gebhart/patrepeval huggingface dataset:
The antiangiogenic protein kinase inhibitors SU5416 and SU6668 inhibit the SCF receptor (c-kit) in a human myeloid leukemia cell line and in acute myeloid leukemia blasts (2001)

SU5416 and SU6668 are potent antiangiogenic small-molecule inhibitors of receptor tyrosine kinases, including those of the vascular endothelial growth factor and platelet-derived growth factor receptor families. The stem cell factor (SCF) receptor, c-kit, is structurally related to these receptors and, although not expressed on mature peripheral blood cells, is expressed in leukemic blasts derived from 60% to 80% of acute myeloid leukemia (AML) patients. The c-kit kinase inhibitory activity of SU5416 and SU6668 was evaluated in MO7E cells, a human myeloid leukemia cell line. Tyrosine autophosphorylation of the receptor, induced by SCF, was inhibited in these cells by SU5416 and SU6668 in a dose-dependent manner (inhibitory concentration of 50% [IC(50)] 0.1-1 microM). Inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, a signaling event downstream of c-kit activation, was also inhibited in a dose-dependent manner. Both compounds also inhibited SCF-induced proliferation of MO7E cells (IC(50) 0.1 microM for SU5416; 0.29 microM for SU6668). Furthermore, both SU5416 and SU6668 induced apoptosis in a dose- and time-dependent manner as measured by the increase in activated caspase-3 and the enhanced cleavage of its substrate poly(ADP-ribose) polymerase. These findings with MO7E cells were extended to leukemic blasts from c-kit(+) patients. In patient blasts, both SU5416 and SU6668 inhibited SCF-induced phosphorylation of c-kit and ERK1/2 and induced apoptosis. These studies indicate that SU5416 and SU6668 inhibit biologic functions of c-kit in addition to exhibiting antiangiogenic properties and suggest that the combination of these activities may provide a novel therapeutic approach for the treatment of AML.
Hatching by example (2002)

We present a new approach to synthetic (computer-aided) drawing with patches of strokes. Grouped strokes convey the local intensity level that is desired in drawing. The key point of our approach is learning by example: the system does not know a priori the distribution of the strokes. Instead, by analyzing a sample (training) patch of strokes, our system is able to synthesize freely an arbitrary sequence of strokes that "looks like" the given sample. Strokes are considered as parametrical curves represented by a vector of random variables following a Markovian distribution. Our method is based on Shannon's N-gram approach and is a direct extension of Efros's texture synthesis models [EL99; EF01]. Nevertheless, one major difference between our method and traditional texture synthesis is the use of such curves as a basic element instead of pixels. We define a statistical metric for comparison between different patches containing various layouts of strokes. We hope that our method performs a first step towards capturing a very difficult notion of style in drawing --- hatching style in our case. We illustrate our method by varied examples, ranging from typical hatching in traditional drawing to highly heterogeneous sets of strokes.
Two-dimensional spectral shearing interferometry for few-cycle pulse characterization (2006)

We present a new method for measuring the spectral phase of ultrashort pulses that utilizes spectral shearing interferometry with zero delay. Unlike conventional spectral phase interferometry for direct electric-field reconstruction, which encodes phase as a sensitively calibrated fringe in the spectral domain, two-dimensional spectral shearing interferometry robustly encodes phase along a second dimension. This greatly reduces demands on the spectrometer and allows for complex phase spectra to be measured over extremely large bandwidths, potentially exceeding 1.5 octaves.
Clinical Effect of Intravenous Calcitriol Administration on Secondary Hyperparathyroidism (2002)

Intravenous calcitriol was found to have a clear dose-dependent effect on PTH reduction in patients with 2HPT, and the appropriate initial dose of this agent was determined to be 1 microg per dialysis session.
Vertical cavity surface-emitting laser with an AlGaAs/AlAs Bragg reflector (1988)

The letter elucidates the room temperature pulsed operation of a vertical cavity surface-emitting (SE) laser with an electrically conductive AlGaAs/AlAs distributed Bragg reflector (DBR). The maximum reflectivity of a DBR grown by MOCVD was 96% at 0.88 μm wavelength. The threshold current of 30 μm diameter devices was 200 mA under room temperature pulsed condition, which is the lowest value for such a broad area structure.
The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport (2004)

Although oxidatively damaged lipoproteins are implicated in vascular injury, there is little information regarding the role of high-density lipoprotein (HDL) oxidation in atherogenesis. One potential pathway involves hypochlorous acid (HOCl) produced by myeloperoxidase (MPO), a heme protein secreted by phagocytes. We previously showed that 3-chlorotyrosine is a specific product of HOCl. Therefore, to explore the role of oxidized HDL in the pathogenesis of vascular disease, we used MS to quantify 3-chlorotyrosine in HDL isolated from plasma and atherosclerotic tissue. HDL from human aortic atherosclerotic intima had an 8-fold higher level of 3-chlorotyrosine than plasma HDL. Tandem MS analysis identified MPO as a component of lesion HDL, suggesting that the two interact in the artery wall. Moreover, immunohistochemical studies found that specific epitopes derived from HOCl colocalized with apolipoprotein A-I, the major protein of HDL. These observations strongly support the hypothesis that MPO promotes HDL oxidation in the human artery wall. Levels of 3-chlorotyrosine were elevated in HDL isolated from the blood of humans with established coronary artery disease, suggesting that circulating levels of oxidized HDL represent a unique marker for clinically significant atherosclerosis. HDL or lipid-free apolipoprotein A-I exposed to HOCl was less able to remove cholesterol from cultured cells by a pathway requiring the cell membrane transporter ATP-binding cassette transporter A1. The detection of 3-chlorotyrosine in HDL isolated from vascular lesions raises the possibility that MPO, by virtue of its ability to form HOCl, may promote atherogenesis by counteracting the established antiatherogenic effects of HDL and the ATP-binding cassette transporter A1 pathway.
Central sensitisation in visceral pain disorders: Figure 1 (2006)

The concepts of visceral hyperalgesia and visceral hypersensitivity have been examined in a variety of functional gastrointestinal disorders (FGIDs). Although the pathophysiological mechanisms of pain and hypersensitivity in these disorders are still not well understood, exciting new developments in research have been made in the study of the brain-gut interactions involved in the FGIDs.
Identification of Soft Matter Binding Peptide Ligands Using Phage Display (2015)

Phage display is a powerful tool for the selection of highly affine, short peptide ligands. While originally primarily used for the identification of ligands to proteins, the scope of this technique has significantly expanded over the past two decades. Phage display nowadays is also increasingly applied to identify ligands that selectively bind with high affinity to a broad range of other substrates including natural and biological polymers as well as a variety of low-molecular-weight organic molecules. Such peptides are of interest for various reasons. The ability to selectively and with high affinity bind to the substrate of interest allows the conjugation or immobilization of, e.g., nanoparticles or biomolecules, or generally, facilitates interactions at materials interfaces. On the other hand, presentation of peptide ligands that selectively bind to low-molecular-weight organic materials is of interest for the development of sensor surfaces. The aim of this article is to highlight the opportunities provided by phage display for the identification of peptide ligands that bind to synthetic or natural polymer substrates or to small organic molecules. The article will first provide an overview of the different peptide ligands that have been identified by phage display that bind to these "soft matter" targets. The second part of the article will discuss the different characterization techniques that allow the determination of the affinity of the identified ligands to the respective substrates.
The tumor microenvironment as a determinant of cancer cell survival: a possible mechanism for de novo drug resistance (2000)

The influence of the microenvironment in the pathogenesis and progression of human cancer has traditionally been considered in the context of solid tumors. More recently, evidence has been accumulating to support the role of the bone marrow microenvironment in hematologic malignancies as well, particularly in multiple myeloma. This review focuses on myeloma as a model to demonstrate that the bone marrow microenvironment provides a sanctuary against programmed cell death and promotes tumor cell survival and progression. Additionally, the protective effects of the bone marrow milieu may confer a protection from cytotoxic drugs, allowing the emergence of drug-resistant tumors. These advances may assist in the design of novel therapeutic approaches to enhance the efficacy of standard chemotherapeutic drugs.
Poly(methyl hydrogen siloxane) (PMHS) XPS Reference Core Level and Energy Loss Spectra (2005)

XPS measurements of poly(methyl hydrogen siloxane) recorded with a SSX-100 spectrometer in standardized experimental conditions are presented: survey scan, high resolution core level spectra as well as the energy loss regions of carbon and oxygen peaks are analyzed. This is part of a contract work aiming to record spectra in the very same conditions of some 40 different polymers.
Cardiac and Glycemic Benefits of Troglitazone Treatment in NIDDM (1997)

Troglitazone is a thiazolidinedione under development for the treatment of NIDDM and potentially other insulin-resistant disease states. Treatment with troglitazone is associated with an improvement in hyperglycemia, hyperinsulinemia, and insulin-mediated glucose disposal. No significant side effects have been observed in humans. Because of reported cardiac changes in animals treated with drugs of this class, this multicenter 48-week study was conducted to evaluate whether NIDDM patients treated with troglitazone develop any cardiac mass increase or functional impairment. A total of 154 NIDDM patients were randomized to receive troglitazone 800 mg q.d. or glyburide titrated to achieve glycemic control (< or =20 mg b.i.d. or q.d.). Two-dimensional echocardiography and pulsed Doppler were used to measure left ventricular mass index (LVMI), cardiac index (CI), and stroke volume index (SVI). All echocardiograms were performed at each center (baseline, 12, 24, 36, and 48 weeks), recorded on videotape, and forwarded to a blinded central echocardiographic interpreter for analysis. The results showed that LVMI of patients treated with troglitazone was not statistically or clinically different from baseline after 24 or 48 weeks. Statistically significant increases in SVI and CI and a statistically significant decrease in diastolic pressure and estimated peripheral resistance were observed in troglitazone-treated patients. These results were not sex-specific. Glycemic benefits of troglitazone treatment were observed as evidenced by long-term improvement of HbA1c and C-peptide levels. Furthermore, triglycerides were significantly lower, and HDL was significantly higher at weeks 24 and 48. In conclusion, NIDDM patients treated with troglitazone do not show any cardiac mass increase or cardiac function impairment. Conversely, patients on troglitazone benefited from enhanced cardiac output and stroke volume, possibly as a result of decreased peripheral resistance. Treatment with troglitazone appears to have a favorable impact on known cardiovascular risk factors and could potentially lower cardiovascular morbidity in NIDDM patients.
β-Catenin Mediates Mechanically Regulated, Transforming Growth Factor-β1–Induced Myofibroblast Differentiation of Aortic Valve Interstitial Cells (2010)

Myofibroblast differentiation of VICs involves matrix stiffness-dependent crosstalk between TGF-β1 and Wnt signaling pathways and may explain in part why the stiffer fibrosa is more susceptible to disease.
Fractionation of Serum Components Using Nanoporous Substrates (2006)

Numerous previously uncharacterized molecules resident within the low molecular weight circulatory proteome may provide a picture of the ongoing pathophysiology of an organism. Recently, proteomic signatures composed of low molecular weight molecules have been identified using mass spectrometry combined with bioinformatic algorithms. Attempts to sequence and identify the molecules that underpin the fingerprints are currently underway. The finding that many of these low molecular weight molecules may exist bound to circulating carrier proteins affords a new opportunity for fractionation and separation techniques prior to mass spectrometry-based analysis. In this study we demonstrate a method whereby nanoporous substrates may be used for the facile and reproducible fractionation and selective binding of the serum-based biomarker material, including subcellular proteins found within the serum. Aminopropyl-coated nanoporous silicon, when exposed to serum, can deplete serum of proteins and yield a serum with a distinct, altered MS profile. Additionally, aminopropyl-coated, nanoporous controlled-pore glass beads are able to bind a subset of serum proteins and release them with stringent elution. The eluted proteins have distinct MS profiles, gel electrophoresis profiles, and differential peptide sequence identities, which vary based on the size of the nanopores. These material surfaces could be employed in strategies for the harvesting and preservation of labile and carrier-protein-bound molecules in the blood.
wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye (1995)

In the developing Drosophila compound eye, a wave of pattern formation and cell-type determination sweeps across the presumptive eye epithelium. This 'morphogenetic furrow' coordinates the epithelial cells' division cycle, shape and gene expression to produce evenly spaced neural cell clusters that will eventually form the adult ommatidia. As these clusters develop, they rotate inwards to face the eye's equator and establish tissue polarity. We have found that wingless is strongly expressed in the dorsal margin of the presumptive eye field, ahead of the morphogenetic furrow. We have shown that inactivation of Wingless results in the induction of an ectopic furrow that proceeds ventrally from the dorsal margin. This ectopic furrow is normal in most respects, however the clusters formed by it fail to rotate, and we propose a two-vector model to account for normal rotation and tissue polarity in the retina. A second consequence of this inactivation of Wingless is that the dorsal head is largely deleted. We have also found that patched loss-of-function mosaic clones induce circular ectopic morphogenetic furrows (consistent with the observations of other workers with the hedgehog, and PKA genes). We use such patched induced furrows to test the two-vector model for cluster rotation and tissue polarity.
Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates (2010)

Made for each other: Combinatorial alanine substitution of active site residues in a thermostable cytochrome P450BM3 variant was used to generate an enzyme that is active with large substrates. Selective hydroxylation of methoxymethylated monosaccharides, alkaloids, and steroids was thus made possible (see Scheme). This approach could be useful for improving the activity of enzymes that show only limited activity with larger substrates.
Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses (1998)

PD-1, an Ig superfamily member, contains an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic tail. It is expressed in a minor fraction of CD4-CD8- normal thymocytes and induced in peripheral lymphocytes following activation. To assess the possible roles of PD-1 in the immune responses, PD-1-deficient (PD-1-/-) mice were generated by a gene-targeting strategy. PD-1-4- mice developed and grew normally. Although the thymus was apparently normal, PD-1-/- mice showed moderate but consistent splenomegaly, which reflected the increased cellularity of both lymphoid and myeloid cells. The proliferative response of B cells by anti-IgM antibodies, but not of T cells by an anti-CD3 (145-2C11) mAb in vitro, was augmented in PD-1-/- mice as compared with control littermates. PD-1-/- mice showed increased serum levels of IgG2b, IgA and most strikingly IgG3, while those of IgM and IgG1 were comparable with control mice. Furthermore, PD-1-/- mice exhibited significantly augmented IgG3 anti-DNP antibody response to a type 2 T-independent antigen, DNP-Ficoll, with comparable IgM and IgG1 antibody responses with littermate controls. In the peritoneal cavity, the B-1 cell population in PD-1-/- mice exhibited significantly reduced expression of CD5, a negative regulator of B-1 cell activation, despite a marginal increase in the number of B-1 cells. Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching.
Purification and some kinetic properties of rat liver glucosamine synthetase (1971)

1. Glucosamine synthetase (l-glutamine-d-fructose 6-phosphate aminotransferase, EC 2.6.1.16) was purified about 300-fold from rat liver by two techniques. One procedure utilized the protective action of fructose 6-phosphate and gave a relatively stable preparation, the other yielded an unstable enzyme (half-life of about 20h), free of contaminant activities, on which kinetic experiments were performed. Although the properties of the two preparations showed slight differences, the unstabilized form could be converted into the stabilized form. 2. During preparation the enzyme retained its sensitivity to the feedback inhibitor, UDP-N-acetylglucosamine. 3. The reversibility of the enzyme-catalysed reaction could not be demonstrated. There was no apparent requirement for a cofactor. 4. The pH optimum was at 7.5, at which pH the reaction obeyed a Ping Pong Bi Bi rate equation. At pH values outside the range 6.9-7.6 and at temperatures below 29 degrees C the velocity was described by an ordered Bi Bi rate equation. 5. The molecular weight of the enzyme, determined by two procedures, was 360000-400000. 6. The aminotransferase was unable to utilize ammonia as a substrate.
Fiber optic gyros: the vision realized (2006)

Over thirty five years have elapsed since the fiber optic gyro was proposed by Vali and Shorthill. In those decades, fiber gyros have matured. They are competing head to head with existing technologies such as mechanical gyros and RLGs in tactical, navigation and strategic applications and are winning. Northrop Grumman has produced the majority of fiber optic gyros and fiber optic gyro based inertial products in the world. This paper will cover the various Northrop fiber gyro products, the platforms they are used on, as well as production and top level system data.
A High-Voltage Bipolar Transconductance Amplifier for Electrotactile Stimulation (2008)

This paper describes a high-performance transconductance amplifier specifically designed for electrotactile (electrocutaneous) stimulation. It enables voltages up to +/-600 V to be produced at the output that will allow the psychophysiological performance associated with stimulation of the fingertip using various stimulation waveforms to be studied more thoroughly. The design has a transconductance of up to 20 mA/V, an 8.8-Momega output resistance, and can provide output currents up to +/-20 mA. A complete schematic diagram is presented along with a discussion of theory of operation and safety issues as well as performance and derating plots from the implemented design.
Mutations in the VHL Gene Are the Major Identified Cause of Inherited Erythrocytosis. (2005)

Abstract The molecular basis of inherited erythrocytosis in most patients remains to be defined. Although all such patients have an absolute increase in red cell mass, their erythropoietin (EPO) levels differ widely, so they constitute a heterogeneous group of disorders known collectively as idiopathic erythrocytosis (IE). A proportion of individuals with IE progress to polycythemia vera (PV), a clonal disorder arising from a multipotent progenitor. Recently a gain-of-function mutation in Janus kinase 2 (JAK2), V617F, has been described in myeloproliferative disorders (MPD) and a stream of publications has confirmed its presence in the majority of patients with PV. Screening IE patients for this mutation will provide a useful additional means for delineating inherited and clonal disorders of erythrocytosis. Over the last decade we have maintained a registry of British and Irish erythrocytosis patients, consisting of clinical information and DNA samples obtained following full ethical approval. Screening the EPO receptor (EPO-R) in 120 patients identified one patient with a G6002A mutation, which leads to truncation of the receptor by 70 amino acids, increased sensitivity to EPO, and erythrocytosis. Screening the same patients for mutations in the von Hippel Lindau (VHL) gene has revealed individuals from 8 families of Asian origin who are homozygous for the Chuvash (R200W) mutation causing erythrocytosis. In addition, one Caucasian individual of English descent is compound heterozygous for R200W and the recently described G144R VHL mutation. A further individual, D1 (Percy et al, 2003Blood102:1097), of the same ethnicity is heterozygous for the Chuvash mutation and has been found to express the wild type allele. Both his mother and son, who are heterozygous for the Chuvash mutation, do not have IE, suggesting that the patient harbors a second unidentified genetic defect. Several such individuals have already been described (reviewed by Randi et al, 2005 Haematologica 90:689). In order to estimate the proportion of IE patients likely to progress to PV, 65 individuals from the registry with EPO levels in the low to normal range were screened by amplification refractory mutation system (ARMS) PCR for the MPD-associated V617F JAK2 mutation. Two individuals were positive, one of whom subsequently proceeded rapidly to PV, while the other has remained stable without any disease progression. In addition 9 families with VHL mutations were also screened and all were found to be negative for the JAK2 mutation, suggesting that the occurrence of these mutations tends to be mutually exclusive. Also the V617F JAK2 mutation does not constitute the second genetic defect in patient D1 who is heterozygous for the Chuvash VHL mutation. Although VHL mutations are the most frequent cause of inherited erythrocytosis in our registry they are present in only ~10% of patients, while the gain-of-function of JAK2 mutation is rare, leaving ~90% of the IE cases unexplained. Further study of this group may reveal additional regulatory mechanisms involved in red cell homeostasis.