gebhart/patrepeval huggingface dataset:
Effect of dioxins on regulation of tyrosine hydroxylase gene expression by aryl hydrocarbon receptor: a neurotoxicology study (2009)

Our results suggest TCDD directly regulate the dopamine system by TH gene transactivation via an AhR-AHRE-III-mediated pathway. The AhR- mediated pathway could have a particular AhR-mediated genomic control pathway transmitting the effects of TCDD action to target cells in the development of dopaminergic disabilities.
Combination OX40 agonism/CTLA-4 blockade with HER2 vaccination reverses T-cell anergy and promotes survival in tumor-bearing mice (2016)

Immunotherapy is gathering momentum as a primary therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further. Here, we demonstrate that dual aOX40 (anti-CD134)/aCTLA-4 (anti-cytotoxic T-lymphocyte-associated protein 4) immunotherapy generated a potent antigen-specific CD8 T-cell response, enhancing expansion, effector function, and memory T-cell persistence. Importantly, OX40 and CTLA-4 expression on CD8 T cells was critical for promoting their maximal expansion following combination therapy. Animals treated with combination therapy and vaccination using anti-DEC-205 (dendritic and epithelial cells, 205 kDa)-HER2 (human epidermal growth factor receptor 2) had significantly improved survival in a mammary carcinoma model. Vaccination with combination therapy uniquely restricted Th2-cytokine production by CD4 cells, relative to combination therapy alone, and enhanced IFNγ production by CD8 and CD4 cells. We observed an increase in MIP-1α (macrophage inflammatory protein-1α)/CCL3 [chemokine (C-C motif) ligand 3], MIP-1β/CCL4, RANTES (regulated on activation, normal T-cell expressed and excreted)/CCL5, and GM-CSF production by CD8 and CD4 T cells following treatment. Furthermore, this therapy was associated with extensive tumor destruction and T-cell infiltration into the tumor. Notably, in a spontaneous model of prostate adenocarcinoma, vaccination with combination therapy reversed anergy and enhanced the expansion and function of CD8 T cells recognizing a tumor-associated antigen. Collectively, these data demonstrate that the addition of a vaccine with combined aOX40/aCTLA-4 immunotherapy augmented antitumor CD8 T-cell function while limiting Th2 polarization in CD4 cells and improved overall survival.
2.4GHz 7mW all-digital PVT-variation tolerant True Random Number Generator in 45nm CMOS (2010)

An all-digital True Random Number Generator is fabricated in 45nm CMOS with 2.4Gbps random bit throughput and total power consumption of 7mW. Two-step coarse/fine-grained tuning with a self-calibrating feedback loop enables robust operation in the presence of 20% process variation while providing immunity to run-time voltage and temperature fluctuations. The 100% digital design enables a compact layout occupying 4004μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> with measured entropy of 0.999965, and scalable operation down to 280mV, while passing all NIST RNG tests.
Fowler-Nordheim Tunneling into Thermally Grown SiO2 (1969)

Electronic conduction in thermally grown SiO2 has been shown to be limited by Fowler-Nordheim emission, i.e., tunneling of electrons from the vicinity of the electrode Fermi level through the forbidden energy gap into the conduction band of the oxide. Fowler-Nordheim characteristics have been observed over more than five decades of current for emission from Si, Al, and Mg. If previously measured values of the barrier heights are used, the slopes of the Fowler-Nordheim characteristics (log J/E2 vs 1/E) imply values of the relative effective mass in the forbidden band of about 0.4. These values take into account corrections for image-force barrier lowering and for temperature effects. The absolute values of the currents are lower by a factor of five to ten than the theoretically expected values, probably due to trapping effects. The temperature dependence of the current was found to follow the theoretical curve from 80°–420°K. However, an inconsistent relative effective mass of about 0.95 had to be assumed. These results are believed to provide the most complete examination of the Fowler-Nordheim-emission theory.
Temporal and pharmacological division of fibroblast cyclooxygenase expression into transcriptional and translational phases. (1989)

We have recently shown that the synthesis of cyclooxygenase [also called prostaglandin (PG) synthase or PG endoperoxide synthase; 8,11,14-icosatrienoate, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.1] in human dermal fibroblasts is markedly stimulated by the cytokine interleukin 1 (IL-1). We now show that the temporal sequence of the induced synthesis of PG synthase can be separated into an early transcriptional (i.e., actinomycin D inhibitable) phase and a subsequent translational (cycloheximide but not actinomycin D inhibitable) phase and that IL-1 exerts its effect during the transcriptional phase. Phorbol 12-myristate 13-acetate also stimulates synthesis of PG synthase and, together with IL-1, produces a synergistic stimulatory effect. Inhibitors of protein kinase C activation abolished the stimulatory effect of IL-1, suggesting that protein kinase C activation is a critical event in the signal-transduction sequence of the IL-1-induced increase of PG synthase synthesis. The antiinflammatory glucocorticosteroids dexamethasone and triamcinolone, but not progesterone or testosterone, were potent inhibitors of PG synthase synthesis (complete inhibition at 20 nM; IC50, 1 nM) when added during the translational phase of the synthesis sequence. The glucocorticosteroid effect was blocked by RNA and protein synthesis inhibitors. This report suggests that glucocorticosteroids exert their effect via a newly synthesized protein, causing a profound translational control of PG synthase synthesis. This novel mechanism of suppression of arachidonate metabolism is distinct from any influence of steroids on phospholipase A2 activity.
Genetic Characterization of Type 2 Porcine Circovirus (PCV-2) from Pigs with Postweaning Multisystemic Wasting Syndrome in Different Geographic Regions of North America and Development of a Differential PCR-Restriction Fragment Length Polymorphism Assay To Detect and Differentiate between Infections with PCV-1 and PCV-2 (2000)

Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Increasing evidence indicates that a variant strain of porcine circovirus (PCV), designated type 2 PCV (PCV-2), is responsible for PMWS. To determine the extent of genetic heterogeneity of PCV-2 isolates, the complete genomes of six PCV-2 isolates from different regions of North America were amplified by PCR and sequenced. Sequence and phylogenetic analyses confirmed that two distinct genotypes of PCV exist: nonpathogenic genotype PCV-1 and PMWS-associated genotype PCV-2. However, within the PCV-2 genotype, several minor branches that have been identified appear to be associated with geographic origins. The genomic sequences of two French PCV-2 isolates diverge the most from those of other PCV-2 isolates and form a distinct branch. Other minor but distinguishable branches have also been identified for a Taiwan PCV-2 isolate and two of the Canadian PCV-2 isolates. All the U.S. PCV-2 isolates are closely related, but the Canadian isolates vary, to some extent, in their genomic sequences. The data from this study indicate that although the genome of PCV-2 is generally stable among different isolates, PCV-2 isolates from different geographic regions vary in their genomic sequences. This variation may have important implications for PCV-2 diagnosis and research. On the basis of genetic analyses of available PCV strains, a universal PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed to detect and differentiate between infections with PCV-1 and PCV-2. This PCR-RFLP assay should be useful for studying the pathogenesis of PCV-2, for detecting PCV-2 infection in pigs from different geographic regions, and for screening donor pigs for use in xenotransplantation.
Effect of NiSb on the thermoelectric properties of skutterudite CoSb3 (2003)

The phase equilibrium and thermoelectric properties of Co1−xNixSb3 ternary system were examined up to high nickel content x=0.40. NiSb compound with nickel arsenide structure was observed as the impurity phase in the samples with x&amp;gt;0.10 by x-ray diffraction. The sign of the Seebeck coefficient of Co1−xNixSb3 is negative, and the absolute value of the Seebeck coefficient and electrical resistivity generally decreases with increasing x. The thermal conductivity is reduced in the samples with x⩽0.06, but above x=0.06 it increases with increasing x. These behaviors of the thermoelectric properties in the samples with low nickel content are ascribed to the substituted Ni, while those in the samples with high nickel content are ascribed to the precipitated NiSb compound. In order to more reduce the thermal conductivity of the material, we have prepared a sintered CoSb3–NiSb composite where the NiSb particles are dispersed in the CoSb3 matrix by mechanical grinding and hot pressing. The thermal conductivity of the composite is lower than that of the Co1−xNixSb3 system especially at low temperature. The decrease of the thermal conductivity is ascribed to the enhancement of the phonon scattering caused by the dispersion of NiSb particles in the CoSb3 matrix.
Chicken immunoglobulins for prophylaxis: Effect of inhaled antibodies on inflammatory parameters in rat airways (2014)

The prophylaxis against microbial airway infections of cystic fibrosis (CF) patients is an emerging application of chicken yolk antibody (IgY), however, no data on the effect of inhaled IgY have been published yet. Rats were daily (for 28 days) exposed to an aerosol of IgY, ovalbumin (OVA), Fab fragment of IgY, or PBS and their serum, bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation signs. There were no marked changes in lung parenchyma, except for an elevated number of alveolar macrophages in the OVA-exposed group. While the administration of OVA or IgY aerosols slightly increased levels of cytokine TNF-&alpha; and GRO/KC in BAL fluid, a marked elevation of GM-CSF in serum was observed after the OVA inhalation. The administration of Fab induced expression of IL-1&beta; &gt; IL-18 in serum, in contrast no effect exerted by IgY. Our results suggest that the aerosolized IgY did not cause any deleterious effects in rat lungs.
Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor (1994)

Cytokine-mobilized peripheral blood cells have been shown to participate in hematopoietic recovery after bone marrow (BM) transplantation, and are proposed to be useful targets for retrovirus- mediated gene transfer protocols. We treated mice with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) to mobilize hematopoietic progenitor cells into the peripheral blood. These cells were analyzed for the number and frequency of pluripotent hematopoietic stem cells (PHSC). We found that splenectomized animals treated for 5 days with G-CSF and SCF showed a threefold increase in the absolute number of PHSC over normal mice. The number of peripheral- blood PHSC increased 250-fold from 29 per untreated mouse to 7,200 in peripheral-blood PHSC in splenectomized animals treated for 5 days with G-CSF and SCF. Peripheral blood PHSC mobilized by treatment with G-CSF and SCF were analyzed for their ability to be transduced by retroviral vectors. Peripheral-blood PHSC from splenectomized animals G-CSF and SCF were transduced with a recombinant retrovirus containing the human MDR-1 gene. The frequency of gene transfer into peripheral blood PHSC from animals treated for 5 and 7 days was two-fold and threefold higher than gene transfer into PHSC from the BM of 5-fluorouracil-treated mice (P &lt; .01). We conclude that peripheral blood stem cells mobilized by treatment with G-CSF and SCF are excellent targets for retrovirus- mediated gene transfer.
Vaccinia Virus Subverts a Mitochondrial Antiviral Signaling Protein-Dependent Innate Immune Response in Keratinocytes through Its Double-Stranded RNA Binding Protein, E3 (2008)

Skin keratinocytes provide a first line of defense against invading microorganisms in two ways: (i) by acting as a physical barrier to pathogen entry and (ii) by initiating a vigorous innate immune response upon sensing danger signals. How keratinocytes detect virus infections and generate antiviral immune responses is not well understood. Orthopoxviruses are dermatotropic DNA viruses that cause lethal disease in humans. Virulence in animal models depends on the virus-encoded bifunctional Z-DNA/double-stranded RNA (dsRNA)-binding protein E3. Here, we report that infection of mouse primary keratinocytes with a vaccinia DeltaE3L mutant virus triggers the production of beta interferon (IFN-beta), interleukin-6 (IL-6), CCL4, and CCL5. None of these immune mediators is produced by keratinocytes infected with wild-type vaccinia virus. The dsRNA-binding domain of E3 suffices to prevent activation of the innate immune response. DeltaE3L induction of IFN-beta, IL-6, CCL4, and CCL5 secretion requires mitochondrial antiviral signaling protein (MAVS; an adaptor for the cytoplasmic viral RNA sensors RIG-I and MDA5) and the transcription factor IRF3. IRF3 phosphorylation is induced in keratinocytes infected with DeltaE3L, an event that depends on MAVS. The response of keratinocytes to DeltaE3L is unaffected by genetic ablation of Toll-like receptor 3 (TLR3), TRIF, TLR9, and MyD88.
CREB3L2-PPARγ Fusion Mutation Identifies a Thyroid Signaling Pathway Regulated by Intramembrane Proteolysis (2008)

The discovery of gene fusion mutations, particularly in leukemia, has consistently identified new cancer pathways and led to molecular diagnostic assays and molecular-targeted chemotherapies for cancer patients. Here, we report our discovery of a novel CREB3L2-PPARgamma fusion mutation in thyroid carcinoma with t(3;7)(p25;q34), showing that a family of somatic PPARgamma fusion mutations exist in thyroid cancer. The CREB3L2-PPARgamma fusion encodes a CREB3L2-PPARgamma fusion protein that is composed of the transactivation domain of CREB3L2 and all functional domains of PPARgamma1. CREB3L2-PPARgamma was detected in <3% of thyroid follicular carcinomas. Engineered overexpression of CREB3L2-PPARgamma induced proliferation by 40% to 45% in primary human thyroid cells, consistent with a dominant oncogenic mechanism. Wild-type CREB3L2 was expressed in the thyroid as a bZIP transcription factor with a transmembrane domain that has flanking S1P and S2P proteolytic cleavage sites. Native CREB3L2 was cleaved to nuclear CREB3L2 by regulated intramembrane proteolysis in normal thyroid cells that expressed the S1P and S2P proteases. Nuclear CREB3L2 stimulated transcription 8-fold from the EVX1 cyclic AMP (cAMP) response element in the absence of cAMP, whereas CREB3L2-PPARgamma inhibited transcription 6-fold from EVX1 in the same experiments. CREB3L2-PPARgamma also inhibited 4-fold the expression of thyroglobulin, a native cAMP-responsive gene, in primary thyroid cells treated with thyroid-stimulating hormone. Our findings identify a novel CREB3L2-PPARgamma gene fusion mutation in thyroid carcinoma and reveal a thyroid signaling pathway that is regulated by intramembrane proteolysis and disrupted in cancer.
Molecular and cellular mechanisms of muscle aging and sarcopenia and effects of electrical stimulation in seniors (2015)

The prolongation of skeletal muscle strength in aging and neuromuscular disease has been the objective of numerous studies employing a variety of approaches. It is generally accepted that cumulative failure to repair damage related to an overall decrease in anabolic processes is a primary cause of functional impairment in muscle. The functional performance of skeletal muscle tissues declines during post- natal life and it is compromised in different diseases, due to an alteration in muscle fiber composition and an overall decrease in muscle integrity as fibrotic invasions replace functional contractile tissue. Characteristics of skeletal muscle aging and diseases include a conspicuous reduction in myofiber plasticity (due to the progressive loss of muscle mass and in particular of the most powerful fast fibers), alteration in muscle-specific transcriptional mechanisms, and muscle atrophy. An early decrease in protein synthetic rates is followed by a later increase in protein degradation, to affect biochemical, physiological, and morphological parameters of muscle fibers during the aging process. Alterations in regenerative pathways also compromise the functionality of muscle tissues. In this review we will give an overview of the work on molecular and cellular mechanisms of aging and sarcopenia and the effects of electrical stimulation in seniors..
Quantitation of extrahepatic metabolism. Pulmonary and intestinal conjugation of naphthol. (1986)

There is much evidence in the literature to indicate extrahepatic conjugation of naphthol by various isolated tissue preparations. Using in vivo methodology, where multiple sites of input are employed, it has been demonstrated that both lung and intestinal mucosa make a significant contribution in the conjugation of naphthol in the rat. Under the conditions studied, both of the above organs (pulmonary extraction ratio 0.44, intestinal extraction ratio 0.46) are more than twice as effective as the liver in eliminating naphthol (hepatic extraction ratio 0.18). This multiple sites of input method has been compared with a multiple sites of sampling method. Similar results have been obtained in quantifying pulmonary conjugation of naphthol. The relevant merits of the two approaches are discussed.
An Improved Synthesis of Pyran-3,5-dione:  Application to the Synthesis of ABT-598, a Potassium Channel Opener, via Hantzsch Reaction (2006)

Ketoester 1 is cyclized to give pyran-3,5-dione 2 in 78% yield using a parallel addition of ketoester 1 and base NaO(t)Bu in refluxing THF. Compared to the previously reported procedures, these optimized conditions have significantly increased the yield of this transformation and the quality of pyran 2 and prove to be suitable for large-scale preparation. An application of 2 to the synthesis of ABT-598, a potassium channel opener, is demonstrated.
Packet Radio in the Amateur Service (1985)

During the past several years there has been much activity in the development of networking hardware and software for personal computers. At the same time the amateur radio community has been equally active in the development of networking equipment and procedures especially suited for radio circuits. Although the initial efforts have been with terrestrial circuits, experimentation with and development of satellite-based systems is well underway. While we are aware of the many commercial and government organizations active in specialized packet radio systems, our goal is to establish radio networks with inexpensive equipment that is within reach of a large number of individuals with limited budgets. This article will provide a brief history of hardware, software, and protocol development activities as well as a description of amateur packet radio operations. Also discussed are satellite-based operations and development efforts. These include AMSAT-OSCAR-10 and UoSAT-OSCAR-11, currently operating in orbit, and PACSAT, JAS-1, and Phase 3-C, in the design and construction phases.
Targeting the neurotoxic species in Alzheimer's disease: inhibitors of Aβ oligomerization (2004)

In the past two decades, a large body of evidence has established a causative role for the beta-amyloid peptide (Abeta) in Alzheimer's disease (AD). However, recent debate has focused on whether amyloid fibrils or soluble oligomers of Abeta are the main neurotoxic species that contribute to neurodegeneration and dementia. Considerable early evidence has indicated that amyloid fibrils are toxic, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins. While this crucial aspect of AD pathogenesis remains controversial, effective therapeutic strategies should ideally target both oligomeric and fibrillar species of Abeta. Here, we describe the anti-amyloidogenic and neuroprotective actions of some di- and tri-substituted aromatic compounds. Inhibition of the formation of soluble Abeta oligomers was monitored using a specific antibody-based assay that discriminates between Abeta oligomers and monomers. Thioflavin T and electron microscopy were used to screen for inhibitors of fibril formation. Taken together, these results led to the identification of compounds that more effectively block Abeta oligomerization than fibrillization. It is significant that such compounds completely blocked the neurotoxicity of Abeta to rat hippocampal neurons in culture. These findings provide a basis for the development of novel small molecule Abeta inhibitors with potential applications in AD.
Uchi Maius et Carthage, I : C(aius) Marius C(ai) F(ilius) Arn(ensi tribu) Extricatus (2004)

The archaeological exploration of Uchi Maius enlightens epigraphic documentation, the old one as well as the new one. Now we can reconsider relations between this pagus and Carthage through the destiny of some personnages or families. The inscription of C(aius) Marius Extricatus might give indications on two levels of exercising responsabilities : the local level within the pagus, and the colonial level at Carthage. So we must sound not only the silences of documentation, which rather likes to show the most distinguishable elements of people life, but also initiate the criticism of the « droit latin subordonné » notion, because it doesn 't seem to allow a good explaination of the rare documents which show entrance of new members in the ordo of the colony of Carthage.
Modulation of inositol 1,4,5‐triphosphate concentration by prolyl endopeptidase inhibition (2002)

Prolyl endopeptidase (PEP) is a proline-specific oligopeptidase with a reported effect on learning and memory in different rat model systems. Using the astroglioma cell line U343, PEP expression was reduced by an antisense technique. Measuring different second-messenger concentrations revealed an inverse correlation between inositol 1,4,5-triphosphate [Ins(1,4,5)P3] concentration and PEP expression in the generated antisense cell lines. However, no effect on cAMP generation was observed. In addition, complete suppression of PEP activity by the specific inhibitor, Fmoc-Ala-Pyrr-CN (5 micro m) induced in U343 and other cell lines an enhanced, but delayed, increase in Ins(1,4,5)P3 concentration. This indicates that the proteolytic activity of PEP is responsible for the observed effect. Furthermore, the reduced PEP activity was found to amplify Substance P-mediated stimulation of Ins(1,4,5)P3. The effect of reduced PEP activity on second-messenger concentration indicates a novel intracellular function of this peptidase, which may have an impact on the reported cognitive enhancements due to PEP inhibition.