gebhart/patrepeval huggingface dataset:
A comprehensive catalogue of somatic mutations from a human cancer genome (2009)

All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic.
12 nm tunable WDM source using an integrated laserarray (2000)

A 12 nm tunable source with up to 15 mW fibre coupled power has been fabricated by integrating four DFB lasers and a booster amplifier to provide a single output. High-yield and low-cost techniques are used, such as quarter-wave-shifted phase-masks for wavelength definition and an integration technique with only two regrowths.
Hepatocyte Nuclear Factor 4α, a Key Factor for Homeostasis, Cell Architecture, and Barrier Function of the Adult Intestinal Epithelium (2009)

Hepatocyte nuclear factor 4alpha (HNF-4alpha) is a transcription factor which is highly expressed in the intestinal epithelium from duodenum to colon and from crypt to villus. The homeostasis of this constantly renewing epithelium relies on an integrated control of proliferation, differentiation, and apoptosis, as well as on the functional architecture of the epithelial cells. In order to determine the consequences of HNF-4alpha loss in the adult intestinal epithelium, we used a tamoxifen-inducible Cre-loxP system to inactivate the Hnf-4a gene. In the intestines of adult mice, loss of HNF-4alpha led to an increased proliferation in crypts and to an increased expression of several genes controlled by the Wnt/beta-catenin system. This control of the Wnt/beta-catenin signaling pathway by HNF-4alpha was confirmed in vitro. Cell lineage was affected, as indicated by an increased number of goblet cells and an impairment of enterocyte and enteroendocrine cell maturation. In the absence of HNF-4alpha, cell-cell junctions were destabilized and paracellular intestinal permeability increased. Our results showed that HNF-4alpha modulates Wnt/beta-catenin signaling and controls intestinal epithelium homeostasis, cell function, and cell architecture. This study indicates that HNF-4alpha regulates the intestinal balance between proliferation and differentiation, and we hypothesize that it might act as a tumor suppressor.
Transcutaneous electrical nerve stimulation of the hypoglossal nerve as adjuvant treatment of obstructive sleep apnea (2013)

Hypoglossal nerve stimulation has been demonstrated to relieve upper airway obstruction acutely; implantable devices for hypoglossal nerve stimulation have shown potential functional improvement. The aim of this study was to determine the effect of transcutaneous electrical nerve stimulation (TENS) of the hypoglossal nerve as a noninvasive adjuvant therapy for obstructive sleep apnea (OSA). A total of 25 patients with OSA were examined. Snoring, the apnea–hypopnea index, daytime sleepiness, Mallampati grading, and Friedman tongue position were examined at baseline and after TENS application. Nerve conduction studies including amplitude and distal motor latency were performed before and after TENS application. TENS was applied for stimulation of the hypoglossal nerve for three sets per week for 1 month. Hypoglossal nerve stimulation using TENS showed a significant improvement in daily snoring, severe apnea–hypopnea index, moderately excessive daytime sleepiness, and Friedman tongue position grade III in the studied patients after the physiotherapy program compared with before (P<0.01). The frequency of patients with delayed distal latency of the hypoglossal nerve decreased after TENS therapy (50% of patients had delayed latency in the left and 37.5% of patients had the same in the right hypoglossal nerve). The mean left distal latency of the patients decreased significantly after TENS therapy when compared with before therapy (2.23± 0.52 vs. 3.17± 0.98 ms, respectively, P= 0.0026). The mean right distal latency of the patients also decreased significantly after TENS therapy when compared with before therapy (2.31 ±0.29 vs. 3.32± 1.12 ms, respectively, P= 0.023). The findings demonstrate the feasibility and therapeutic potential of hypoglossal nerve stimulation using TENS in OSA.
Developmental and tissue-specific expression directed by the alpha 2 type I collagen promoter in transgenic mice. (1986)

Eight transgenic mice were generated in which the promoter of the mouse alpha 2(I) collagen gene (nucleotides -2000 to +54), linked to the bacterial gene for chloramphenicol acetyltransferase (CAT), is stably integrated in the germ line. These strains contain from 1 to 20 copies of the alpha 2(I) collagen-CAT chimeric gene per haploid genome. In seven of the eight strains, the CAT gene is expressed, although the levels of CAT enzyme activity vary considerably from one strain to the other. In six of these strains, the expression of the CAT gene follows the expected tissue distribution pattern of expression of the alpha 2(I) collagen gene. In these six strains, the level of CAT activity is much higher in extracts of tail, a tissue that is very rich in tendons, than in any other tissue that was tested. This distribution parallels the much higher levels of alpha 2(I) collagen RNA that are found in the tail as compared to other tissues. Expression of the chimeric gene is detected in the embryo after 8.5 days of gestation, at approximately the same time that the endogenous type I genes become active. We conclude that the alpha 2(I) collagen promoter sequences present in the recombinant plasmid used for our experiments contain sufficient information to ensure stage- and tissue-specific activity of this promoter.
Human poly(ADP‐ribose) polymerase gene (1990)

The promoter region of the poly(ADP-ribose) polymerase gene has been isolated using a Sau3AI genomic library derived from human leukocyte. It lacks typical transcriptional regulatory elements such as TATA and CAAT boxes, but it contains two potential Sp1 binding sites and three putative AP-2 binding elements. The region up to nucleotide position-99 in relation to the predominant transcriptional initiation site exhibits promoter activity as judged by chloramphenicol acetyltransferase assay and the activity is enhanced both by cAMP and by phorbol ester. Northern blot and Western blot analyses have revealed that expression of the polymerase gene is also stimulated by both of these compounds in cultured HeLa cells. Southern blot hybridization of genomic DNA separately digested with various endonucleases gives a discrete single band in each case when the 5'-untranslated region of the polymerase cDNA is used as a probe. These results indicate that poly(ADP-ribose) polymerase is encoded by a unique gene whose expression is regulable by cAMP and by phorbol ester.
Linear Programming and Network Flows (1978)

One: Introduction.Two: Linear Algebra, Convex Analysis, and Polyhedral Sets.Three: The Simplex Method.Four: Starting Solution and Convergence.Five: Special Simplex Implementations and Optimality Conditions.Six: Duality and Sensitivity Analysis.Seven: The Decomposition Principle.Eight: Complexity of the Simplex Algorithms.Nine: Minimal-Cost Network Flows.Ten: The Transportation and Assignment Problems.Eleven: The Out-of-Kilter Algorithm.Twelve: Maximal Flow, Shortest Path, Multicommodity Flow, and Network Synthesis Problems.Bibliography.Index.
Human Ect2 Is an Exchange Factor for Rho Gtpases, Phosphorylated in G2/M Phases, and Involved in Cytokinesis (1999)

Animal cells divide into two daughter cells by the formation of an actomyosin-based contractile ring through a process called cytokinesis. Although many of the structural elements of cytokinesis have been identified, little is known about the signaling pathways and molecular mechanisms underlying this process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTPases, RhoA, Rac1, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other known guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nuclear localization in interphase, spreads throughout the cytoplasm in prometaphase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH(2)-terminal domain required for the midbody localization but lacking the COOH-terminal catalytic domain, strongly inhibits cytokinesis. Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis. These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division.
Electrical Characteristics and Chemical Stability of Non-Oxidized, Methyl-Terminated Silicon Nanowires (2006)

Silicon nanowires (Si NWs) modified by covalent Si-CH3 functionality, with no intervening oxide, show atmospheric stability, high conductance values, low surface defect levels, and allow for the formation of air-stable Si NW Field-Effect Transistors (FETs) having on-off ratios in excess of 105 over a relatively small gate voltage swing (+/-2 V).
LEDGF1-326 Decreases P23H and Wild Type Rhodopsin Aggregates and P23H Rhodopsin Mediated Cell Damage in Human Retinal Pigment Epithelial Cells (2011)

P23H rhodopsin as well as WT rhodopsin form aggregates in RPE cells and LEDGF(1-326) decreases these aggregates. Further, LEDGF(1-326) reduces the RPE cell damage caused by P23H rhodopsin. LEDGF(1-326) might be useful in treating cellular damage associated with protein aggregation diseases such as retinitis pigmentosa.
European Data Directory (2011)

This directory signposts key statistics and data collections for Europe as a whole and individual European countries which include data relating to children's, young people's and maternal health.
Differential Expression and Function of Two Homologous Subunits of Yeast 1,3-β-D-Glucan Synthase (1995)

1,3-beta-D-Glucan is a major structural polymer of yeast and fungal cell walls and is synthesized from UDP-glucose by the multisubunit enzyme 1,3-beta-D-glucan synthase. Previous work has shown that the FKS1 gene encodes a 215-kDa integral membrane protein (Fks1p) which mediates sensitivity to the echinocandin class of antifungal glucan synthase inhibitors and is a subunit of this enzyme. We have cloned and sequenced FKS2, a homolog of FKS1 encoding a 217-kDa integral membrane protein (Fks2p) which is 88% identical to Fks1p. The residual glucan synthase activity present in strains with deletions of fks1 is (i) immunodepleted by antibodies prepared against FKS2 peptides, demonstrating that Fks2p is also a component of the enzyme, and (ii) more sensitive to the echinocandin L-733,560, explaining the increased sensitivity of fks1 null mutants to this drug. Simultaneous disruption of FKS1 and FKS2 is lethal, suggesting that Fks1p and Fks2p are alternative subunits with essential overlapping function. Analysis of FKS1 and FKS2 expression reveals that transcription of FKS1 is regulated in the cell cycle and predominates during growth on glucose, while FKS2 is expressed in the absence of glucose. FKS2 is essential for sporulation, a process which occurs during nutritional starvation. FKS2 is induced by the addition of Ca2+ to the growth medium, and this induction is completely dependent on the Ca2+/calmodulin-dependent phosphoprotein phosphatase calcineurin. We have previously shown that growth of fks1 null mutants is highly sensitive to the calcineurin inhibitors FK506 and cyclosporin A. Expression of FKS2 from the heterologous ADH1 promoter results in FK506-resistant growth. Thus, the sensitivity of fks1 mutants to these drugs can be explained by the calcineurin-dependent transcription of FKS2. Moreover, FKS2 is also highly induced in response to pheromone in a calcineurin-dependent manner, suggesting that FKS2 may also play a role in the remodeling of the cell wall during the mating process.
Three-dimensional imaging techniques: A literature review (2014)

Imaging is one of the most important tools for orthodontists to evaluate and record size and form of craniofacial structures. Orthodontists routinely use 2-dimensional (2D) static imaging techniques, but deepness of structures cannot be obtained and localized with 2D imaging. Three-dimensional (3D) imaging has been developed in the early of 1990's and has gained a precious place in dentistry, especially in orthodontics. The aims of this literature review are to summarize the current state of the 3D imaging techniques and to evaluate the applications in orthodontics.
Tumor Stress-Induced Phosphoprotein1 (STIP1) as a Prognostic Biomarker in Ovarian Cancer (2013)

Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore ≥169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; P<0.0001). Moreover, STIP1 histoscores were significantly higher in high-grade tumors (grade 3) than in low-grade (grade 1-2) malignancies (P<0.0001), suggesting that STIP1 may be a proxy for tumor aggressiveness. The results of multivariable analysis revealed that high STIP1 histoscores, advanced stages, histologic types, and the presence of residual disease (≥2 cm) were independent predictors of poor prognosis. The addition of STIP1 histoscores improved the prediction of overall and progression-free survival rates in the multivariable Cox proportional hazard model. The treatment of ovarian cancer cells with recombinant STIP1 stimulated cell proliferation and migration, but co-treatment with anti-STIP1 antibodies abrogated this effect. Our findings suggest that STIP1 expression may be related to prognosis and that the STIP1 pathway may represent a novel therapeutic target for human ovarian cancer.
Production of normal mice from oocytes fertilized and developed without zonae pellucidae (1992)

Mouse oocytes, freed from zonae pellucidae, were inseminated and cultured in vitro. When inseminated with a modest concentration of spermatozoa (approximately 5/microliter), 79% of 151 oocytes were fertilized normally, of which the majority developed into blastocysts. When 177 blastocysts were transferred to 12 pseudopregnant foster mothers, 10 (83%) of the mothers became pregnant and 37 live pups were obtained. Although the overall rate of development of zona-free embryos was slightly inferior to that of zona-intact (control) embryos, these results nevertheless indicate that the oocyte and embryo are potentially capable of normal fertilization and development in the total absence of the native zona pellucida. Since the acrosome reaction is essential for successful sperm-oocyte fusion, zona-free oocytes must have been fertilized by spermatozoa which had undergone the reaction either in the medium or on the surface of the oocyte plasma membrane. Such acrosome reactions, which are not mediated by the native zona pellucida, can be called 'unphysiological' or 'spurious' but the spermatozoa with such reactions were certainly functional, as they produced healthy offspring.
Tissue Engineering's Impact on Dentistry (2001)

Tissue engineering is a novel and exciting field that aims to re-create functional, healthy tissues and organs in order to replace diseased, dying, or dead tissues. The field has developed due to the inadequate supply of organs and tissues for patients requiring organ and tissue replacement. The following review first describes three major tissue engineering strategies. Although similar in their objectives, these strategies each maintain a unique component. Next, several examples of preclinical and clinical progress engineering oral-maxillofacial tissues are presented. Each of these examples highlights specific tissue engineering applications to different tissues of the oral-maxillofacial apparatus. Finally, practical implications are addressed as well as challenges that must be met in order for tissue engineering to reach its full potential.
Limited plasticity of mesenchymal stem cells cocultured with adult cardiomyocytes (2006)

In order to assess, in a controlled in vitro model, the differentiation potential of adult bone marrow derived stem cells we have developed a coculture procedure using adult rat cardiomyocytes and mesenchymal stem cells (MSCs) from transgenic GFP positive rats. We investigated in the cocultured MSCs the time course of cellular processes that are difficult to monitor in in vivo experiments. Adult rat cardiomyocytes and adult rat MSCs were cocultured for up to 7 days and analyzed by confocal microscopy. Several markers were studied by immunofluorescence technique. The fluorescent ST-BODIPY-Dihydropyridine was used to label calcium channels in living cells. Intracellular calcium was monitored with the fluorescent probe X-Rhod-1. Immunofluorescence experiments showed the presence of connexin-43 between cardiomyocytes and MSCs and between MSCs, while no sarcomeric structures were observed at any time of the coculture. We looked at the expression of calcium channels and development of voltage-dependent calcium signaling in cocultured MSCs. MSCs showed a time-dependent increase of labeling of ST-BODIPY-Dihydropyridine, reaching a relatively strong level after 72 h of coculture. The treatment with a non-fluorescent DHP, Nifedipine, completely abolished ST-BODIPY labeling. We investigated whether depolarization could modulate intracellular calcium. Depolarization-induced calcium transients increased in MSCs in relation to the coculture time. We conclude that MSCs cocultured with adult cardiomyocytes present preliminary evidence of voltage-dependent calcium modulation uncoupled with the development of nascent or adult myofibrils, thus showing a limited lineage specification and a low plasticity to differentiate in a full cardiomyocyte-like phenotype.
The Golgi Sialoglycoprotein MG160, Expressed in Pichia pastoris, Does Not Require Complex Carbohydrates and Sialic Acid for Secretion and Basic Fibroblast Growth Factor Binding (1997)

MG160, a type I membrane sialoglycoprotein of the medial cisternae of the rat Golgi apparatus, shows high homology (over 90%) with CFR, a fibroblast growth factor receptor, and ESL-1, an E-selectin ligand of the cell surface of murine myeloid cells. When Chinese Hamster Ovary (CHO) cells were stably transfected with a cDNA lacking the transmembrane and C-terminus cytoplasmic domain of MG160 (delta TMCT), a fully processed protein of 160 kDa apparent molecular mass was recovered in the culture medium. When these cells were treated with tunicymycin, a 130- to 140-kDa protein was immunoprecipitated from the culture medium. A construct lacking the signal sequence, the single transmembrane, and the cytoplasmic domains of MG160 (delta TMCT-) was integrated at the HIS Pichia pastoris genome site using the expression vector pPIC 9 which possesses a yeast compatible signal sequence (Invitrogen). Recombinant protein accumulated in the medium to approximately 10 mg/L. The yeast recombinant protein lacked complex carbohydrates and sialic acid but bound 125I bFGF. Similarly, rat MG160 subjected to deglycosylation by peptide:N-glycosidase F (PNGase) bound 125I bFGF.
Hepatocyte Nuclear Factor-1α, GATA-4, and Caudal Related Homeodomain Protein Cdx2 Interact Functionally to Modulate Intestinal Gene Transcription (2002)

Sucrase-isomaltase (SI), an intestine-specific gene, is induced in the differentiated small intestinal villous epithelium during the suckling-weaning transition in mice. We have previously identified cis-acting elements within a short evolutionarily conserved SI promoter. However, the nature and profile of expression of the interacting proteins have not been fully characterized during this developmental transition. Herein, we show that hepatocyte nuclear factor-1 alpha (HNF-1 alpha), GATA-4, and caudal related homeodomain proteins Cdx2 and Cdx1 are the primary transcription factors from the adult mouse intestinal epithelium to interact with the SIF3, GATA, and SIF1 elements of the SI promoter. We wanted to study whether HNF-1 alpha, GATA-4, and Cdx2 can cooperate in the regulation of SI gene expression. Immunolocalization experiments revealed that HNF-1 alpha is detected in rare epithelial cells of suckling mice and becomes progressively more expressed in the villous epithelial cells during the suckling-weaning transition. GATA-4 protein is expressed exclusively in villous differentiated epithelial cells of the proximal small intestine, decreases in expression in the ileum, and becomes undetectable in the colon. HNF-1 alpha, GATA-4, and Cdx2 interact in vitro and in vivo. These factors activate SI promoter activity in cotransfection experiments where GATA-4 requires the presence of both HNF-1 alpha and Cdx2. These findings imply a combinatory role of HNF-1 alpha, Cdx2, and GATA-4 for the time- and position-dependent regulation of SI transcription during development.
Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test (1997)

The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 microgram and gabapentin at 300 micrograms produced significant antinociception. Pretreatment with spinal gabapentin at 300 micrograms shifted the dose-response curve of spinal morphine to the left with a decrease in morphine ED50 value from 1.06 micrograms to 0.34 microgram. The antinociceptive effects produced by the combination of a subantinociceptive dose of morphine and gabapentin were reversed by spinal naloxone at 30 micrograms but were not reversed by spinal bicuculline at 0.3 microgram. Furthermore, the concurrent administration of spinal naloxone at 30 micrograms with the combination of morphine and gabapentin blocked antinociception, while the concurrent administration of spinal bicuculline at 0.3 microgram failed to prevent antinociception. These results indicate that the combination of spinal gabapentin and morphine produces an enhancement of antinociception that appears to involve the spinal mu opioid receptors. Furthermore, repeated administration of gabapentin for 3 days did not affect the enhancing effect of gabapentin on the antinociceptive effect of morphine, indicating that tolerance did not develop to gabapentin's ability to enhance morphine antinociception.