gebhart/patrepeval huggingface dataset:
Stimulatory Effect of Human, but not Bovine, Growth Hormone Expression on Numbers of Tuberoinfundibular Dopaminergic Neurons in Transgenic Mice (1997)

Mice transgenic for heterologous and ectopic GH expression serve as models for studying the feedback effects of elevated nonregulated GH on hypothalamic hypophysiotropic neurons as well as on peripheral function. For example, hypothalamic somatostatin expression has been shown to be increased markedly in mice bearing either bovine (b) or human (h) GH transgenes. Human, but not bovine, GH has lactogenic properties in mice, and appears to stimulate PRL-inhibiting tuberoinfundibular dopaminergic (TIDA) neurons. The present study was designed to determine the effect of a lifelong excess of hGH on dopamine (DA) expression in and numbers of TIDA neurons. Male mice of four transgenic lines were examined. The transgenic animals bore constructs of either bGH or hGH fused to either metallothionein (MT) or phosphoenolpyruvate carboxykinase (PEPCK) promoters; brains of transgenic mice were compared morphologically with those of nontransgenic littermates. Formaldehyde-induced catecholamine histofluorescence and tyrosine hydroxylase (TH) immunocytochemistry were examined in alternate brain sections; cell number was quantified for TIDA neurons (area A12) and a nonhypophysiotropic diencephalic DA area, the medial zona incerta (A13). Body weights were higher (P < 0.01) in PEPCK-GH than in MT-GH transgenic mice, as were serum levels of heterologous GH in those lines. In MT-hGH, but not MT-bGH or PEPCK-bGH, transgenic mice, A12 perikaryal fluorescence was enhanced, and ME fluorescence was reduced compared with those in control animals. The reduced ME DA is likely to reflect stimulation of TIDA neurons, because A12 TH-immunoreactive neuron number was increased by 34% in MT-hGH mice compared with that in controls (P < 0.05). In mice bearing the PEPCK-hGH construct, A12 TH neuron number was increased 47% (P < 0.001) compared with that in littermate controls. There were no differences in A13 cell number among animals, and A12 cell numbers in mice expressing bGH did not differ from control values. These results suggest that although extremely high levels of circulating bGH do not stimulate TIDA neurons, lifelong high levels of hGH have a stimulatory and graded effect on developmental differentiation of these cells for TH and DA production, supporting the concept of PRL as a trophic factor for TIDA neurons.
Selective Nanopatterning Using Citrate-Stabilized Au Nanoparticles and Cystein-Modified Amphiphilic Protein (2009)

We present an approach where biomolecular self-assembly is used in combination with lithography to produce patterns of metallic nanoparticles on a silicon substrate. This is achieved through a two-step method, resulting in attachment of nanoparticles on desired sites on the sample surfaces, which allowed a detailed characterization. First, a genetically modified hydrophobin protein, NCysHFBI, was attached by self-assembly on a hydrophobic surface or a surface patterned with hydrophobic and hydrophilic domains. The next step was to label the protein layers with 17.8 nm gold nanoparticles, to allow microscopic characterization of the films. Kinetics and extent of attachment of nanoparticles were characterized by UV-vis spectroscopy and transmission electron microscopy. It was shown that the attachment of citrate-stabilized gold nanoparticles was strongly dependent on the electrostatic properties of the capping ligand layer and the density of nanoparticles in the monolayer could be controlled via pH. The resulting nanoparticle assemblies followed the original pattern created by optical lithography in high accuracy. We demonstrate that combining bottom-up and top-down nanotechnological approaches in a good balance can provide very effective ways to produce nanoscale components providing a functional interface between electronics and the biological world.
Gravel Packing Long Openhole Intervals with Viscous Fluids Utilizing High Gravel Concentrations: Toe-to-Heel Packing without the Need for Alternate Flow Paths (2009)

Abstract Openhole gravel packing is one of the most popular completion techniques, due to its high reliability along with the ability to deliver high-productivity wells. Currently, there are two techniques used for gravel placement, one utilizing low-viscosity carrier fluids and low gravel concentration. In this technique the gravel is placed in two waves commonly called Alpha/Beta packing. The second method utilizes a viscous carrier fluid and high concentrations of gravel in conjunction with alternative path screens which mitigate problems caused by unpredicted downhole events. In this paper we present a new approach for gravel packing long high angle openhole intervals without the need for alternative flow path screens but retaining the advantages of high gravel concentration slurries. This is supported by 2 field case histories from a field in India, where two gas wells were drilled with an oil-based drill-in fluid and gravel packed with a viscous water-based fluid. The packing mechanisms and efficiencies in these applications have been verified with downhole gauge analysis as well as mass balance calculations. Both wells are producing sand free with hydrocarbon production that met or exceeded operator expectations, with zero mechanical and extremely low rate dependent skins.
siRNA targeting of Cdx2 inhibits growth of human gastric cancer MGC-803 cells (2012)

Cdx2 was involved in regulating pro-gression of human gastric cancer cells MGC-803. Manipulation of Cdx2 expression may be a potential therapeutic strategy for gastric cancer.
<title>Accurate and efficient image-intensifier distortion-correction algorithm and its application in volume tomographic angiography</title> (1997)

An algorithm has been developed to correct the image distortion introduced by the image intensifier - CCD camera chain in our volume tomographic angiography imaging system. First the distorted image is partitioned into small quadrilateral regions, then each partition is mapped individually to the corrected image by its corresponding bilinear functions. The parameters of these bilinear functions can be acquired by a special calibration procedure and stored as a lookup table. The maximum errors before and after the distortion correction were measured to be 5.96 mm and 0.03 mm. The method is further applied to the 3D image reconstruction of a simulated vascular phantom and live animal studies.
Über Derivate des 1,3,4,5‐Tetrahydro‐2‐benzothiepin mit basischer Seitenkette in 1‐Stellung (1969)

Abstract β‐Diäthylaminoäthylchlorid reagiert mit 1‐Cyan‐1,3,4,5‐tetrahydro‐2‐benzothiepin (I) unter Bildung des Aminoäthylierungsproduktes IV und mit 1,3,4,5‐Tetrahydro‐2‐benzothiepin‐2,2‐dioxid (III) zum 1,1‐disubstituierten Derivat V.
Oligodeoxynucleotides containing palindrome sequences with internal 5'-CpG-3' act directly on human NK and activated T cells to induce IFN-gamma production in vitro. (1999)

Previous studies have shown that the action of bacterial or synthetic oligodeoxynucleotide (oligo-DNA) on mouse NK cells to produce IFN-gamma is mediated mostly by monocytes/macrophages activated by olig-DNA. However, its action on human IFN-gamma-producing cells has not been well investigated. In the present study, we examined the effect of oligo-DNAs on highly purified human NK and T cells. Bacillus Calmette-Guérin-derived or synthetic oligo-DNAs induced NK cells to produce IFN-gamma with an increased CD69 expression, and the autocrine IFN-gamma enhanced their cytotoxicity. The response of NK cells to oligo-DNAs was enhanced when the cells were activated with IL-2, IL-12, or anti-CD16 Ab. T cells did not produce IFN-gamma in response to oligo-DNAs but did respond independently of IL-2 when they were stimulated with anti-CD3 Ab. In the action of oligo-DNAs, the palindrome sequence containing unmethylated 5'-CpG-3' motif(s) appeared to play an important role in the IFN-gamma-producing ability of NK cells. The changes of base composition inside or outside the palindrome sequence altered its activity: The homooligo-G-flanked GACGATCGTC was the most potent IFN-gamma inducer for NK cells. The CG palindrome was also important for activated NK and T cells in their IFN-gamma production, although certain nonpalindromes acted on them. Among the sequences tested, cell activation- or cell lineage-specific sequences were likely; i.e., palindrome ACCGGT and nonpalindrome AACGAT were favored by activated NK cells but not by unactivated NK cells or activated T cells. These results indicate that oligo-DNAs containing CG palindrome act directly on human NK cells and activated T cells to induce IFN-gamma production.
Nucleocytoplasmic shuttling of oncoprotein Hdm2 is required for Hdm2-mediated degradation of p53 (1999)

The Hdm2 oncoprotein inhibits p53 functions by two means: (i) it blocks p53's transactivation activity and (ii) it targets p53 for degradation in a proteasome-dependent manner. Recent data indicate that Hdm2 shuttles between the nucleus and the cytoplasm and that the regulation of p53 levels by Hdm2 requires its nuclear export activity. Two different models are consistent with these observations. In the first, Hdm2 binds to p53 in the nucleus and shuttles p53 from the nucleus to the cytoplasm, and then it targets p53 to the cytoplasmic proteasome. Alternatively, Hdm2 and p53 could be exported separately from the nucleus and then associate in the cytoplasm, where Hdm2 promotes the degradation of p53. To distinguish between these two models, several Hdm2 mutants were employed. Hdm2NLS lacks the ability to enter the nucleus, whereas Hdm2NES is deficient in nuclear export. Hdm2NLS, Hdm2NES, or the combination of both mutants were unable to promote p53 degradation in the cotransfected 2KO cells (which were null for both the p53 and mdm2 genes), although wild-type Hdm2 efficiently reduced p53 levels under the same conditions. This observation is not a result of the differences in expression levels or stability between Hdm2 and these mutants. Moreover, coexpression of these mutants had no effect on wild-type Hdm-2-induced p53 destabilization. Thus, Hdm2 must shuttle p53 from the nucleus to the cytoplasm to target it for degradation in the cytoplasm.
The Effect of T Cell Growth Factor on the Generation of Cytolytic T Cells (1978)

The development of cytotoxic effector cells through primary allogeneic mixed tumor-lymphocyte culture (MTLC) was found to be accompanied by the production of T cell growth factor (TCGF). Addition of supplemental TCGF to MTLC resulted in the generation of significantly greater quantities of effector cells, and these effector cells displayed augmented cytotoxic activity. The TCGF-induced effect could not by duplicated by the addition of fresh medium or a mitogenic concentration of concananvalin A. Although TCGF augmented the proliferation of antigen-nonreactive cells, antigen-reactive cells appeared to be preferentially stimulated by TCGF. Finally, it was shown that depletion of TCGF from MTLC resulted in an impairment of proliferation and differentiation of cytotoxic effector cells. These findings demonstrate that soluble factors are involved in the regulation of in vitro cell-mediated immune responses in an analogous manner to similar factors that have been shown to regulate humoral immune responses. Therefore, the forces affecting TCGF production may modulate the amplitude of a T cell-mediated cytolytic response.
Epithelial-stromal interactions in normal and chemical carcinogen-treated adult bladder. (1977)

Summary Tumor formation in the adult rat urinary bladder may be induced by multiple intraurethral instillations of N -methyl- N -nitrosourea (MNU), and this bladder-chemical carcinogen system has been adapted for study of tissue interactive processes in neoplastic change. Responsiveness of transitional epithelium to stromal influences can be determined by scanning electron microscopic analysis of cell membrane changes on the luminal aspect of the urothelium in vivo and in long-term organ cultures (0 to 100 days in vitro ) of normal and chemical carcinogen-treated bladders and of homotypic and heterotypic recombinations of the isolated epithelial and stromal components from normal and MNU-treated bladders. Individual globular surface processes, their chain-like arrangement, and amalgamation to form the characteristic angular membrane of the superficial cell identify the cell surface maturation sequence of normal urothelium in vivo . This is reproduced in vitro but only where epithelium is in association with homotypic stroma. Absence of stoma leads to atypical epithelial cell differentiation, with numerous irregular microvilli of varying size and orientation patterning the cell surface; this implies epithelial dependence on stoma for normal cytodifferentiation. In MNU-induced benign and preneoplastic hyperplasia of the urothelium, short swollen microvilli cover the luminal surface, whereas surface differentiation of preneoplastic epithelium to overt neoplasia and tumor formation is associated with the appearance of increasingly complex and bizarre pleomorphic microvilli providing a convenient marker of cell abnormality. Production of pleomorphic microvilli is not reversed when neoplastic epithelium is placed in heterotypic combination with normal bladder stroma, suggesting epithelial independence of stromal influence. By contrast, abnormal pleomorphic microvilli develop on the surface of normal urothelium associated with stroma from MNU-treated bladder; this implies a stromal effect on the epithelium and suggests that MNU may elicit new epithelial behavior by causing a derangement of stromal function.
Generating Executable Capability Models for Requirements Validation (2012)

Executable modeling allows the models to be executed and treated as prototypes to determine the behaviors of a system. In this paper, we propose an approach for formalizing requirement models and generating executable models from them. Application activity diagrams (AADs), which are used to represent dynamic behaviors of systems in capability requirements models, are firstly formalized and saved as XML documents. Then, on the basis of these models, a mapping algorithm of translating AADs into instances of executable models for simulation is proposed. A case study is finally given to demonstrate the applicability of the method.
Highly Efficient Asymmetric Michael Addition of Aldehydes to Nitroalkenes Catalyzed by a Simple trans‐4‐Hydroxyprolylamide (2006)

Discriminating reactions: While no self-aldol reaction is observed in the reaction shown, catalyst 1 promotes the Michael addition of aldehydes to nitroalkenes with the lowest catalyst loading and lowest stoichiometric ratio of reactant aldehyde that have been reported so far for this type of reaction. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z602207_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Cochliobolus carbonum SNF1 Gene Is Required for Cell Wall–Degrading Enzyme Expression and Virulence on Maize (2000)

The production of cell wall-degrading enzymes (wall depolymerases) by plant pathogenic fungi is under catabolite (glucose) repression. In Saccharomyces cerevisiae, the SNF1 gene is required for expression of catabolite-repressed genes when glucose is limiting. An ortholog of SNF1, ccSNF1, was isolated from the maize pathogen Cochliobolus carbonum, and ccsnf1 mutants of HC toxin-producing (Tox2(+)) and HC toxin-nonproducing (Tox2(-)) strains were created by targeted gene replacement. Growth in vitro of the ccsnf1 mutants was reduced by 50 to 95% on complex carbon sources such as xylan, pectin, or purified maize cell walls. Growth on simple sugars was affected, depending on the sugar. Whereas growth on glucose, fructose, or sucrose was normal, growth on galactose, galacturonic acid, maltose, or xylose was somewhat reduced, and growth on arabinose was strongly reduced. Production of HC toxin was normal in the Tox2(+) ccsnf1 mutant, as were conidiation, conidial morphology, conidial germination, and in vitro appressorium formation. Activities of secreted beta-1,3-glucanase, pectinase, and xylanase in culture filtrates of the Tox2(+) ccsnf1 mutant were reduced by 53, 24, and 65%, respectively. mRNA expression was downregulated under conditions that induced the following genes encoding secreted wall-degrading enzymes: XYL1, XYL2, XYL3, XYL4, XYP1, ARF1, MLG1, EXG1, PGN1, and PGX1. The Tox2(+) ccsnf1 mutant was much less virulent on susceptible maize, forming fewer spreading lesions; however, the morphology of the lesions was unchanged. The Tox2(-) ccsnf1 mutant also formed fewer nonspreading lesions, which also retained their normal morphology. The results indicate that ccSNF1 is required for biochemical processes important in pathogenesis by C. carbonum and suggest that penetration is the single most important step at which ccSNF1 is required. The specific biochemical processes controlled by ccSNF1 probably include, but are not necessarily restricted to, the ability to degrade polymers of the plant cell wall and to take up and metabolize the sugars produced.
Protein-Tyrosine Kinase Inhibition: Mechanism-Based Discovery of Antitumor Agents (1992)

Protein-tyrosine kinases (PTKs) have been shown to induce the cascade of altered cell parameters characteristic of transformed cells. This proposition provides an important rationale for the discovery of potential antitumor agents from natural sources on the basis of inhibition of PTK activity. Numerous naturally occurring and synthetic analogues of PTK inhibitors were systematically evaluated in this review based on their structure-activity relationships and potential antitumor efficacy.
Silk Fibroin Conduits (2011)

Silk fibroin conduits were designed with appropriate porosity for peripheral nerve repair. The aim of this work was to use these conduits to examine cell inflammatory responses and functional recovery in a sciatic nerve defect model. A total of 45 randomized Lewis rats were used to create an 8-mm defect bridged by a silk guide, commercial collagen guide, or an autograft. After 1, 4, and 8 weeks, macrophage recruitment, percentage of newly formed collagen, number of myelinated axons, and gastrocnemius muscle mass were evaluated. Following 8 weeks, ED1+ cells in autograft and silk conduits decreased to <1% and 17% of week 1 values, respectively. Collagen formation revealed no difference for all measured time points, suggesting a similar foreign body response. Myelinated axon counts within the silk guide revealed a greater number of proximal spouts and distal connections than collagen guides. Gastrocnemius weights demonstrated a 27% decrease between silk and autografts after 8 weeks. This study demonstrates that, in addition to tailorable degradation rates, our silk conduits possess a favorable immunogenicity and remyelination capacity for nerve repair.
Prophylaxis with the Novel Immunomodulator Pidotimod Reduces the Frequency and Severity of Upper Respiratory Tract Infections in Children with Down's Syndrome (1999)

Down's syndrome (DS) is associated with several defects of both specific and non-specific immunity which may explain the enhanced susceptibility of DS subjects to viral and bacterial infections. In this study we have evaluated the effects of the new synthetic immunomodulator pidotimod in recurrent infections of the upper respiratory tract in a group of children with DS. It was an open trial vs untreated control, the pidotimod-treated group consisted of 14 subjects and the control group of 12. Pidotimod was administered at the dose of one 400 mg oral bottle/day for 90 days. There was a significant reduction in the frequency, severity and duration of infectious episodes in the pidotimod-treated group vs the untreated control group. The beneficial effects of pidotimod were also confirmed by a series of recordings made over the 90-day treatment period which showed a significant reduction in the number of days of fever, severity of the signs and symptoms of the acute episodes and use of antibiotics and antipyretic drugs. Pidotimod was well tolerated and no clinical, hematological or biochemical side-effects were noted.
GSK3β phosphorylation modulates CLASP–microtubule association and lamella microtubule attachment (2009)

Polarity of the microtubule (MT) cytoskeleton is essential for many cell functions. Cytoplasmic linker-associated proteins (CLASPs) are MT-associated proteins thought to organize intracellular MTs and display a unique spatiotemporal regulation. In migrating epithelial cells, CLASPs track MT plus ends in the cell body but bind along MTs in the lamella. In this study, we demonstrate that glycogen synthase kinase 3beta (GSK3beta) directly phosphorylates CLASPs at multiple sites in the domain required for MT plus end tracking. Although complete phosphorylation disrupts both plus end tracking and association along lamella MTs, we show that partial phosphorylation of the identified GSK3beta motifs determines whether CLASPs track plus ends or associate along MTs. In addition, we find that expression of constitutively active GSK3beta destabilizes lamella MTs by disrupting lateral MT interactions with the cell cortex. GSK3beta-induced lamella MT destabilization was partially rescued by expression of CLASP2 with mutated phosphorylation sites. This indicates that CLASP-mediated stabilization of peripheral MTs, which likely occurs in the vicinity of focal adhesions, may be regulated by local GSK3beta inactivation.
An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors. (1993)

Interleukin 4 (IL-4) and IL-13 share many biological functions. Both cytokines promote growth of activated human B cells and induce naive human surface immunoglobulin D+ (sIgD+) B cells to produce IgG4 and IgE. Here we show that a mutant form of human IL-4, in which the tyrosine residue at position 124 is replaced by aspartic acid (hIL-4.Y124D), specifically blocks IL-4 and IL-13-induced proliferation of B cells costimulated by anti-CD40 mAbs in a dose-dependent fashion. A mouse mutant IL-4 protein (mIL-4.Y119D), which antagonizes the biological activity of mouse IL-4, was ineffective. In addition, hIL-4.Y124D, at concentrations of up to 40 nM, did not affect IL-2-induced B cell proliferation. hIL-4.Y124D did not have detectable agonistic activity in these B cell proliferation assays. Interestingly, hIL-4.Y124D also strongly inhibited both IL-4 or IL-13-induced IgG4 and IgE synthesis in cultures of peripheral blood mononuclear cells, or highly purified sIgD+ B cells cultured in the presence of anti-CD40 mAbs. IL-4 and IL-13-induced IgE responses were inhibited > 95% at a approximately 50- or approximately 20-fold excess of hIL-4.Y124D, respectively, despite the fact that the IL-4 mutant protein had a weak agonistic activity. This agonistic activity was 1.6 +/- 1.9% (n = 4) of the maximal IgE responses induced by saturating concentrations of IL-4. Taken together, these data indicate that there are commonalities between the IL-4 and IL-13 receptor. In addition, since hIL-4.Y124D inhibited both IL-4 and IL-13-induced IgE synthesis, it is likely that antagonistic mutant IL-4 proteins may have potential clinical use in the treatment of IgE-mediated allergic diseases.