gebhart/patrepeval huggingface dataset:
Molecularly Targeted Therapy for Gastrointestinal Cancer (2005)

Receptor and non-receptor tyrosine kinases (TKs) have emerged as clinically useful drug target molecules for treating gastrointestinal cancer. Imatinib mesilate (STI-571, Gleevec(TM)), an inhibitior of bcr-abl TK, which was primarily designed to treat chronic myeloid leukemia is also an inhibitor of c-kit receptor TK, and is currently the drug of choice for the therapy of metastatic gastrointestinal stromal tumors (GISTs), which frequently express constitutively activated forms of the c-kit-receptor. The epidermal growth factor receptor (EGFR), which is involved in cell proliferation, metastasis and angiogenesis, is another important target. The two main classes of EGFR inhibitors are the TK inhibitors and monoclonal antibodies. Gefitinib (ZD1839, Iressa(TM)) has been on trial for esophageal and colorectal cancer (CRC) and erlotinib (OSI-774, Tarceva(TM)) on trial for esophageal, colorectal, hepatocellular, and biliary carcinoma. In addition, erlotinib has been evaluated in a Phase III study for the treatment of pancreatic cancer. Cetuximab (IMC-C225, Erbitux(TM)), a monoclonal EGFR antibody, has been FDA approved for the therapy of irinotecan resistant colorectal cancer and has been tested for pancreatic cancer. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are critical regulators of tumor angiogenesis. Bevacizumab (Avastin(TM)), a monoclonal antibody against VEGF, was efficient in two randomized clinical trials investigating the treatment of metastatic colorectal cancer. It is also currently investigated for the therapy of pancreatic cancer in combination with gemcitabine. Other promising new drugs currently under preclinical and clinical evaluation, are VEGFR2 inhibitor PTK787/ZK 222584, thalidomide, farnesyl transferase inhibitor R115777 (tipifarnib, Zarnestra(TM)), matrix metalloproteinase inhibitors, proteasome inhibitor bortezomib (Velcade(TM)), mammalian target of rapamycin (mTOR) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, platelet derived growth factor receptor (PDGF-R) inhibitors, protein kinase C (PKC) inhibitors, mitogen-activated protein kinase kinase (MEK) 1/2 inhibitors, Rous sarcoma virus transforming oncogene (SRC) kinase inhibitors, histondeacetylase (HDAC) inhibitors, small hypoxia-inducible factor (HIF) inhibitors, aurora kinase inhibitors, hedgehog inhibitors, and TGF-beta signalling inhibitors.
Passive protection of mice, goats, and monkeys against Japanese encephalitis with monoclonal antibodies (1989)

Six monoclonal antibodies (McAbs) against Japanese encephalitis virus (JEV) were tested for passive protection in JEV-infected mice, goats, and rhesus monkeys. mG9 and nG2 had no protective effect; mG3 and 2D2 had some protective effect, but not sufficient to be of therapeutic significance; and 2H4 and 2F2 had excellent protective efficacy in mice even 120 hr after infection when most of the mice in the virus control group were sick. The mixture of 2H4, 2F2, mC3 (M-McAb), and their F(ab')2 fragments showed excellent protection in mice, goats, and monkeys and was safe. The protective effects of McAbs correlated with their neutralization titers, but cytotoxicity-mediated activities also played a role in protection.
A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse (2011)

Spinal muscular atrophy (SMA) is an autosomal-recessive disorder characterized by α-motor neuron loss in the spinal cord anterior horn. SMA results from deletion or mutation of the Survival Motor Neuron 1 gene (SMN1) and retention of SMN2. A single nucleotide difference between SMN1 and SMN2 results in exclusion of exon 7 from the majority of SMN2 transcripts, leading to decreased SMN protein levels and development of SMA. A series of splice enhancers and silencers regulate incorporation of SMN2 exon 7; these splice motifs can be blocked with antisense oligomers (ASOs) to alter SMN2 transcript splicing. We have evaluated a morpholino (MO) oligomer against ISS-N1 [HSMN2Ex7D(-10,-29)], and delivered this MO to postnatal day 0 (P0) SMA pups (Smn-/-, SMN2+/+, SMNΔ7+/+) by intracerebroventricular (ICV) injection. Survival was increased markedly from 15 days to >100 days. Delayed CNS MO injection has moderate efficacy, and delayed peripheral injection has mild survival advantage, suggesting that early CNS ASO administration is essential for SMA therapy consideration. ICV treatment increased full-length SMN2 transcript as well as SMN protein in neural tissue, but only minimally in peripheral tissue. Interval analysis shows a decrease in alternative splice modification over time. We suggest that CNS increases of SMN will have a major impact on SMA, and an early increase of the SMN level results in correction of motor phenotypes. Finally, the early introduction by intrathecal delivery of MO oligomers is a potential treatment for SMA patients.
<title>Image quality metrics for halftone images</title> (1992)

In this paper, different factors that affect the quality of a halftone image are examined. We investigated the quality of constant-gray-level halftones, and also of more complex halftone images with various content and degree of detail. For the constant-gray-level halftones, it was examined how their visual appearance changes with variations in their power spectrum characteristics, and for the more complex halftone images we investigated how different quantitative quality metrics can describe the quality of these images. Since the ultimate judges of image quality are human viewers, the success of the quantitative metrics as quality measures for halftones was assessed by comparing their results with the results of a psychovisual test.
The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function. (1989)

A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps SH2 domain stimulated the enzymatic activity of the adjacent kinase domain 10-fold and functioned as a powerful positive effector of catalytic and transforming activities within the v-fps oncoprotein (P130gag-fps). Partial proteolysis of P130gag-fps and supporting genetic data indicated that the v-fps SH2 domain exerts its effect on catalytic activity through an intramolecular interaction with the kinase domain. Amino acid alterations in the SH2 domain that impaired kinase function interfered with association of the SH2 domain with the kinase domain. Deletion of a conserved octapeptide motif converted the v-fps SH2 domain from an activator to an inhibitor of tyrosine kinase activity. This latent inhibitory activity of v-fps SH2 has functional implications for phospholipase C-gamma and p21ras GTPase-activating protein, both of which have two distinct SH2 domains suggestive of complex regulation. In addition to regulating the specific activity of the kinase domain, the SH2 domain of P130gag-fps was also found to be required for the tyrosine phosphorylation of specific cellular proteins, notably polypeptides of 124 and 62 kilodaltons. The SH2 domain therefore appears to play a dual role in regulation of kinase activity and recognition of cellular substrates.
Examination of the platelet membrane glycoprotein IIb-IIIa complex and its interaction with fibrinogen and other ligands by electron microscopy. (1992)

The platelet integrin, glycoprotein IIb-IIIa (GPIIb-IIIa), is a calcium-dependent heterodimer that binds fibrinogen, von Willebrand factor, and fibronectin after platelet activation. We examined GPIIb-IIIa alone and bound to these ligands by electron microscopy after rotary shadowing with platinum/tungsten. We found, as observed previously, that in the presence of detergent and 2 mM Ca2+, GPIIb-IIIa consists of an 8 x 12-nm globular head with two 18-nm flexible tails extending from one side. We also found that in the presence of EDTA, GPIIb-IIIa dissociates into two similar comma-shaped subunits, each containing a portion of the globular head and a single tail. Using monoclonal antibodies to GPIIb, GPIIIa, and the GPIIb-IIIa heterodimer, we found that the tails contained the carboxyl termini of each subunit, while the nodular head was composed of amino-terminal segments of both subunits. Electron microscopy of GPIIb-IIIa bound to fibrinogen revealed a highly specific interaction of the nodular head of GPIIb-IIIa with the distal end of the trinodular fibrinogen molecule and with the tails of GPIIb-IIIa extended laterally at an angle of approximately 98 degrees with respect to the long axis of fibrinogen. When a GPIIb-IIIa was bound to each end of a single fibrinogen, the tails were oriented to opposite sides of fibrinogen, enabling fibrinogen to bridge two adjacent platelets. Electron microscopy of GPIIb-IIIa bound to fibronectin revealed GPIIb/IIIa-binding sites approximately two-thirds of the distance from the amino terminus of each end of the fibronectin molecule, while GPIIb-IIIa was found to bind to von Willebrand factor protomers along a rod-like region near the central nodule of the molecule.
Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse. (1994)

Proglucagon mRNA transcripts are transcribed in the pancreas, bowel, and brain, after which posttranslational processing results in the liberation of a different profile of biologically active peptides in each tissue. The receptors for two of these peptides, glucagon and glucagon-like peptide-1 (GLP-1), have recently been identified, but only limited information is available concerning the tissue- and age-specific distribution of these receptors in vivo. We have investigated the expression of these receptors in the mouse using a combination of Northern blot analysis and reverse transcription-polymerase chain reaction. DNA sequence analysis of a partial mouse glucagon receptor cDNA demonstrated a high degree of sequence conservation across rodent species. Glucagon receptor mRNA transcripts were detectable by Northern blotting in poly(A)+ RNA from liver and kidney. Reverse transcription-polymerase chain reaction also detected glucagon receptor mRNA transcripts in both fetal and adult pancreas and lung, jejunum, and ileum, but not in the large intestine. In contrast, mRNA transcripts for the GLP-1 receptor were detected in both small and large intestine as well as in pancreas, liver, lung, and kidney. Both glucagon and GLP-1 receptor mRNA transcripts were identified in different regions of the fetal and adult mouse brain, but the relative levels of GLP-1 receptor mRNA transcripts were much greater in the central nervous system. Furthermore, regulation of the GLP-1 receptor (but not the glucagon receptor) gene in the brain resembled the pattern of region-specific gene expression recently defined for the mouse proglucagon gene. Taken together, these studies define novel sites for both glucagon and GLP-1 receptor gene expression in the mouse and suggest that different regulatory mechanisms have evolved for tissue-specific and developmental control of receptor gene expression.
TiO2 Photocatalysis: A Historical Overview and Future Prospects (2005)

Photocatalysis has recently become a common word and various products using photocatalytic functions have been commercialized. Among many candidates for photocatalysts, TiO 2 is almost the only material suitable for industrial use at present and also probably in the future. This is because TiO 2 has the most efficient photoactivity, the highest stability and the lowest cost. More significantly, it has been used as a white pigment from ancient times, and thus, its safety to humans and the environment is guaranteed by history. There are two types of photochemical reaction proceeding on a TiO 2 surface when irradiated with ultraviolet light. One includes the photo-induced redox reactions of adsorbed substances, and the other is the photo-induced hydrophilic conversion of TiO 2 itself. The former type has been known since the early part of the 20th century, but the latter was found only at the end of the century. The combination of these two functions has opened up various novel applications of TiO 2 , particularly in the field of building materials. Here, we review the progress of the scientific research on TiO 2 photocatalysis as well as its industrial applications, and describe future prospects of this field mainly based on the present authors' work.
Differential Diagnosis of Glomerular Disease: A Systematic and Inclusive Approach (2013)

This work is intended to facilitate accurate diagnosis in the individual patient presenting with evidence of glomerular disease.
Potassium Channels and Membrane Potential in the Modulation of Intracellular Calcium in Vascular Endothelial Cells (2004)

The endothelium plays a vital role in the control of vascular functions, including modulation of tone; permeability and barrier properties; platelet adhesion and aggregation; and secretion of paracrine factors. Critical signaling events in many of these functions involve an increase in intracellular free Ca(2+) concentration ([Ca(2+)](i)). This rise in [Ca(2+)](i) occurs via an interplay between several mechanisms, including release from intracellular stores, entry from the extracellular space through store depletion and second messenger-mediated processes, and the establishment of a favorable electrochemical gradient. The focus of this review centers on the role of potassium channels and membrane potential in the creation of a favorable electrochemical gradient for Ca(2+) entry. In addition, evidence is examined for the existence of various classes of potassium channels and the possible influence of regional variation in expression and experimental conditions.
Limiting dilution assay for human B cells based on their activation by mutant EL4 thymoma cells: total and anti‐malaria responder B cell frequencies (1987)

The analysis of human B cell responses at the clonal level (limiting dilution assay) is still technically difficult. In the present study we report on a culture system that leads to activation, proliferation and differentiation into antibody-secreting cells (ASC) of about 90% of B cells from peripheral blood or spleen. In this system, B cells are cultured in the presence of a mutant subclone of the mouse thymoma EL4 for B cell activation and human T cell plus macrophage supernatant as source of proliferation and differentiation factors. ASC precursors generating clonal responses of IgM only, IgM plus IgG, or IgG only occurred at a ratio of about 6:3:1. The mean clone size was 380 cytoplasmic Ig+ cells; the mean amount of Ig secreted per clone was 20 ng. Furthermore, it has been found using this system that a considerable proportion of peripheral blood B cells from individuals with a history of malaria infection could generate clones of anti-malaria (Plasmodium falciparum) ASC (range of 0.1 to 1%, n = 6). In a control group of blood donors the corresponding frequencies were 10 times lower (range of 0.01 to 0.1%, n = 9). These results show that the EL4 culture system can be applied to the investigation of the human B cell specificity repertoire and of priming effects such as result from infectious disease.
Inefficacy of 17 alpha-hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy. (1980)

There are indications that prophylactic administration of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) could be beneficial in the treatment of women at risk for preterm delivery. Since twin pregnancy is commonly associated with prematurity, 77 women with twin pregnancy were treated during the last trimester until the 37th gestational week with weekly injections of either 17 alpha-OHP-C or a placebo, following double-blind principles. The gestational length and birth weight and the outcome of the neonates were similar in both groups. The administration of 17 alpha-OHP-C thus seems ineffective in the prevention of prematurity risks associated with twin pregnancy.
Current status on Alzheimer disease molecular genetics: from past, to present, to future (2010)

Linkage studies, candidate gene and whole-genome association studies have resulted in a tremendous amount of putative risk genes for Alzheimer's disease (AD). Yet, besides the three causal genes-amyloid precursor protein and presenilin 1 and 2 genes-and one risk gene apolipoprotein E (APOE), no single functional risk variant was identified. Discussing the possible involvement of rare alleles and other types of genetic variants, this review summarizes the current knowledge on the genetic spectrum of AD and integrates different approaches and recent discoveries by genome-wide association studies.
Bayesian Statistics: An Introduction (1998)

Bayesian Statistics is the school of thought that combines prior beliefs with the likelihood of a hypothesis to arrive at posterior beliefs. The first edition of Peter Lees book appeared in 1989, but the subject has moved ever onwards, with increasing emphasis on Monte Carlo based techniques.This new fourth edition looks at recent techniques such as variational methods, Bayesian importance sampling, approximate Bayesian computation and Reversible Jump Markov Chain Monte Carlo (RJMCMC), providing a concise account of the way in which the Bayesian approach to statistics develops as well as how it contrasts with the conventional approach. The theory is built up step by step, and important notions such as sufficiency are brought out of a discussion of the salient features of specific examples.This edition:Includes expanded coverage of Gibbs sampling, including more numerical examples and treatments of OpenBUGS, R2WinBUGS and R2OpenBUGS.Presents significant new material on recent techniques such as Bayesian importance sampling, variational Bayes, Approximate Bayesian Computation (ABC) and Reversible Jump Markov Chain Monte Carlo (RJMCMC).Provides extensive examples throughout the book to complement the theory presented.Accompanied by a supporting website featuring new material and solutions.More and more students are realizing that they need to learn Bayesian statistics to meet their academic and professional goals. This book is best suited for use as a main text in courses on Bayesian statistics for third and fourth year undergraduates and postgraduate students.
microRNA-506 regulates proliferation, migration and invasion in hepatocellular carcinoma by targeting F-spondin 1 (SPON1). (2015)

Our previous study indicates microRNA-506 (miR-506) is downregulated in hepatocellular carcinoma (HCC). In the current study, we investigate the effects of miR-506 on proliferation, migration and invasion in HCC. We report that enforced expression of miR-506 inhibits proliferation, migration and invasion in vitro, and suppresses tumor growth in vivo. Conversely, suppression of miR-506 exhibits promoting effects on proliferation, migration and invasion in vitro, and on tumor growth in vivo. In addition, miR-506 binds to the 3'UTR of F-spondin 1(SPON1), and enforced expression of miR-506 decreases accumulation of SPON1. Moreover, enforced expression of SPON1 and suppression of SPON1 alleviates effects of miR-506 mimics and inhibitors on proliferation, migration and invasion in vitro, respectively. In conclusion, microRNA-506 regulates proliferation, migration and invasion in HCC by targeting SPON1.
Light regulates expression of brain-derived neurotrophic factor mRNA in rat visual cortex. (1992)

Specific sensory input has profound transient and long-lasting effects on the function of corresponding sensory cortical areas both during development and in adulthood. To study whether neurotrophic factors might play a role in such processes, we investigated the effects of light on the nerve growth factor and brain-derived neurotrophic factor (BDNF) mRNA levels in rat visual cortex. Keeping adult rats in the dark or preventing normal activity of retinal ganglion cells by intraocular injection of tetrodotoxin significantly decreased the levels of BDNF mRNA in the visual cortex but not in other cortical areas. Exposure to light after a period in darkness rapidly restored the mRNA to control levels. These alterations in visual input had no effect on nerve growth factor mRNA. The mRNA of trkB, the putative signal-transducing receptor unit for BDNF, was also decreased in darkness, although less than BDNF mRNA. BDNF mRNA levels increased in the visual cortex of newborn rats after eye-opening. This increase is retarded, although not completely abolished, by rearing the pups in darkness. Thus, the levels of BDNF mRNA are rapidly regulated by sensory input during development and in adulthood. BDNF may therefore play an important role in formation and in activity-dependent modulation of specific connections in the visual cortex.
Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults (2003)

Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.
Simple analytical expressions for the fringing field and fringing-field-induced transfer time in charge-coupled devices (1991)

The author presents simple analytical solutions for the potential and the fringing field, especially for charge-coupled devices (CCDs). A description of the influence of the insulation layer in terms of an equivalent substrate thickness is used to find expressions for the optimal charge transport depth and charge transfer time for small charge packets in CCDs. The thickness of the insulation layer is accounted for by a scaling rule that is a nonlinear function of the thickness and dielectric constant of the insulation layer and the lateral dimensions of the device. Compared with computer simulations this technique gives good results for surface potentials that are found in CCDs. The results are used to calculate the optimal transfer depth and minimal transfer time in bulk and surface CCDs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mitochondrial p32 is upregulated in Myc expressing brain cancers and mediates glutamine addiction (2014)

Metabolic reprogramming is a key feature of tumorigenesis that is controlled by oncogenes. Enhanced utilization of glucose and glutamine are the best-established hallmarks of tumor metabolism. The oncogene c-Myc is one of the major players responsible for this metabolic alteration. However, the molecular mechanisms involved in Myc-induced metabolic reprogramming are not well defined. Here we identify p32, a mitochondrial protein known to play a role in the expression of mitochondrial respiratory chain complexes, as a critical player in Myc-induced glutamine addiction. We show that p32 is a direct transcriptional target of Myc and that high level of Myc in malignant brain cancers correlates with high expression of p32. Attenuation of p32 expression reduced growth rate of glioma cells expressing Myc and impaired tumor formation in vivo. Loss of p32 in glutamine addicted glioma cells induced resistance to glutamine deprivation and imparted sensitivity to glucose withdrawal. Finally, we provide evidence that p32 expression contributes to Myc-induced glutamine addiction of cancer cells. Our findings suggest that Myc promotes the expression of p32, which is required to maintain sufficient respiratory capacity to sustain glutamine metabolism in Myc transformed cells.