gebhart/patrepeval huggingface dataset:
Effect of N-acetylcysteine on the pulmonary response to endotoxin in the awake sheep and upon in vitro granulocyte function. (1984)

Oxygen free radicals released during endotoxemia may contribute to the lung injury of the adult respiratory distress syndrome (ARDS). As this syndrome occurs frequently after gram-negative sepsis in humans, we studied the effect of intravenous N-acetylcysteine (NAC), a free radical scavenger, upon the endotoxin (E)-induced model of ARDS in awake sheep. In vivo studies demonstrated that NAC attenuates the endotoxin-induced rise in pulmonary artery pressure (62 +/- 3 torr with E control vs. 43 +/- 3 torr for E + NAC), and markedly diminishes the rise in lymph flow at 1 h (8.5 +/- 1.2 vs 4.5 +/- 0.6 ml/15 min) and 4 h (5.0 +/- 0.6 vs. 3.3 +/- 0.4 ml/15 min), respectively, for E control vs. E + NAC. NAC also markedly attenuated the alterations in lung mechanics after endotoxemia. Dynamic compliance at 2 h after endotoxemia was 44 +/- 6% of base line for E vs. 76 +/- 10% of base line for E + NAC. Resistance to airflow across the lung at 1 h postendotoxin was 811 +/- 280% of base line for E vs. 391 +/- 233% of base line for E + NAC. NAC substantially reduced the 1 h postendotoxin rise in lymph concentrations of thromboxane B2 (8.29 +/- 3.28 vs. 2.75 +/- 1.93 ng/ml for E vs. E + NAC) and 6-keto-prostaglandin-F1 alpha (0.91 +/- 0.27 vs. 0.23 +/- 0.12 ng/ml for E vs. E + NAC). In addition, in vitro studies were performed which revealed NAC to be a potent free radical scavenger in both biologic and nonbiologic free radical generating systems. NAC decreased phorbol-stimulated granulocyte aggregation in a concentration-dependent manner in vitro. Minimal effects were observed, however, upon leukocyte degranulation at the concentrations of NAC achieved during the in vivo tests. Thus, NAC significantly attenuated all monitored pathophysiologic changes in the endotoxin model of ARDS in sheep, possibly by its ability to scavenge toxic oxygen free radicals. A direct impairment of the ability of inflammatory cells to generate oxygen radicals cannot be ruled out.
Internal surface area and other measurements in emphysema (1967)

Some measurements of emphysema were made on 29 pairs of non-emphysematous lungs and 44 pairs of emphysematous lungs inflated at a standard transpulmonary pressure of 25 cm. of formalin. These were: a subjective visual assessment (units); an assessment of the volume of the lung parenchyma involved by emphysema (point count); an average subjective visual grading by eight pathologists (Co-op score); mean linear intercept or average distance between alveolar walls at a transpulmonary pressure of 25 cm. of formalin (Lm); mean linear intercept corrected to total lung capacity (Lm<sub>C</sub>); internal (alveolar) surface area at 25 cm. transpulmonary pressure (ISA); internal surface area at total lung capacity (ISA<sub>C</sub>); internal surface area corrected to an arbitrary lung volume of 5 litres (ISA<sub>5</sub>). Internal surface area measurements were generally decreased in severe emphysema. Because of the wide range of ISA and ISA<sub>C</sub> in non-emphysematous lungs, most emphysematous lungs fell within the normal range. The range of ISA<sub>5</sub> was smaller in non-emphysematous lungs and most emphysematous lungs fell outside this range. ISA<sub>5</sub> in `mild9 emphysema was not distinguishable from non-emphysematous lungs. Most emphysematous lungs in which the surface area was decreased less than expected from subjective assessment were examples of centrilobular emphysema. Lm and Lm<sub>C</sub> were increased in emphysema. ISA<sub>5</sub>, Lm, and Lm<sub>C</sub> paralleled the subjective assessments of emphysema rather better than ISA or ISA<sub>C</sub>, even when the latter were expressed as a percentage of predicted. Lm and Lm<sub>C</sub> in lungs with mild emphysema fell within the ranges found in non-emphysematous lungs, but the mean value of Lm in lungs with `mild9 emphysema was different from the mean Lm of non-emphysematous lungs, at conventional levels of significance. Since objective methods did not recognize adequately examples of `mild9 emphysema, a subjective visual grading system (with its limitations) may have a definite place.
Bombesin-like peptides: studies on food intake and social behaviour with receptor knock-out mice (2000)

Bombesin (BN)-like peptides and receptors for these peptides are widely distributed in mammalian peripheral tissues and the central nervous system. The physiological and behavioural functions of these peptides have been clarified by both in vivo and in vitro studies. In spite of intensive investigations, the functions of endogenous BN-like peptides remain unclear. In order to specify these functions, our group and another laboratory generated by gene targeting mutant mice that lack one of the three BN-like peptide receptors found in mammals, ie neuromedin B receptor (NMB-R; BB1), gastrin-releasing peptide receptor (GRP-R; BB2), or bombesin receptor subtype-3 (BRS-3; BB3). Using these mutant mouse, we have found unexpected phenotypes, such as hyperphagia and obesity in the BRS-3-deficient mouse, and abnormal social behaviour in the GRP-R-deficient mouse. In the present study, we present our most recent findings in addition to previous studies and discuss the functions of BN-like peptides related to feeding and social behaviour from the point of view of knock-out mice studies.
System Modeling for V&V (1992)

Abstract Simulation and formal models are becoming an accepted part of the early stages of system design. This paper discusses the use of executable system models during system design and implementation. RTI recently developed an abstract executable model of the operating system developed for an avionics test bed based on the PAVE PILLAR architecture. The target hardware consisted of two processing clusters, each with five VHSIC 1750A modules connected by a parallel bus and a system mass memory. The three components are connected by two optical high‐speed data busses. The modeling was done while both the hardware and software were under development. The process of developing and validating the models produced a significant V&amp;V payoff for the design teams. Formal modeling forced early consideration of hardware/software, inter‐module, and inter‐application interfaces that were overlooked during the system design process. This led to forecasting system problems that normally would not have been discovered until system integration. This paper will review the modeling effort and show, in a systems engineering context, how abstract modeling can serve as a powerful method for early discovery of interface errors normally not found until integration.
Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle (2010)

Muscle contraction relies on a highly organized intracellular network of membrane organelles and cytoskeleton proteins. Among the latter are the intermediate filaments (IFs), a large family of proteins mutated in more than 30 human diseases. For example, mutations in the DES gene, which encodes the IF desmin, lead to desmin-related myopathy and cardiomyopathy. Here, we demonstrate that myotubularin (MTM1), which is mutated in individuals with X-linked centronuclear myopathy (XLCNM; also known as myotubular myopathy), is a desmin-binding protein and provide evidence for direct regulation of desmin by MTM1 in vitro and in vivo. XLCNM-causing mutations in MTM1 disrupted the MTM1-desmin complex, resulting in abnormal IF assembly and architecture in muscle cells and both mouse and human skeletal muscles. Adeno-associated virus-mediated ectopic expression of WT MTM1 in Mtm1-KO muscle reestablished normal desmin expression and localization. In addition, decreased MTM1 expression and XLCNM-causing mutations induced abnormal mitochondrial positioning, shape, dynamics, and function. We therefore conclude that MTM1 is a major regulator of both the desmin cytoskeleton and mitochondria homeostasis, specifically in skeletal muscle. Defects in IF stabilization and mitochondrial dynamics appear as common physiopathological features of centronuclear myopathies and desmin-related myopathies.
N-Methyl-D-aspartate receptors are clustered and immobilized on dendrites of living cortical neurons. (1993)

The response of nerve cells to synaptic inputs and the propagation of this activation is critically dependent on the cell-surface distribution of ion channels. In the hippocampus, Ca2+ influx through N-methyl-D-aspartate receptors (NMDAR) and/or voltage-dependent calcium channels on dendrites is thought to be critically involved in long-term potentiation, neurite outgrowth, epileptogenesis, synaptogenesis, and cell death. We report that conantokin-G (CntxG), a peptide from Conus geographus venom, competitively blocked with high affinity and specificity NMDAR-mediated currents in hippocampal neurons and is a reliable probe for exploring NMDAR distribution. Fluorescent derivatives of CntxG were prepared and used to directly determine NMDAR distribution on living hippocampal neurons by digital imaging and confocal fluorescence microscopy. In hippocampal slices, the CA1 dendritic subfield was strongly labeled by CntxG, whereas the CA3 mossy fiber region was not. On CA1 hippocampal neurons in culture, dendritic CntkG-sensitive NMDAR were clustered at sites of synaptic contacts, whereas somatic NMDAR were distributed diffusely and in patches. NMDAR distribution differed from the distribution of voltage-dependent calcium channels. A significant fraction of labeled NMDAR on somata and dendrites was found to be highly mobile: rates were consistent with the possible rapid recruitment of NMDAR to specific synaptic locations. The localization of NMDAR and modulation of this distribution demonstrated here may have important implications for the events that underlie neuronal processing and synaptic remodeling during associative synaptic modification.
An Open-label Pilot Trial of Ibandronate for Complex Regional Pain Syndrome (2008)

These data justify a randomized, double-blind, placebo-controlled trial of ibandronate that should perhaps be limited to patients with hand CRPS.
Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics (2013)

Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.
Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis (2007)

The focus of the present study was whether and how infiltrating macrophages play a role in angiogenesis and the growth of cancer cells in response to the inflammatory cytokine interleukin (IL)-1beta. Lewis lung carcinoma cells overexpressing IL-1beta grew faster and induced greater neovascularization than a low IL-1beta-expressing counterpart in vivo. When macrophages were depleted using clodronate liposomes, both neovascularization and tumor growth were reduced in the IL-1beta-expressing tumors. Co-cultivation of IL-1beta-expressing cancer cells with macrophages synergistically augmented neovascularization and the migration of vascular endothelial cells. In these co-cultures, production of the angiogenic factors vascular endothelial growth factor-A and IL-8, monocyte chemoattractant protein-1, and matrix metalloproteinase-9 were increased markedly. The production of these factors, induced by IL-1beta-stimulated lung cancer cells, was blocked by a nuclear factor (NF)-kappaB inhibitor, and also by the knockdown of p65 (NF-kappaB) and c-Jun using small interference RNA, suggesting involvement of the transcription factors NF-kappaB and AP-1. These results demonstrated that macrophages recruited into tumors by monocyte chemoattractant protein-1 and other chemokines could play a critical role in promoting tumor growth and angiogenesis, through interactions with cancer cells mediated by inflammatory stimuli.
Chiral Pool Synthesis of 8-Hydroxymethyl-"9-oxa"-anthracyclinones (1987)

The synthesis of title compounds from (R)-2,3-0-isoprapylidene glyceraldehyde and leucoquinirarin is reported.Doxorubicin (1) and daunorubicin.(L)are glycoside antibiotics widely used in the 1 chemotherapic treatment of different human cancers . 1 R = W -3 R = H -5 R-H or sugar -2 R -H -4 R = (N-dimethylacosamine) -On the other hand, different pyranonaphthoqulnone antibiotics including kalafungin (3) or its enantiomer nanaomycin D and closely related nanaomycin A have been 2 shown to possess significant antimicrobialogical properties .It has also been postulated that these compounds would possess some antineoplastic activities as 3 bioreductive alkylating agents .This has been supported by the recent discovery of lactoquinomycin (q)4, an amino-glycoside of kalafungin which displayed antitumor activity although its mechanism of action has not yet been reported.Synthesis of new analogs of 1 and 2 with an oxygen in the A ring instead of both the side-chain and axial OH at C-Q and with a hydroxymethyl side-chain at C-8 such as the 5,12-dihydroxy-3-hydr0~ymethyl-3,4-dihydro-lH-anthra[2,3-c]pyran-6,1~- d i m e ( R = H), has been undertaken.Intercalation with native DNA must be less marked with these new glyco~ides of general formula i than with 1 and 1 since it
Syntactic structure analysis in uveal melanomas. (1994)

Syntactic structure analysis was carried out successfully on 92 paraffin embedded uveal melanomas, taken from patients with a minimum follow up of 5 years. This simple, fast, and reproducible method of describing the tumour architecture has been significantly correlated with malignancy in tumours from several sites. Paraffin sections 5 microns thick, were cut and stained with haematoxylin and eosin. Tumours were classified according to a modification of the Callender classification. A minimum spanning tree (MST), using the centre points of tumour nuclei, was constructed in five randomly chosen fields with an interactive digitising video overlay system. Ten syntactic structure features were derived from each MST; subsequently, the mean and standard deviation of the five fields analysed were calculated for further statistical analysis. Reproducibility was acceptable with a mean correlation coefficient of 0.70. In univariate survival analysis, the percentage of points with three neighbours yielded prognostic significance (p < 0.05). Minimum spanning tree variables were compared (chi 2 test) with classic tumour prognosticators and there was a significant correlation between Callender cell type and the following MST parameters: mean number of points (p < 0.003); MST length (p < 0.003); mean line length (p < 0.01); number of nuclei with one neighbour (p < 0.004); number of nuclei with two neighbours (p < 0.02), and number of nuclei with three neighbours (p < 0.005). Syntactic structure analysis is an evolving technique, but may be able to mathematically (and reproducibly) describe melanoma architecture across the spectrum of the Callender classes. This would also allow architectural grading of tumours within the specific Callender groups, providing more precise prognostic information. Further modifications of this technique are necessary to optimise prognostic potential when applied to uveal melanomas.
Over-40-GHz modulation bandwidth of EAM-integrated DFB laser modules (2002)

Electroabsorption modulator (EAM)-DFB modules with record high bandwidth of 41 GHz have been developed. 40 Gb/s NRZ operation with 12 dB extinction ratio and 40 GHz short pulse trains with 6 ps pulse width have been successfully achieved.
Rate Enhancement by Ethylene in the Ru‐Catalyzed Ring‐Closing Metathesis of Enynes: Evidence for an “Ene‐then‐Yne” Pathway that Diverts through a Second Catalytic Cycle (2005)

Mixing it: A dual-substrate/dual isotopic labeling strategy has shown that the accelerating effect of ethylene in intermolecular ring-closing metathesis of enynes is best explained by an ene-then-yne mechanism rather than the commonly proposed yne-then-ene mechanism (see picture).
Overcoming the customization bottleneck using example-based MT (2001)

We describe MSR-MT, a large-scale hybrid machine translation system under development for several language pairs. This system's ability to acquire its primary translation knowledge automatically by parsing a bilingual corpus of hundreds of thousands of sentence pairs and aligning resulting logical forms demonstrates true promise for overcoming the so-called MT customization bottleneck. Trained on English and Spanish technical prose, a blind evaluation shows that MSR-MT's integration of rule-based parsers, example based processing, and statistical techniques produces translations whose quality exceeds that of uncustomized commercial MT systems in this domain.
Analysis for TNF-α Using Solid-Phase Affinity Capture with Radiolabel and MALDI-MS Detection (1999)

Screening of mutant mice for subtle phenotypes requires sensitive, high-throughput analyses of sentinel proteins in functional pathways. The cytokine TNF-alpha is upregulated during inflammatory reactions associated with autoimmune diseases. We have developed a method to monitor the concentration of TNF-alpha under physiological conditions. TNF-alpha is captured, purified, and concentrated using monoclonal antibody-coated microbeads. The capture is efficient (> 80%) and can be used in the concentration range < 100 pg/mL to > 50 ng/mL, as determined by detection of 125I-labeled TNF-alpha. The bead capture of TNF-alpha can be combined with direct detection by MALDI-MS for sample concentrations of > 10 ng/mL. TNF-alpha can be captured and detected from diluted mouse serum, with minimal interferences observed in the MALDI spectrum. This method is adaptable to high-throughput sample handling with microfluidic devices and automated mass spectrometric analysis.
Expression of PAX8-PPARγ1 Rearrangements in Both Follicular Thyroid Carcinomas and Adenomas (2002)

Recently, a translocation t(2;3)(q13;p25), leading to the formation of a chimeric PAX8-peroxisome proliferator-activated receptor (PPAR)gamma 1 oncogene, was detected in follicular thyroid carcinomas (FTC), but not in follicular thyroid adenomas (FTA), papillary thyroid carcinomas (PTC), or multinodular hyperplasias. However, previous cytogenetic studies have identified the t(2;3)(q13;p25) translocation also in some cases of FTA. In this study, we have combined RT-PCR with primers in exons 4-8 of PAX8 and in exon 1 of PPAR gamma 1 with PPAR gamma immunohistochemistry to study PAX8-PPAR gamma 1 oncogene activation in FTC (n = 9), FTA (n = 16), PTC (n = 9), anaplastic thyroid carcinomas (n = 4), and multinodular hyperplasias (n = 2). PAX8-PPAR gamma 1 rearrangements were detected by RT-PCR in 5 of 9 (56%) FTC and in 2 of 16 (13%) FTA. By contrast, all cases of PTC, anaplastic thyroid carcinomas, and multinodular hyperplasia were RT-PCR-negative. Diffuse nuclear immunoreactivity for PPAR gamma was observed in 7 of 9 (78%) FTC, 5 of 16 FTA (31%), and 1 of 9 PTC (11%). Positivity was focal in 3 cases (1 FTC, 1 PTC, and 1 multinodular hyperplasia). Diffuse nuclear staining for PPAR gamma was present in RT-PCR- negative cases of FTC (n = 3), FTA (n = 3), and PTC (n = 1), suggesting that a different PAX8-PPAR gamma 1 breakpoint, a rearrangement between PPAR gamma 1 and a non-PAX8 partner, or overexpression of the native protein might be present. Our findings that PAX8-PPAR gamma 1 rearrangements are present in both follicular carcinomas and adenomas suggest that this oncogene is not a reliable marker to differentiate between FTC and FTA in fine-needle aspiration biopsies of follicular neoplasms of the thyroid.
A Potent Indole-3-Carbinol–Derived Antitumor Agent with Pleiotropic Effects on Multiple Signaling Pathways in Prostate Cancer Cells (2007)

Indole-3-carbinol has emerged as a promising chemopreventive agent due to its in vivo efficacy in various animal models. However, indole-3-carbinol exhibits weak antiproliferative potency and is unstable in acidic milieu. Thus, this study was aimed at exploiting indole-3-carbinol to develop potent antitumor agents with improved chemical stability. This effort culminated in OSU-A9 {[1-(4-chloro-3-nitrobenzenesulfonyl)-1H-indol-3-yl]-methanol}, which is resistant to acid-catalyzed condensation, and exhibits 100-fold higher apoptosis-inducing activity than the parent compound. Relative to indole-3-carbinol, OSU-A9 displays a striking qualitative similarity in its effects on the phosphorylation or expression of multiple signaling targets, including Akt, mitogen-activated protein kinases, Bcl-2 family members, survivin, nuclear factor-kappaB, cyclin D1, p21, and p27. The ability of OSU-A9 to concurrently modulate this broad range of signaling targets underscores its in vitro and in vivo efficacy in prostate cancer cells. Nevertheless, despite this complex mode of mechanism, normal prostate epithelial cells were less susceptible to the antiproliferative effect of OSU-A9 than PC-3 and LNCaP prostate cancer cells. Treatment of athymic nude mice bearing established s.c. PC-3 xenograft tumors with OSU-A9 at 10 and 25 mg/kg i.p. for 42 days resulted in a 65% and 85%, respectively, suppression of tumor growth. Western blot analysis of representative biomarkers in tumor lysates revealed significant reductions in the intratumoral levels of phosphorylated (p-) Akt, Bcl-xL, and RelA, accompanied by robust increases in p-p38 levels. In conclusion, the ability of OSU-A9 to target multiple aspects of cancer cell survival with high potency suggests its clinical value in prostate cancer therapy.
Instruction selection, resource allocation, and scheduling in the AVIV retargetable code generator (1998)

The AVIV retargetable code generator produces optimized machine code for target processors with different instruction set architectures AVIV optimizes for minimum code size.
Increased Soluble Tumor Necrosis Factor Receptor Levels in the Serum of Elderly People (2000)

Increased sTNF-R levels may oppose the physiologic and protective effects of TNF by interference with its receptor binding. This interaction may contribute to the susceptibility of the elderly to infectious and neoplastic diseases.
An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations (2006)

Aging is an inherently complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Although the fundamental mechanisms are still poorly understood, a growing body of evidence points toward reactive oxygen species (ROS) as one of the primary determinants of aging. The "oxidative stress theory" holds that a progressive and irreversible accumulation of oxidative damage caused by ROS impacts on critical aspects of the aging process and contributes to impaired physiological function, increased incidence of disease, and a reduction in life span. While compelling correlative data have been generated to support the oxidative stress theory, a direct cause-and-effect relationship between the accumulation of oxidatively mediated damage and aging has not been strongly established. The goal of this minireview is to broadly describe mechanisms of in vivo ROS generation, examine the potential impact of ROS and oxidative damage on cellular function, and evaluate how these responses change with aging in physiologically relevant situations. In addition, the mounting genetic evidence that links oxidative stress to aging is discussed, as well as the potential challenges and benefits associated with the development of anti-aging interventions and therapies.
Pyridine as trigger for chloride isomerisation in chelated ruthenium benzylidene complexes: implications for olefin metathesis (2011)

The cationic pyridine adduct of a ruthenium complex bearing a chelating benzylidene and an N-heterocyclic carbene was identified as an intermediate during the activation of cis dichloro species and a novel triggering concept for olefin metathesis catalysts based on cationic species was disclosed.