gebhart/patrepeval huggingface dataset:
Extended lifespan of Barrett's esophagus epithelium transduced with the human telomerase catalytic subunit: a useful in vitro model (2003)

As there has been no previous information on the consequences of telomerase expression in genetically altered, mortal cells derived from pre-malignant tissue, we sought to determine the effect of hTERT (human catalytic subunit of telomerase reverse transcriptase) transduction of pre-malignant cell strains from Barrett's esophagus that do not contain telomerase activity and possess a finite lifespan. Primary cultures of Barrett's esophageal epithelium transduced with a retrovirus containing hTERT were characterized by growth factor requirements, cytogenetics and flow cytometry. Expression of telomerase lengthened telomeres and greatly extended the lifespan of hTERT transduced (hTERT+) Barrett's esophagus cells. Growth factor dependency of the hTERT+ cultures remained largely similar to the parental cultures, although there was a modest increase in the ability to grow in agar. Chromosomal instability, measured by both karyotypic and FISH (fluorescence in situ hybridization) analyses, was reduced but not abrogated by hTERT transduction, suggesting that telomerase expression can enhance genomic stability. However, the persistence of residual instability gave rise to new clonal and non-clonal genetic variants, and in one hTERT+ culture a new DNA aneuploid population was observed, the only time such a ploidy shift has been seen in Barrett's cell strains in vitro. These in vitro observations are analogous to the clinical progression to aneuploidy that often precedes cancer in Barrett's esophagus, and suggest that reactivation of telomerase may be permissive for continued genetic evolution to cancer. Long-lived Barrett's esophagus epithelial cultures should provide a useful in vitro model for studies of neoplastic evolution and chemopreventive therapies.
Local Cerebral Blood Flow during Hibernation, a Model of Natural Tolerance to “Cerebral Ischemia” (1994)

The breakdown of cellular homeostasis and progressive neuronal destruction in cerebral ischemia appears to be mediated by a complex network of causes that are intricately interrelated. We have investigated a physiological state existing normally in nature in which mammals appear to tolerate the ordinarily detrimental effects of ischemia with reduced oxygen availability and to resist activation of self-destructive processes, i.e., mammalian hibernation. Ground squirrels (Spermophilus tridecemlineatus) were chronically implanted with arterial and venous catheters and telemetry devices for electroencephalography, electrocardiography, and monitoring of body temperature. The animals were placed in an environmental chamber at an ambient temperature of 5 degrees C. Entrance into hibernation was characterized by a drop in heart rate followed by a gradual decline in body temperature and an isoelectric electroencephalogram. Cold-adapted active animals that were not hibernating served as controls. Cerebral blood flow (CBF) was measured in both groups with the autoradiographic [14C]iodoantipyrine method. Mean (+/- SD) mass-weighted CBF in the brain was 62 +/- 18 ml 100 g(-1) min (-1) (n = 4) in the control group but was reduced to ischemic levels, 7 +/- 4 ml 100 g(-1) min (-1) (n = 4), in the hibernating animals (p < 0.001) [corrected]. No neuropathological changes were found in similarly hibernating animals aroused from hibernation. Hibernation appears to be actively regulated, and hormonal factors may be involved. The identification and characterization of such factors and of the mechanisms used by hibernating species to increase ischemic tolerance and to blunt the destructive effects of ischemia may enable us to prevent or minimize the loss of homeostatic control during and after cerebral ischemia in other species.
FETAL ANDROGEN EXPOSURE INHIBITS FETAL RAT LUNG FIBROBLAST LIPID UPTAKE AND RELEASE (2001)

Fetal lung fibroblasts provide lipid substrate for type II cell surfactant phospholipid synthesis. This process is developmental and glucocorticoid dependent. Previous studies in our laboratory demonstrating sex differences in several aspects of lung maturation suggest that these differences may be due to effects of fetal androgens. Based on these studies, we hypothesized that fetal lung fibroblast triglyceride metabolism is determined by opposing effects of fetal androgens and glucocorticoids. To model the effects of androgens on fetal lung fibroblast triglyceride metabolism, pregnant rats were treated with dihydrotestosterone (DHT) 1 mg/kg/day from the days 15 to 20 of gestation, and changes in triglyceride content of freshly isolated fetal rat lung fibroblasts (FRLF) and rates of uptake and prostaglandin E2(PGE2)-mediated release by cultured FRLFin response to glucocorticoids in the presence or absence of DHT in vitro were measured. During lung development, the triglyceride content and rate of uptake of female-derived FRLF increased 3.5- and 4.8-fold, respectively, between days 18 and 20 of gestation. From days 19 to 22, male FRLF trigyclyceride content and rate of uptake were lower than the content and uptake by female FRLF. Maternal DHT treatment inhibited the normal developmental increase in fibroblast triglyceride content and rate of uptake between days 19 and 22 by both male and female FRLF. In the absence of maternal DHT, in vitro dexamethasone stimulated triglyceride uptake 3-fold by day 21 in FRLF. This effect was blocked by maternal pretreatment with DHT. Maternal DHT exposure prevented stimulation of triglyceride release by PGE2. Although in vitro dexamethasone stimulated triglyceride release by maternal DHT-exposed fibroblasts, it did not enhance the response to PGE2. These data suggest that in utero exposure to androgens (1) delay the developmental increase in triglyceride content and (2) oppose the effects of glucocorticoid on cultured FRLF triglyceride uptake and PGE2-mediated release.
Defective angiogenesis and fatal embryonic hemorrhage in mice lacking core 1–derived O-glycans (2004)

The core 1 beta1-3-galactosyltransferase (T-synthase) transfers Gal from UDP-Gal to GalNAcalpha1-Ser/Thr (Tn antigen) to form the core 1 O-glycan Galbeta1-3GalNAcalpha1-Ser/Thr (T antigen). The T antigen is a precursor for extended and branched O-glycans of largely unknown function. We found that wild-type mice expressed the NeuAcalpha2-3Galbeta1-3GalNAcalpha1-Ser/Thr primarily in endothelial, hematopoietic, and epithelial cells during development. Gene-targeted mice lacking T-synthase instead expressed the nonsialylated Tn antigen in these cells and developed brain hemorrhage that was uniformly fatal by embryonic day 14. T-synthase-deficient brains formed a chaotic microvascular network with distorted capillary lumens and defective association of endothelial cells with pericytes and extracellular matrix. These data reveal an unexpected requirement for core 1-derived O-glycans during angiogenesis.
Metal‐Free Benzylic C−H Amination via Electrochemically Generated Benzylaminosulfonium Ions (2016)

Electrochemical oxidation of toluene derivatives in the presence of N-tosyldiphenylsulfilimine gave the corresponding benzylaminosulfonium ions, which were treated with tetrabutylammonium iodide under non-electrolytic conditions to give N-tosylbenzylamines. The transformation serves as a metal- and chemical-oxidant-free method for benzylic C-H amination. Because of high oxidation potential of N-tosyldiphenylsulfilimine the present method can be applied to synthesis of various benzylamines from functionalized toluene derivatives.
Insulin Resistance after Surgery: Normalization by Insulin Treatment (1990)

1. Injury is known to be associated with variable degrees of tissue insensitivity to insulin. We measured insulin resistance in a group of non-obese, glucose-tolerant patients undergoing major elective surgery with an uncomplicated post-operative course. 2. Shortly after surgery, hyperglycaemia (7.3 +/- 0.6 versus 4.2 +/- 0.3 mmol/l glucose pre-surgery, mean +/- SEM, P less than 0.01) with normal insulin concentrations (73 +/- 15 versus 64 +/- 18 pmol/l) suggested the presence of insulin resistance. Counter-regulatory hormones were raised, whole-body protein oxidation was doubled (P less than 0.01) and energy expenditure was up by 18% (P less than 0.01). 3. Insulin sensitivity was quantified by clamping plasma glucose concentrations at 5.6 mmol/l during 24 h of total parenteral nutrition (15% protein, 55% glucose and 30% fat, supplying 1.25 times the measured resting energy expenditure) with a variable infusion of exogenous insulin. After surgery, eight times more insulin was needed than before surgery (14.14 +/- 1.15 versus 1.78 +/- 0.29 pmol min-1 kg-1, P less than 0.001) to maintain euglycemia. 4. After surgery, stimulation of net carbohydrate oxidation (18.8 +/- 1.4 versus 17.2 +/- 1.8 mumol min-1 kg-1 preoperatively, not significant), suppression of lipolysis and lipid oxidation and inhibition of ketogenesis occurred to the same extent as before surgery. Of the infused nutrients, the glucose was all oxidized, amino acids replaced endogenous protein losses (= neutral nitrogen balance) and lipids were stored. Insulin administration caused no further increment in oxygen consumption or energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)
Preclinical Melanoma Imaging with <sup>68</sup>Ga-Labeled α-Melanocyte-Stimulating Hormone Derivatives Using PET (2017)

It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle<sup>4</sup>-cyclo[Asp<sup>5</sup>-His-D-Phe<sup>7</sup>-Arg-Trp-Lys<sup>10</sup>]-NH<sub>2</sub>, or Nle-CycMSH<sub>hex</sub>) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT). The goal of this study was to design and evaluate novel peptides for melanoma imaging with positron emission tomography (PET). We designed and synthesized three peptides, DOTA-PEG<sub>2</sub>-Nle-CycMSH<sub>hex</sub> (CCZ01047), DOTA-4-amino-(1-carboxymethyl) piperidine (Pip)-Nle-CycMSH<sub>hex</sub> (CCZ01048), and DOTA-Pip-Pip-Nle-CycMSH<sub>hex</sub> (CCZ01056). All three peptides exhibited high binding affinity to MC1R with sub-nanomolar K<sub>i</sub> values, rapid internalization into B16F10 melanoma cells and high <i>in vivo</i> stability with more than 93% remaining intact at 15 min post-injection (p.i.) in blood plasma. All three <sup>68</sup>Ga-labeled tracers produced high contrast PET images in C57BL/6J mice bearing B16F10 tumors, and their respective tumor uptakes were 8.0 ± 3.0, 12.3 ± 3.3, and 6.5 ± 1.4 %ID/g at 1 h p.i. Minimal normal organ activity was observed at 1 h p.i., except for kidneys (5.1 ± 1.4, 4.7 ± 0.5, and 6.2 ± 2.0 %ID/g, respectively), and thyroid (4.1 ± 0.6 %ID/g for CCZ01047 and 2.4 ± 0.6 %ID/g for CCZ01048). Due to high accumulation at tumor sites and rapid background clearance of <sup>68</sup>Ga-CCZ01048, we further evaluated it at 2 h p.i., and a tumor uptake of 21.9 ± 4.6 %ID/g was observed, with background activity further decreased. Exceptional image contrast was also achieved, i.e. tumor-to-blood, tumor-to-muscle, tumor-to-bone and tumor-to-kidney ratios were 96.4 ± 13.9, 210.9 ± 20.9, 39.6 ± 11.9 and 4.0 ± 0.9, respectively. A blocking study was also performed by co-injection of excess amount of non-radioactive Ga-coupled of CCZ01048, which confirmed that the tumor uptake was MC1R mediated. In conclusion, the introduction of a cationic Pip linker to Nle-CycMSH<sub>hex</sub>, CCZ01048, not only improved tumor uptake, but also generated high tumor-to-normal tissue contrast with PET imaging in a preclinical melanoma model. Therefore, CCZ01048 is a promising candidate for PET imaging of melanoma, and potentially as a theranostic agent for radionuclide therapy of melanoma when labeled with α or β emitters.
Novel Vesicular Approach For Topical Delivery of Baclofen Via Niosomes (2010)

Niosomes have been reported as a possible approach to improve the low skin penetration\nand bioavailability characteristics shown by conventional topical vehicle for Baclofen (centrally acting\nskeletal muscle relaxant). Niosomes were prepared by lipid film hydration method using non ionic surfactant\n(Span 20) and cholesterol in varying molar ratios such as 1:1, 1:2 and 2:1. The prepared systems were\ncharacterized for vesicle surface morphology, entrapment efficiency, Osmotic fragility and stability studies.\nThe in vitro drug release behavior was determined by an in-house fabricated dissolution-dialysis apparatus.\nThe skeletal muscle relaxant activity was determined by rota rod method using Swiss albino mice.\nThe average particle size of niosomes was in the range of 3260-3810 nm. The maximum percent drug entrapment\nwas observed with span 20 (89.67 ± 0.46 %). Furthermore, the release profile of baclofen from\nthese niosomes was 68.15 ± 1.7 % (maximum). The formulations kept for stability studies have exhibited\npercent drug entrapment value of 87.93 ± 0.34 % under refrigerated milieu (4 ± 2 °C). The mice treated\nwith formulations have shown improved muscle relaxation activity which was evident by increased number\nof falls in rota rod test as compared to plane drug treated mice (p value = 0.001).
Service robot localization using improved Particle filter (2008)

Recently, Particle filter becomes the most popular approach in mobile robot localization and has been applied with great success to a variety of state estimation problems. In this paper, the particle filter is applied in position tracking and global localization. Moreover, the posterior distribution of robot pose in global localization is usually multimodal due to the symmetry of the environment and ambiguous detected features. Considering these characteristics, we proposed the cluster particle filter to improve the global localization robustness and accuracy. Experiment results show the effectiveness and robustness of our approach in our service robot ApriAlpha™ Platform.
National burden of disease in India from indoor air pollution (2000)

In the last decade, a number of quantitative epidemiological studies of specific diseases have been done in developing countries that for the first time allow estimation of the total burden of disease (mortality and morbidity) attributable to use of solid fuels in adult women and young children, who jointly receive the highest exposures because of their household roles. Few such studies are available as yet for adult men or children over 5 years. This paper evaluates the existing epidemiological studies and applies the resulting risks to the more than three-quarters of all Indian households dependent on such fuels. Allowance is made for the existence of improved stoves with chimneys and other factors that may lower exposures. Attributable risks are calculated in reference to the demographic conditions and patterns of each disease in India. Sufficient evidence is available to estimate risks most confidently for acute respiratory infections (ARI), chronic obstructive pulmonary disease (COPD), and lung cancer. Estimates for tuberculosis (TB), asthma, and blindness are of intermediate confidence. Estimates for heart disease have the lowest confidence. Insufficient quantitative evidence is currently available to estimate the impact of adverse pregnancy outcomes (e.g., low birthweight and stillbirth). The resulting conservative estimates indicate that some 400-550 thousand premature deaths can be attributed annually to use of biomass fuels in these population groups. Using a disability-adjusted lost life-year approach, the total is 4-6% of the Indian national burden of disease, placing indoor air pollution as a major risk factor in the country.
Activation of SOCS-3 Messenger Ribonucleic Acid in the Hypothalamus by Ciliary Neurotrophic Factor (1999)

Ciliary neurotrophic factor (CNTF) is a neurocytokine expressed in glial cells that acts on brain cells to promote gene expression, survival, and differentiation. When administered systemically, CNTF reduces food intake and body weight in rodents. Genes encoding suppressors of cytokine signaling (SOCS) are induced by cytokines that activate membrane receptors in the same class as those that are activated by CNTF. We therefore examined the ability of CNTF to induce expression of socs genes in brain and peripheral tissues of rats and mice. Peripheral CNTF administration to ob/ob mice rapidly induced SOCS-3 messenger RNA (mRNA) in hypothalamus, as determined by Northern blotting and quantitative RT-PCR, but had no effect on cytokine-inducible sequence (CIS), SOCS-1, or SOCS-2 mRNA. In situ hybridization histochemistry of hypothalamus from ob/ob mice and normal rats demonstrated that CNTF induced SOCS-3 mRNA in the arcuate nucleus (Arc). Strong hybridization signals were also detected in the ependymal lining of the ventricles and the subfornical organ. This hybridization pattern was distinct from that resulting from peripheral leptin treatment with overlapping hybridization patterns only in the Arc. CNTF also induced expression of CIS, SOCS-1, SOCS-2, and SOCS-3 mRNA in the liver, and SOCS-2 and SOCS-3 mRNA in the kidney. CNTF induced SOCS-3 mRNA and SOCS-3 protein levels in an astrocyte cell line. Transient expression of SOCS-3, but not CIS or SOCS-2, inhibited CNTF-induced signal transduction in astrocytes. In conclusion, SOCS-3 mRNA is specifically induced by CNTF in regions of the hypothalamus that are both overlapping and distinct from that induced by leptin. Similar to leptin, the Arc is likely to be a direct target of CNTF, and this region may play a role in the body weight-reducing effects of CNTF. SOCS-3 is a negative regulator of CNTF signal transduction, and inhibitors of SOCS-3 function may enhance endogenous CNTF signaling after neuronal injury or enhance the body weight-reducing effect of CNTF after peripheral administration.
Heterologous expression of a cardiomyopathic myosin that is defective in its actin interaction. (1994)

A point mutation in the heavy chain of cardiac myosin, resulting in replacement of an arginine (Arg) with glutamine (Gln), has been linked to hypertrophic cardiomyopathy in humans (Geisterfer-Lowrance, A. A. T., Kass, S., Tanigawa, G., Vosberg, H.-P., McKenna, W., Seidman, J. G., and Seidman, C. E. (1990) Cell 62, 999-1006). To determine the functional impact of this mutation, baculovirus-driven coexpression of myosin heavy and light chains has been developed. The Arg-403-->Gln mutation resulted in cardiac myosin with normal ATPase activity in the absence of actin. However, in the presence of actin, ATPase activity was greatly reduced (Vmax decreased > 3.5-fold and K(app) increased > 3-fold). In vitro motility was reduced nearly 5-fold by this single amino acid mutation. Thus, Arg-403 likely contributes to an important interaction at the actin interface of myosin. Replacement of Arg-403 with Gln leads to decreased rate(s) of transition within the actin-myosin crossbridge cycle. In humans, this mutation will result in decreased power output per unit area of cardiac muscle, likely providing a stimulus for hypertrophy.
Formation of YSZ–SDC Solid Solution in a Nanocrystalline Heterophase System and Its Effect on the Electrical Conductivity (2005)

The stability of an yttria‐stabilized zirconia and samaria‐doped ceria (YSZ–SDC) nanocrystalline heterophase system was studied with in situ high‐temperature X‐ray diffraction during a simulated sintering program. Formation of YSZ–SDC solid solution in the nanocrystalline system was found to start at a low temperature between 900° and 950°C. The analysis of lattice parameters as a function of temperature suggested that YSZ and SDC species diffused mutually during the formation of solid solution. The electrical conductivity of the YSZ–SDC solid solution was significantly lower than that of the YSZ and SDC.
Comparison of simultaneous downhole and surface microseismic monitoring in the Williston Basin (2011)

Microseismic events reported from simultaneous downhole and surface monitoring of a hydraulic fracture well stimulation were matched on an event‐by‐event basis and compared. Downhole monitoring was much more sensitive than surface monitoring near the observation well, detecting 4–5 times the number of events, but the downhole monitoring appeared to be lose much of it sensitivity advantage at distances greater than about 3,000 feet. The picks reported from surface monitoring varied dramatically depending on the picking criteria that were used, which emphasizes the need for a reliable pick confidence factor. In the strict assessment of the surface data the existence of the majority of the events were corroborated by the downhole data, including many sub‐visible surface events. Considerable differences exist in the reported spatial location of the events picked by the two methods despite correct positioning of perforation shots for each method. The events picked by the surface method are clustered much more closely to the wellbore, which may represent a considerably lower estimate of the stimulated rock volume.
Exploratory analysis of job separations from supported employment for persons with traumatic brain injury (1991)

Thirty-eight consecutive separations from employment in a supported employment program for persons with traumatic brain injuries were examined. Five categories of reasons for separation were identified, in order of frequency reported: (1) issues related to the employment setting, (2) interpersonal relationship problems, (3) mental health problems and criminal activity, (4) other problems, and (5) economic layoffs. Excluding true layoffs (temporary suspension of work for economic reasons only), over three fourths of the separations involved more than one reason. Potential strategies for reducing the occurrence of the problem areas were discussed.
Muscle synergies as a predictive framework for the EMG patterns of new hand postures (2009)

Synchronous muscle synergies have been suggested as a framework for dimensionality reduction in muscle coordination. Many studies have shown that synergies form a descriptive framework for a wide variety of tasks. We examined if a muscle synergy framework could accurately predict the EMG patterns associated with untrained static hand postures, in essence, if they formed a predictive framework. Hand and forearm muscle activities were recorded while subjects statically mimed 33 postures of the American Sign Language alphabet. Synergies were extracted from a subset of training postures using non-negative matrix factorization and used to predict the EMG patterns of the remaining postures. Across the subject population, as few as 11 postures could form an eight-dimensional synergy framework that allowed for at least 90% prediction of the EMG patterns of all 33 postures, including trial-to-trial variations. Synergies were quite robust despite using different postures in the training set, and also despite using a varied number of postures. Estimated synergies were categorized into those which were subject-specific and those which were general to the population. Population synergies were sparser than the subject-specific synergies, typically being dominated by a single muscle. Subject-specific synergies were more balanced in the coactivation of multiple muscles. We suggest as a result that global muscle coordination may be a combination of higher order control of robust subject-specific muscle synergies and lower order control of individuated muscles, and that this control paradigm may be useful in the control of EMG-based technologies, such as artificial limbs and functional electrical stimulation systems.