puppy model of intraventricular hemorrhage (1985)

Intraventricular hemorrhage (IVH) represents a major problem for preterm neonates and is thought to occur secondary to alterations in cerebral blood flow (CBF) to damaged germinal matrix tissues. Many investigators believe that both local CBF and changes in capillary morphology and permeability may be partially controlled by prostaglandins. To evaluate this hypothesis, the authors have studied the effects of superoxide dismutase (SOD), a known free-radical scavenger, on newborn beagle pups that were randomly assigned by computer to four groups consisting of either SOD- or saline-pretreated animals that underwent either insult by hemorrhagic hypotension/volume reexpansion or no insult. Prostaglandin levels were determined prior to and 60 minutes following the administration of the solutions, and carbon-14 iodoantipyrine autoradiography was performed for determination of CBF. It was demonstrated that, although SOD significantly decreased the incidence of IVH in this model (p less than 0.05), it caused no alterations in baseline CBF or prostaglandin levels. In addition, SOD did not prevent either the systemic blood pressure changes or the alterations in CBF found in response to a hemorrhagic hypotensive insult. The authors propose that neonatal IVH results from a combination of factors, one of which is prostaglandin-mediated alterations in CBF to a damaged capillary matrix.