gebhart/patrepeval huggingface dataset:
Distal regulatory elements from the mouse metallothionein locus stimulate gene expression in transgenic mice. (1993)

DNA regions of 10 and 7 kb that flank the mouse metallothionein II (MT-II) and MT-I genes, respectively, were combined with a minimally marked MT-I (MT-I*) gene and tested in transgenic mice. This construct resulted in (i) position-independent expression of MT-I* mRNA and copy number-dependent expression, (ii) levels of hepatic MT-I mRNA per cell per transgene that were about half that derived from endogenous MT-I genes, (iii) appropriate regulation by metals and hormones, and (iv) tissue distribution of transgene mRNA that resembled that of endogenous MT-I mRNA. These features were not observed when MT-I* was tested without the flanking regions. These MT-I flanking sequences also improved the expression of rat growth hormone reporter genes, with or without introns, that were under the control of the MT-I promoter. Moreover, they enhanced expression from two of four heterologous promoters/enhancers that were tested. Deletion analysis indicated that regions known to have DNase I-hypersensitive sites were necessary but not sufficient for high-level expression. These data suggest that the DNA regions flanking the mouse MT-I and MT-II genes have functions like the locus control regions described for other genes.
Rheological action of drugs that prevent erythrocyte dehydration. (1991)

The water content of the human erythrocyte is a major determinant of its cytoplasmic viscosity and thus deformability. Loss of cell water may be either primary or secondary to loss of erythrocyte cations (K+). Several existing drugs (cetiedil citrate, pentoxifylline and piracetam) have recently been shown to inhibit K+ loss from erythrocytes and thus have the potential to prevent erythrocyte dehydration. Further studies of cation flux pathways in the erythrocyte membrane are of importance for the development of new drugs that maintain cell hydration.
PEYZAJ MATRİS, YAMA VE KORİDORLARININ VEJETASYON FORMASYONLARINDAKİ FARKLILIKLARA DAYANARAK BELİRLENMESİNE YÖNELİK BİR ARAŞTIRMA: KAZDAĞI MİLLİ PARKI ÖRNEĞİ (2011)

Bu calisma kapsaminda bir peyzaj mozagini olusturan; peyzaj matrisi, yama ve koridor unsurlari ele alinmistir. Bu temel unsurlari belirlerken de vejetasyon analizi calismalari esas alinmistir. Bilindigi uzere Kazdagi Milli Parki, peyzaj matrisi olarak dogal bir ormandir. Calisma alaninda 4 farkli peyzaj yamasi olarak niteleyebilecegimiz; ormanici acikliklar, yuksek dag cayirlari, yapay yamalar olarak tarim alanlari ile (zeytinlikler ve meyvelikler) saf veya karisik halde mescerelerin hakim oldugu yamalar bulunmaktadir. Ayrica 2 farkli peyzaj koridoru olarak nitelendirebilcegimiz; akarsu yataklari ile yollar yer almaktadir. Dogal orman matrisi icerisinde yer alan yama ve koridorlarin belirlenmesinde 2006-2008 yillari arasinda saha calismalari kapsaminda gerceklestirilen vejetasyon calismalari esas alinmistir. Vejetasyon analizi calismalari sonucuna gore belirlenen farkli vejetasyon formasyonlari; farkli peyzaj yama ve koridorlarinin tespitine imkan saglamistir.
Insulin-like Growth Factor-independent Effects Mediated by a C-terminal Metal-binding Domain of Insulin-like Growth Factor Binding Protein-3 (2003)

Insulin-like growth factors (IGFs) play a central role in the integration of proliferative and survival responses of most mammalian cell types. IGF-binding protein-3 (IGFBP-3) influences IGF action directly as a carrier of IGFs but also modulates these actions indirectly via independent mechanisms involving interactions with plasma, extracellular matrix and cell surface molecules, conditional proteolysis, cellular uptake, and nuclear transport. Here we demonstrate that a short C-terminal metal-binding domain (MBD) of IGFBP-3 mediates binding to metals. MBD epitopes, sequestered in the intact molecule, are unmasked by incubation in the presence of ferrous (but not ferric or zinc) ions. An isolated 14-mer MBD peptide triggered apoptotic effects in stressed HEK293 cells as effectively as IGFBP-3. The MBD, which encompasses a nuclear localization sequence and an adjacent putative caveolin-binding sequence, mobilizes rapid cellular uptake and nuclear localization of unrelated proteins such as green fluorescent protein and streptavidin-horseradish peroxidase conjugate. Metal ions stimulate MBD-mediated cellular/nuclear uptake in vivo. Cross-linking studies showed a direct physical interaction of MBD with integrins alphav and beta1, caveolin-1, and transferrin receptor. MBD-mediated protein mobilization and pro-apoptotic effects are inhibited by nystatin but not chlorpromazine, suggesting an involvement of caveolar-mediated endocytosis. However, MBD effects are inhibited by antibodies to transferrin receptor or integrins. These results are discussed with particular reference to the cell target specificity of IGFBP-3 in disease processes such as cancer and atherosclerosis.
Prognostic Significance of Histopathologic Subsets in Idiopathic Pulmonary Fibrosis (1998)

Idiopathic pulmonary fibrosis (IPF) is a generally fatal disorder with a reported median survival of 3 to 6 yr. This has been based on relatively few studies with diagnoses inconsistently confirmed by adequate lung biopsy. Retrospective analysis of 104 patients with IPF who had open lung biopsy (OLB) at Mayo Medical Center from 1976 to 1985 was performed to establish the overall survival rate, the spectrum of histopathological subgroups and their associated prognostic significance. The study group consisted of 54 men and 50 women with a median age of 63 yr. Median survival was 3.8 yr after diagnosis by OLB with an estimated 10 yr survival of 27%. Current histopathologic review showed a heterogeneous group including usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), nonspecific interstitial pneumonia/fibrosis (NSIP), acute interstitial pneumonia (AIP), bronchiolitis, bronchiolitis obliterans organizing pneumonia (BOOP), and others. Median survival of the UIP group was 2.8 yr which is significantly worse (p < 0.001) than for other subgroups of chronic interstitial pneumonias. IPF includes several histopathologic subgroups with significantly different survival rates. Patients with UIP have worse survival than patients with other types of idiopathic chronic interstitial pneumonias including NSIP. Accurate histopathologic classification is essential for prognostication in patients with IPF.
Insider Threat Detection Using a Graph-Based Approach (2010)

The authors present the use of graph-based approaches to discovering anomalous instances of structural patterns in data that represent insider threat activity. The approaches presented search for activities that appear to match normal transactions, but in fact are structurally different. The authors show the usefulness of applying graph theoretic approaches to discovering suspicious insider activity in domains such as social network communications, business processes, and cybercrime. The authors present some performance results to show the effectiveness of our approaches, and then conclude with some ongoing research that combines numerical analysis with structure analysis, analyzes multiple normative patterns, and extends to dynamic graphs.
Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies (2009)

Sequential administration of DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors has demonstrated clinical efficacy in patients with hematologic malignancies. However, the mechanism behind their clinical efficacy remains controversial. In this study, the methylation dynamics of 4 TSGs (p15(INK4B), CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marrow samples from 30 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who completed a minimum of 4 cycles of therapy with 5-azacytidine and entinostat. Reversal of promoter methylation after therapy was observed in both clinical responders and nonresponders across all genes. There was no association between clinical response and either baseline methylation or methylation reversal in the bone marrow or purified CD34(+) population, nor was there an association with change in gene expression. Transient global hypomethylation was observed in samples after treatment but was not associated with clinical response. Induction of histone H3/H4 acetylation and the DNA damage-associated variant histone gamma-H2AX was observed in peripheral blood samples across all dose cohorts. In conclusion, methylation reversal of candidate TSGs during cycle 1 of therapy was not predictive of clinical response to combination "epigenetic" therapy. This trial is registered with http://www.clinicaltrials.gov under NCT00101179.
Identification and Characterization of a Bovine Neurite Growth Inhibitor (bNI-220) (1998)

The poor axonal regeneration that follows lesions of the central nervous system (CNS) is crucially influenced by the local CNS tissue environment through which neurites have to grow. In addition to an inhibitory role of the glial scar, inhibitory substrate effects of CNS myelin and oligodendrocytes have been demonstrated. Several proteins including NI-35/250, myelin-associated glycoprotein, tenascin-R, and NG-2 have been described to have neurite outgrowth inhibitory or repulsive properties in vitro. Antibodies raised against NI-35/250 (monoclonal antibody IN-1) were shown to partially neutralize the growth inhibitory effect of CNS myelin and oligodendrocytes, and to result in long distance fiber regeneration in the lesioned adult mammalian CNS in vivo. We report here the purification of a myelin protein to apparent homogeneity from bovine spinal cord which exerts a potent neurite outgrowth inhibitory effect on PC12 cells and chick dorsal root ganglion cells, induces collapse of growth cones of chick dorsal root ganglion cells, and also inhibits the spreading of 3T3 fibroblasts. These activities could be neutralized by the monoclonal antibody IN-1. The purification procedure includes detergent solubilization, anion exchange chromatography, gel filtration, and elution from high resolution SDS-polyacrylamide gel electrophoresis. The active protein has a molecular mass of 220 kDa and an isoelectric point between 5.9 and 6.2. Its inhibitory activity is sensitive to protease treatment and resists harsh treatments like 9 M urea or short heating. Glycosylation is, if present at all, not detectable. Microsequencing resulted in six peptides and strongly suggests that this proteins is novel.
Effects of trazodone on aggressive behavior in seven patients with organic mental disorders (1988)

Seven patients with organic mental disorders and physically aggressive behavior were treated with trazodone. Three ceased demonstrating aggressive behavior within 4-6 weeks after starting trazodone treatment. Three had no discernible reduction in aggressiveness. One was unable to complete the trial.
HMGA1 Drives Metabolic Reprogramming of Intestinal Epithelium during Hyperproliferation, Polyposis, and Colorectal Carcinogenesis (2015)

Although significant progress has been made in the diagnosis and treatment of colorectal cancer (CRC), it remains a leading cause of cancer death worldwide. Early identification and removal of polyps that may progress to overt CRC is the cornerstone of CRC prevention. Expression of the High Mobility Group A1 (HMGA1) gene is significantly elevated in CRCs as compared with adjacent, nonmalignant tissues. We investigated metabolic aberrations induced by HMGA1 overexpression in small intestinal and colonic epithelium using traveling wave ion mobility mass spectrometry (TWIMMS) in a transgenic model in which murine Hmga1 was misexpressed in colonic epithelium. To determine if these Hmga1-induced metabolic alterations in mice were relevant to human colorectal carcinogenesis, we also investigated tumors from patients with CRC and matched, adjacent, nonmalignant tissues. Multivariate statistical methods and manual comparisons were used to identify metabolites specific to Hmga1 and CRC. Statistical modeling of data revealed distinct metabolic patterns in Hmga1 transgenics and human CRC samples as compared with the control tissues. We discovered that 13 metabolites were specific for Hmga1 in murine intestinal epithelium and also found in human CRC. Several of these metabolites function in fatty acid metabolism and membrane composition. Although further validation is needed, our results suggest that high levels of HMGA1 protein drive metabolic alterations that contribute to CRC pathogenesis through fatty acid synthesis. These metabolites could serve as potential biomarkers or therapeutic targets.
Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. (1994)

By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.
Efficient nonmeiotic allele introgression in livestock using custom endonucleases (2013)

We have expanded the livestock gene editing toolbox to include transcription activator-like (TAL) effector nuclease (TALEN)- and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into horned bull fibroblasts. Single nucleotide alterations or small indels were introduced into 14 additional genes in pig, goat, and cattle fibroblasts using TALEN mRNA and oligonucleotide transfection with efficiencies of 10-50% in populations. Several of the chosen edits mimic naturally occurring performance-enhancing or disease- resistance alleles, including alteration of single base pairs. Up to 70% of the fibroblast colonies propagated without selection harbored the intended edits, of which more than one-half were homozygous. Edited fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC genes to model infertility and colon cancer. Our methods enable unprecedented meiosis-free intraspecific and interspecific introgression of select alleles in livestock for agricultural and biomedical applications.
Protein kinase C mediates human neutrophil cytotoxicity (1987)

Human neutrophils stimulated with phorbol myristate acetate were able to damage human erythroleukemic K562 cells, in the absence of specific antibody, as assessed by a two hour 51Cr release assay. Neutrophils treated with formyl-peptide fMet-Leu-Phe did not display tumoricidal response, but the addition of diacylglycerol kinase inhibitor R59022 together with formyl-peptide induced the cytotoxic capacity against tumor target cells. Phorbol ester is a potent activator of certain functions of neutrophils because of its ability to directly and irreversibly stimulate protein kinase C; formyl-peptide, on the contrary, activates protein kinase C by inducing a rapid and transient production of diacylglycerol, that is quickly metabolized. The addition of an inhibitor of diacylglycerol kinase, R59022, however potentiated the action of formyl-peptide. These results indicate that protein kinase C is involved in the tumoricidal activity of neutrophils against K562 cells, and that maximal activation of the enzyme is required to achieve the cytotoxic response.
Centralized Administration of Distributed Firewalls (1996)

Allowing the connection of various networks to one's internal network while keeping the internal network protected from unauthorized access is key to success in this information age. Firewall systems are currently the best known way of achieving this objective. Management of these firewalls in a secure, consistent and reliable manner is a strategy that is imperative to the successful interconnection of diverse networks. This paper describes the technical implementation of a paradigm enabling the administration of distributed firewall systems from a centralized location.
Physicochemical and biological characterization of asialoerythropoietin (1990)

Various partially or fully desialylated human erythropoietins were obtained by neuraminidase digestion of the hormone, without non-specific proteolysis and degradation of carbohydrates. Asialoerythropoietin showed a specific activity of 220-IU/mg protein in vivo, although that of the intact erythropoietin was 2.2 x 10(5) IU/mg. A linear relationship was found between the logarithm of the specific activity in vivo and the number of sialic acids. The asialoerythropoietin showed a four-times-higher specific activity in vitro compared with intact erythropoietin using mouse bone marrow cells. It also showed an approximately six-times-higher specific activity in a colony-forming assay for the erythroid colony-forming unit and the erythroid burst-forming unit. Partially or fully de-N-glycosylated erythropoietin derivatives also showed lower in vivo activity but higher in vitro activity than the intact erythropoietin, dependent on the number of sialic acids. To clarify the reason for the enhanced biological activity of asialoerythropoietin in vitro, the binding of intact 125I-erythropoietin or 125I-asialoerythropoietin to cells containing specific receptors for the hormone was analyzed. 125I-asialoerythropoietin bound to spleen cells from anemic mice approximately five times faster than did intact 125I-erythropoietin. The amount of 125I-asialoerythropoietin internalized by target cells, measured in the absence of NaN3, was four times higher than that of intact erythropoietin. These results demonstrate that asialoerythropoietin binds to its receptor faster than the intact form. This may be the main reason for the increased activity of asialoerythropoietin in vitro.
Precomputed shadow fields for dynamic scenes (2005)

We present a soft shadow technique for dynamic scenes with moving objects under the combined illumination of moving local light sources and dynamic environment maps. The main idea of our technique is to precompute for each scene entity a shadow field that describes the shadowing effects of the entity at points around it. The shadow field for a light source, called a source radiance field (SRF), records radiance from an illuminant as cube maps at sampled points in its surrounding space. For an occluder, an object occlusion field (OOF) conversely represents in a similar manner the occlusion of radiance by an object. A fundamental difference between shadow fields and previous shadow computation concepts is that shadow fields can be precomputed independent of scene configuration. This is critical for dynamic scenes because, at any given instant, the shadow information at any receiver point can be rapidly computed as a simple combination of SRFs and OOFs according to the current scene configuration. Applications that particularly benefit from this technique include large dynamic scenes in which many instances of an entity can share a single shadow field. Our technique enables low-frequency shadowing effects in dynamic scenes in real-time and all-frequency shadows at interactive rates.
Presumptive meanings: The theory of generalized conversational implicature (2000)

From the Publisher:
When we speak, we mean more than we say. In this book Stephen C. Levinson explains some general processes that underlie presumptions in communication. This is the first extended discussion of preferred interpretation in language understanding, integrating much of the best research in linguistic pragmatics from the last two decades. Levinson outlines a theory of presumptive meanings, or preferred interpretations, governing the use of language, building on the idea of implicature developed by the philosopher H. P. Grice. Some of the indirect information carried by speech is presumed by default because it is carried by general principles, rather than inferred from specific assumptions about intention and context. Levinson examines this class of general pragmatic inferences in detail, showing how they apply to a wide range of linguistic constructions. This approach has radical consequences for how we think about language and communication.
The Electrochemical Reaction of Li with Amorphous Si-Sn Alloys (2003)

samples for were prepared by magnetron sputtering using a combinatorial materials science approach. The room-temperature resistivity and X-ray diffraction (XRD) patterns of the samples were used to select materials having both an amorphous structure and good conductivity for further study. The reaction of lithium with amorphous was then studied by electrochemical methods and by in situ XRD. The electrode material apparently remains amorphous throughout all portions of the charge and discharge profile, in the range in No crystalline phases are formed, unlike the situation when lithium reacts with tin. Using the Debye scattering formalism, we show that the XRD patterns of the a- starting material and can be explained by the same local atomic arrangements as found in crystalline Si and Si or Sn, respectively. In fact, the in situ XRD patterns of a- for any x, can be well approximated by a linear combination of the patterns for and This suggests that predominantly only two local environments for Si and Sn are found at any value of x in However, based on differential capacity vs. potential results for Li/a- there is no evidence for two-phase regions during the charge and discharge profile. Thus, the two local environments must appear at random throughout the particles. We speculate that the charge-discharge hysteresis in the voltage-capacity profile of cells is caused by the energy dissipated during the changes in the local atomic environment around the host atoms. © 2002 The Electrochemical Society. All rights reserved.
Analysis and compensation for nonlinear interference of two high-order modulation carriers over satellite link (2010)

We introduce analytical characterization of the nonlinear interference that results when passing more than one high-order modulation carrier through the same nonlinear transponder high-power amplifier (HPA). A Volterra filter is proposed which is novel in its implementation of this analytical characterization and modeling of intersymbol interference (ISI) and adjacent channel interference (ACI). Our focus is on adaptive algorithms with pilot-based training so that the solutions are completely blind to unknown transponder HPA characteristics, and can rapidly respond to varying operating back-off level. Furthermore, two families of adaptive solutions are provided to compensate for nonlinear ISI and ACI. The first set performs adaptive channel inversion and then applies equalization. The second set of solutions performs adaptive channel identification and then applies cancellation. The effectiveness of the proposed analysis and techniques is demonstrated via extensive simulations for high-order QAM and APSK modulations. Also included is the coded performance with selected LDPC codes designed for the DVB-S2 standard. Finally, computational complexity is assessed and performance impact is quantified when complexity is reduced by decreasing the number of Volterra coefficients.