gebhart/patrepeval huggingface dataset:
Comparative analyses of gene copy number and mRNA expression in glioblastoma multiforme tumors and xenografts (2009)

Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.
The effects of ischaemic preconditioning, diazoxide and 5‐hydroxydecanoate on rat heart mitochondrial volume and respiration (2002)

Studies with different ATP-sensitive potassium (K(ATP)) channel openers and blockers have implicated opening of mitochondrial K(ATP) (mitoK(ATP)) channels in ischaemic preconditioning (IPC). It would be predicted that this should increase mitochondrial matrix volume and hence respiratory chain activity. Here we confirm this directly using mitochondria rapidly isolated from Langendorff-perfused hearts. Pre-ischaemic matrix volumes for control and IPC hearts (expressed in microl per mg protein +/- S.E.M., n = 6), determined with (3)H(2)O and [(14)C]sucrose, were 0.67 +/- 0.02 and 0.83 +/- 0.04 (P < 0.01), respectively, increasing to 1.01 +/- 0.05 and 1.18 +/- 0.02 following 30 min ischaemia (P < 0.01) and to 1.21 +/- 0.13 and 1.26 +/- 0.25 after 30 min reperfusion. Rates of ADP-stimulated (State 3) and uncoupled 2-oxoglutarate and succinate oxidation increased in parallel with matrix volume until maximum rates were reached at volumes of 1.1 microl ml(-1) or greater. The mitoK(ATP) channel opener, diazoxide (50 microM), caused a similar increase in matrix volume, but with inhibition rather than activation of succinate and 2-oxoglutarate oxidation. Direct addition of diazoxide (50 microM) to isolated mitochondria also inhibited State 3 succinate and 2-oxoglutarate oxidation by 30 %, but not that of palmitoyl carnitine. Unexpectedly, treatment of hearts with the mitoK(ATP) channel blocker 5-hydroxydecanoate (5HD) at 100 or 300 microM, also increased mitochondrial volume and inhibited respiration. In isolated mitochondria, 5HD was rapidly converted to 5HD-CoA by mitochondrial fatty acyl CoA synthetase and acted as a weak substrate or inhibitor of respiration depending on the conditions employed. These data highlight the dangers of using 5HD and diazoxide as specific modulators of mitoK(ATP) channels in the heart.
Strong large deviations for composite hypothesis testing (2014)

A simple hypothesis P is tested against a composite hypothesis ℚ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</sup> , j ∈ {1,2, ...,k}, each ℚ <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">j</sup> being a product of n probability distributions. We consider the set of achievable false-positive error probability vectors for a generalized Neyman-Pearson test under a constraint on the probability of correct detection under P. Exact asymptotics (as n → ∞) are derived for this set, in particular the set is determined within an O(1) term.
Sécheresse et fléau acridien en Chine : le cas du Criquet migrateur, Locusta migratoria manilensis (Meyen) (1996)

En Chine, la secheresse, l’inondation et le fleau acridien du au Criquet migrateur, Locusta migratoria manilensis (Meyen), sont les trois calamites naturelles majeures pour l’agriculture, d’autant qu’elles ne sont pas independantes les unes des autres. Une synthese de la relation entre la secheresse et l’invasion de Locusta est proposee, ainsi que la strategie preventive et la lutte contre cet acridien qui en sont deduites. Le probleme acridien est contr⊚le dans son ensemble depuis la fin des annees 60 en Chine, mais le Criquet migrateur reste une espece dangereuse qu’il convient de surveiller.
Rabbit interleukin-1 receptor antagonist. Cloning, expression, functional characterization, and regulation during intestinal inflammation. (1994)

Genomic and cDNA clones for rabbit interleukin-1 receptor antagonist (IL-1ra) were isolate based on homology with the human, mouse, and rat IL-1ra gene. A partial genomic clone, obtained by screening a rabbit genomic library, contained coding sequences for the carboxyl-terminal 108 amino acids of rabbit IL-1ra. Two classes of cDNA for rabbit IL-1ra were obtained using RNA from inflamed rabbit colon tissue. One class of cDNA coded for a secreted form of IL-1ra, whereas the other coded for a putative intracellular form of rabbit IL-1ra. The latter form is similar to that isolated from human epithelial cells. A partially synthetic rabbit IL-1ra gene was constructed and expressed in Escherichia coli. The recombinant rabbit IL-1ra was purified to homogeneity by ion exchange chromatography. Its affinity was similar to that of human IL-1ra for the human and mouse type I IL-1 receptor. From the cDNA clone and the purified recombinant protein, specific probes were developed for measuring levels of rabbit IL-1ra mRNA and protein in normal and inflamed rabbit tissues. Unlike IL-1 alpha and IL-1 beta, IL-1RA mRNA and protein were present at detectable levels in normal rabbit colon. During the development of an experimental formalin-immune complex colitis, rabbit IL-1 alpha showed a dramatic increase in tissue levels, consistent with previous results; IL-1ra also increased 3-4-fold. Treatment of colitis rabbits with corticosteroids significantly suppressed neutrophil infiltration, corticosteroid treatment suppressed IL-1ra but not IL-1 alpha mRNA steady-state levels. Our observations demonstrate that IL-1 and IL-1ra synthesis is differentially regulated in healthy and inflamed intestinal tissue.
Full-Length Plasmodium falciparum Circumsporozoite Protein Administered with Long-Chain Poly(I·C) or the Toll-Like Receptor 4 Agonist Glucopyranosyl Lipid Adjuvant-Stable Emulsion Elicits Potent Antibody and CD4+T Cell Immunity and Protection in Mice (2012)

The Plasmodium falciparum circumsporozoite (CS) protein (CSP) is a major vaccine target for preventing malaria infection. Thus, developing strong and durable antibody and T cell responses against CSP with novel immunogens and potent adjuvants may improve upon the success of current approaches. Here, we compare four distinct full-length P. falciparum CS proteins expressed in Escherichia coli or Pichia pastoris for their ability to induce immunity and protection in mice when administered with long-chain poly(I · C) [poly(I · C)LC] as an adjuvant. CS proteins expressed in E. coli induced high-titer antibody responses against the NANP repeat region and potent CSP-specific CD4(+) T cell responses. Moreover, E. coli-derived CS proteins in combination with poly(I · C)LC induced potent multifunctional (interleukin 2-positive [IL-2(+)], tumor necrosis factor alpha-positive [TNF-α(+)], gamma interferon-positive [IFN-γ(+)]) CD4(+) effector T cell responses in blood, in spleen, and particularly in liver. Using transgenic Plasmodium berghei expressing the repeat region of P. falciparum CSP [Pb-CS(Pf)], we showed that there was a 1- to 4-log decrease in malaria rRNA in the liver following a high-dose challenge and ~50% sterilizing protection with a low-dose challenge compared to control levels. Protection was directly correlated with high-level antibody titers but not CD4(+) T cell responses. Finally, protective immunity was also induced using the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) as the adjuvant, which also correlated with high antibody titers yet CD4(+) T cell immunity that was significantly less potent than that with poly(I · C)LC. Overall, these data suggest that full-length CS proteins and poly(I · C)LC or GLA-SE offer a simple vaccine formulation to be used alone or in combination with other vaccines for preventing malaria infection.
Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue (2000)

The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer.
Molecular Cloning of a Novel α2,3-Sialyltransferase (ST3Gal VI) That Sialylates Type II Lactosamine Structures on Glycoproteins and Glycolipids (1999)

A novel member of the human CMP-NeuAc:beta-galactoside alpha2, 3-sialyltransferase (ST) subfamily, designated ST3Gal VI, was identified based on BLAST analysis of expressed sequence tags, and a cDNA clone was isolated from a human melanoma line library. The sequence of ST3Gal VI encoded a type II membrane protein with 2 amino acids of cytoplasmic domain, 32 amino acids of transmembrane region, and a large catalytic domain with 297 amino acids; and showed homology to previously cloned ST3Gal III, ST3Gal IV, and ST3Gal V at 34, 38, and 33%, respectively. Extracts from L cells transfected with ST3Gal VI cDNA in a expression vector and a fusion protein with protein A showed an enzyme activity of alpha2, 3-sialyltransferase toward Galbeta1,4GlcNAc structure on glycoproteins and glycolipids. In contrast to ST3Gal III and ST3Gal IV, this enzyme exhibited restricted substrate specificity, i.e. it utilized Galbeta1,4GlcNAc on glycoproteins, and neolactotetraosylceramide and neolactohexaosylceramide, but not lactotetraosylceramide, lactosylceramide, or asialo-GM1. Consequently, these data indicated that this enzyme is involved in the synthesis of sialyl-paragloboside, a precursor of sialyl-Lewis X determinant.
Human Gene Therapy (1993)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Towards wearable sensing-based assessment of fluid intake (2010)

Fluid intake is an important information for many health and assisted living applications. At the same time it is inherently difficult to monitor. Existing reliable solutions require augmented drinking containers, which severely limits the applicability of such systems. In this paper we investigate two key components of an unobtrusive, wearable solution that is independent of a particular drinking container or environment. We first describe a system for spotting individual instances of drinking (lifting a container to the mouth and taking a single sip) in a continuous stream of data from a wrist-worn acceleration sensor. We show that drinking motion can be detected across different drinking containers (glass, cup, large beer mug, bottle) on a large dataset (560 drinking motion instances from six users, embedded in 5.84 hours of complex natural activities). An average performance of 84% recall at 94% precision was achieved for the drinking motion spotting. Based on the events derived from drinking event spotting, we show how additional information can be obtained. Specifically, we demonstrate the recognition of container types and fluid level from upper body postures during drinking events. Nine containers and three container fluid levels were evaluated to recognize container type and fluid amounts with three users. Recognition rate for container type was 75%, and for fluid level 72%.
Bcl-2 Is a Prognostic Marker in Breast Cancer Independently of the Nottingham Prognostic Index (2006)

Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.
C‐C chemokine receptor 2 (CCR2) deficiency improves bleomycin‐induced pulmonary fibrosis by attenuation of both macrophage infiltration and production of macrophage‐derived matrix metalloproteinases (2004)

Macrophage infiltration is implicated in various types of pulmonary fibrosis. One important pathogenetic process associated with pulmonary fibrosis is injury to basement membranes by matrix metalloproteinases (MMPs) that are produced mainly by macrophages. In this study, C-C chemokine receptor 2-deficient (CCR2-/-) mice were used to explore the relationship between macrophage infiltration and MMP activity in the pathogenesis of pulmonary fibrosis, using the bleomycin-induced model of this disease process. CCR2 is the main (if not only) receptor for monocyte chemoattractant protein-1/C-C chemokine ligand 2 (MCP-1/CCL2), which is a critical mediator of macrophage trafficking, and CCR2 -/- mice demonstrate defective macrophage migration. Pulmonary fibrosis was induced in CCR2-/- and wild-type (CCR2+/+) mice by intratracheal instillation of bleomycin. No significant differences in the total protein concentration in bronchoalveolar lavage (BAL) fluid, or in the degree of histological lung inflammation, were observed in the two groups until day 7. Between days 3 and 21, however, BAL fluid from CCR2-/- mice contained fewer macrophages than BAL fluid from CCR2+/+ mice. Gelatin zymography of BAL fluid and in situ zymography revealed reduced gelatinolytic activity in CCR2-/- mice. Immunocytochemical staining showed weaker expression of MMP-2 and MMP-9 in macrophages in BAL fluid from CCR2-/- mice at day 3. Gelatin zymography of protein extracted from alveolar macrophages showed reduced gelatinolytic activity of MMP-2 and MMP-9 in CCR2-/- mice. At days 14 and 21, lung remodelling and the hydroxyproline content of lung tissues were significantly reduced in CCR2-/- mice. These results suggest that the CCL2/CCR2 functional pathway is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis and that CCR2 deficiency may improve the outcome of this disease by regulating macrophage infiltration and macrophage-derived MMP-2 and MMP-9 production.
Colloidal gold--low density lipoprotein conjugates as membrane receptor probes. (1981)

We have developed a method for conjugating low density lipoproteins (LDL) with colloidal gold. Conjugation, complete after 1 min, occurs by electrostatic adsorption of the LDL to the negatively charged gold particle. Each conjugate consists of approximately eight biologically active LDL molecules clustered around a central 19-nm gold granule. Acidic (pH 4), alkaline (pH 9), or high ionic (600 milliosmolar NaCl) environments do not dissociate the conjugate. Colloidal gold is an electron-dense, nondegradable marker that is easily identified within the cell and serves as a valuable probe for studying receptor binding and endocytosis. By using a modified method of ruthenium red staining, the LDL molecules of the conjugate can be directly visualized when they are bound to the cell surface receptor. Receptor binding (4 degrees C) of the conjugate by cultured human fibroblasts reveals that the gold granule is positioned 18-21 nm from the coated pit region of the membrane. This distance, similar to the diameter of LDL, suggests concomitant internalization of the receptor during vesicular endocytosis and early lysosomal incorporation (10 min at 37 degrees C). Continued internalization (30-60 min at 37 degrees C) results in the formation of free pools of gold within the lysosome.
Conductivity study by complex impedance spectroscopy of Na3Nb4As3O19 (2015)

Crystals of Na3Nb4As3O19 were synthesized by a solid-state reaction. It crystallizes in the orthorhombic system, space group C2221 with a = 13.014(2) Å, b = 24.170(3) Å and c = 5.0880(9) Å. The structure can be described as a three-dimensional anionic framework containing two kinds of tunnels parallel to [001] direction where Na+ cations are located. The ionic conductivity was measured, on pellets of polycrystalline powders, between 573 and 893 K in the frequency range 0.01–13000 kHz through the complex impedance method. A correlation between electrical and structural properties was also discussed. Keywords: Three-dimensional framework, IR spectroscopy, CI spectroscopy, Ionic conductivity
Cattle Production Systems to Meet Future Consumer Demands (1984)

In recent years beef cattle production has not been routinely profitable because of continuing increases in production costs and decreases in per capita consumption of beef. Consumers appear to be demanding that beef be competitively priced with other animal protein sources and that its composition, or fat content, be modified to result in optimum nutritional value. Consumers will continue to demand highly palatable beef products. Reestablishing consumer confidence and demand for beef will be important for profitability in the industry. Because it is more costly to produce fat than muscle, production costs could be reduced significantly by marketing cattle with less fat. The beef cattle industry is challenged to synchronize the diversity in genetic resources with production resources and environments. Production is optimized when breeding female genotypes are crossed with sire genotypes. Breeding females should be crosses of Bos indicus and Bos taurus breeds where the environment is suitable. The value of cattle as harvestors of roughage will continue to be important, and the potential of the ruminant digestive system must be fully utilized. Feed grains will remain the primary energy source for finishing cattle, but shorter finishing periods will be utilized for conventional breeds of cattle. Accelerated, or highly intensive feeding systems will be utilized for faster growing, more muscular genotypes. The industry must decrease the emphasis on “feeding quality into beef” and accept the large volume of research that shows a weak relationship between marbling and palatability of beef from young, grain finished cattle. The compositional end point at which production efficiency, processing efficiency, optimum beef nutrition and sensory traits are optimized is in the early stage of fattening. Cattle production systems must assume the role of efficiently producing muscle with some fat included. Meat processing technology must assume a greater role in assuring consumer acceptance of beef in the future.
An Eastern Cooperative Oncology Group phase I-II pilot study of polyriboinosinic-polyribocytidylic acid poly-L-lysine complex in patients with metastatic malignant melanoma. (1985)

Sixteen patients with metastatic malignant melanoma were treated with poly(I,C)-LC 5 mg/m2 twice weekly by intravenous injection. No antitumor responses occurred. Fever (frequently greater than 40 degrees C) and fatigue were dose limiting toxicities. One patient developed a fever of 42.2 degrees C when poly(I,C)-LC was given on 2 consecutive days. Interferon was consistently detected in the serum 8 h after a single injection of poly(I,C)-LC (median titer 199 U/ml). No enhancement of interferon induction was detected on the second day when poly(I,C)-LC was given on 2 consecutive days.
Erythrocyte Receptors for ( Plasmodium Knowlesi ) Malaria: Duffy Blood Group Determinants (1975)

Duffy blood group negative human erythrocytes (FyFy) are resistant to infection by Plasmodium knowlesi, a simian malaria that infects Duffy positive human erythrocytes. The P. knowlesi resistance factor, Duffy negative erythrocytes, occurs in high frequency in West Africa, where the people are resistant to vivax malaria. This suggests that Duffy blood group determinants (Fya or Fyb) may be erythrocyte receptors for P. vivax.
Label-free detection of DNA hybridization using carbon nanotube network field-effect transistors (2006)

We report carbon nanotube network field-effect transistors (NTNFETs) that function as selective detectors of DNA immobilization and hybridization. NTNFETs with immobilized synthetic oligonucleotides have been shown to specifically recognize target DNA sequences, including H63D single-nucleotide polymorphism (SNP) discrimination in the HFE gene, responsible for hereditary hemochromatosis. The electronic responses of NTNFETs upon single-stranded DNA immobilization and subsequent DNA hybridization events were confirmed by using fluorescence-labeled oligonucleotides and then were further explored for label-free DNA detection at picomolar to micromolar concentrations. We have also observed a strong effect of DNA counterions on the electronic response, thus suggesting a charge-based mechanism of DNA detection using NTNFET devices. Implementation of label-free electronic detection assays using NTNFETs constitutes an important step toward low-cost, low-complexity, highly sensitive and accurate molecular diagnostics.
Estrogen plus Progestin and the Risk of Coronary Heart Disease (2003)

Estrogen plus progestin does not confer cardiac protection and may increase the risk of CHD among generally healthy postmenopausal women, especially during the first year after the initiation of hormone use. This treatment should not be prescribed for the prevention of cardiovascular disease.