Miracle-dz/UniFAR-FTUs huggingface dataset:
Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans.

RATIONALE Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism. OBJECTIVES To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers. METHODS Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach. MEASUREMENTS AND MAIN RESULTS Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation-derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans. CONCLUSIONS As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials. gov (NCT 01492517).
TRISOMY 8 AS THE COMMONEST ADDITIONAL CHROMOSOMAL ABNORMALITY IN PHILADELPHIA POSITIVE CHRONIC MYELOGENOUS LEUKEMIA

Introduction The aim of our study was to observe the presence of additional abnormalities and their relative frequencies in chronic myelogenous leukemia and correlate their clinical and prognostic importance in CML. Methods 66 cases of CML were included in the study. History taking, clinical examination and relevant laboratory test of all the cases were done. Bone marrow and peripheral blood sample were collected and culture of these samples using suitable medium was done. Karyotyping was done manually as well as with the help of cytovision software. Results Additional chromosomal abnormalities along with Philadelphia chromosome were observed in 7 cases (13.5%) out of 52 reported karyograms. Trisomy 8 was the most common additional abnormality observed (3 cases, 42.9%). It was seen as an isolated additional abnormality in 2 cases while in 1 case trisomy 8 was present in association with other chromosomal abnormalities. Chronic stage of CML was documented in 2 of the patients showing trisomy 8 while one patient had blastic phase of CML. Discussion The commonest additional chromosomal abnormality observed in CML is trisomy of chromosome 8. Trisomy 8 and other abnormalities affecting the 8q24 region are very important, because this includes the gene locus for the c-Myc gene. C-Myc is a key player in cell growth and differentiation and a correlation between high c-Myc expression and CML progression has been reported. Our results have re-emphasized the importance of trisomy 8 and its role in the pathogenesis of CML.
Response to physical activity programs and their effects on health behavior.

EVALUATION of the overall effectiveness of health programs concerned with disease prevention and health enhancement requires examination of the factors that influence response to such programs, as well as of the changes in health attitudes and behavior that they generate. We have given specific attention to these issues in regard to pr;ograms of supervised physical activity for middle-aged men considered at risk of coronary heart disease. Data were obtained as part of a collaborative research effort which included pilot studies at the Universities of Minnesota, Wisconsin, and Pennsylvania State in 1966-68. These studies, supported by the Heart Disease and Stroke Control Program of the Public Health Service, were designed primarily to examine the relationship between physical activity and changes in cardiovascular risk. The research effort was coordinated by the Steering Committee on Co-operative Pilot Studies of Physical Activity and Coronary Heart Disease, comprised of Dr. Henry L. Taylor, chairman, Dr. Richard Remington, director of the statistical center, Dr. Ellsworth Buskirk, Dr. Bruno Balke, Dr. Samuel Fox III, Dr. Jeremiah Stamler, and Dr. Frederick Epstein. Dr. Taylor (Laboratory of Physiological Hygiene, University of Minnesota, Minneapolis) and co-authors have prepared a report outlining the nature of this research effort, which includes a discussion of the physiological effects of the physical activity programs. The pilot studies provided an opportunity to systematically examine the factors influencing response to this kind of health program as well as the behavioral effects of participation. These issues were explored in line with a broader research focus dealing with determinants of health behavior and of health behavior change (1). The design of the pilot studies made it possible to examine these issues on a prospective and longitudinal basis. This type of research approach serves a necessary and useful function in expanding the body of social science theory and research data dealing with health behavior (2-4). The study groups included in this research effort were selected from a metropolitan community-Minneapolis, Minn. -and from university settings that included both faculty members and service employees-Madison, Wis. , and College Park, Pa. All persons participating in the programs were sedentary men 45-59 years At the time of the study, Dr. Heinzelmann was chief of behavioral science activities and Mr. Bagley was a research assistant with the Heart Disease and Stroke Control Program, Regional Medical Pro,grams Service, Health Services and Mental Health Administration. Dr. Heinzelmann is now with the National Institute of Law Enforcement and Criminal Justice, Department of Justice. Mr. Bagley is currently employed in California.
Maximum likelihood for Bayesian estimator based on /spl alpha/-stable for image

A maximum likelihood for Bayesian estimator based on /spl alpha/-stable is discussed. Closer to a realistic situation, and unlike previous methods used for the Bayesian estimator, for the case discussed here it is not necessary to know the variance of the noise. The parameters relative to Bayesian estimators of the model built up are carefully investigated after a discussion of /spl alpha/-stable 3D simulations for a maximum likelihood. The Bayesian estimator then is established. As an example, an improved Bayesian estimator that is a natural extension of the Wiener solution and other wavelet denoising (soft and hard threshold methods), is presented to illustrate our discussion.
The effect of intracarotid epinephrine, norepinephrine, and angiotensin on the regional cerebral blood flow in man

In recent years there has been renewed ininterest in the possible role of the autonomic nervous system in the regulation of cerebral blood flow. Histochemical techniques have clearly shown the abundant network of autonomic nerves around the basal and pial arteries of the brain. ' Electron-microscopic studies have confirmed that these nerves terminate in contact with the vascular smooth muscles in the same way as in other organs where the physiologic importance of the autonomic nerves is well est a b l i ~ h e d . ' ~ L o c a l appl ica t ion of catecholamines has been shown t o constrict the basal and pial cerebral and this response can be blocked pharmac~logica l ly . ~ >7 Despite these achievements the effect of circulating catecholamines is not yet clear, as will be reviewed below in the Discussion. Circulating catecholamines might well play a n important role in the pathogenesis of cerebral vasospasm as seen in subarachnoid hemorrhage and presumably also in the initial phase of a migraine attack. The drugs still are used in the treatment of shock and the regulation of blood pressure during anesthesia. In these situations a cerebral vasoconstrictor effect would be highly disadvantageous. On this basis it was considered pertinent to derive data of clinical relevance regarding the effects of circulating catecholamines on the cerebral blood flow. In the present study cerebral blood flow was measured simultaneously in multiple small areas of the brain of nonanesthetized man during direct intracarotid infusion of the drugs.
Characterization of Human Glycogenin-2, a Self-glucosylating Initiator of Liver Glycogen Metabolism*

Glycogenin-2 is a recently described self-glucosylating protein potentially involved in the initiation of glycogen biosynthesis (Mu, J., Skurat, A. V., and Roach, P. J. (1997) J. Biol. Chem. 272, 27589–27597). In human liver extracts, most of the glycogenin-2 was only detectable after treatment with α-amylase. Similarly, purifed highM r glycogen was only detected after release by α-amylase treatment. Based on analysis by polymerase chain reaction, the predominant isoform in liver was glycogenin-2β. Glycogenin-2 was found in Ewing’s sarcoma RD-ES cells where, however, it was not associated with high M r carbohydrate. Both human liver and human RD-ES cell extracts also contained glycogenin-1. Glycogenin-1 and glycogenin-2 interact with one another, based onin vitro interactions and co-immunoprecipitation from liver and cell extracts. Mutation of Tyr-196 in glycogenin-2 to a Phe residue abolished the ability of glycogenin-2 to self-glucosylate but not to interact with glycogenin-1. Stable overexpression of glycogenin-2α in Rat-1 fibroblast cells resulted in a 5-fold increase in the level of glycogen present in the low speed pellet but little change in the low speed supernatant. This result is important since it indicates that the level of glycogenin-2 can determine glycogen accumulation and hence has the potential to control glycogen synthesis.
Diffuse bony metastases at presentation in a child with glioblastoma multiforme: A case report

At initial diagnosis, an 11‐year‐old girl with glioblastoma multiforme (GBM) presented with diffuse osteoblastic metastases. Primary brain tumors rarely metastasize outside of the central nervous system (CNS) without prior neurosurgery. Extracranial spread at diagnosis has been previously documented in just two adults. Extracranial metastasis of a childhood glioma without prior neurosurgery at any time during the course of the disease is exceedingly rare. Spread to bone by gliomas is also infrequent, and when they occur, bony metastases are usually isolated to one or two sites in any given patient. The widespread osseous metastases in our patient have been reported in three prior cases of highgrade gliomas. This child's GBM likely reflects a highly aggressive variant with the potential to spread outside the CNS and with a predilection for bone. Oncologists should be aware that GBM may present in this fashion during childhood.
Identification of Epithelial to Mesenchymal Transition as a Novel Source of Fibroblasts in Intestinal Fibrosis*

Intestinal fibrosis is a major complication of Crohn disease (CD), but the precise mechanism by which it occurs is incompletely understood. As a result, specific therapies to halt or even reverse fibrosis have not been explored. Here, we evaluated the contribution of epithelial to mesenchymal transition (EMT) to intestinal fibrosis associated with a mouse model of CD and also human inflammatory bowel disease. Mice administered intrarectal 2,4,6-trinitrobenzene sulfonic acid (TNBS) develop inflammation and fibrosis that resembles CD both histologically and by immunologic profile. We utilized this model to molecularly probe the contribution of EMT to intestinal fibrosis. Additionally, we utilized double-transgenic VillinCre;R26Rosa-lox-STOP-lox-LacZ mice, in which removal of the STOP cassette by Cre recombinase in villin+ intestinal epithelial cells activates permanent LacZ expression, to lineage trace epithelial cells that might undergo EMT upon TNBS administration. TNBS-induced fibrosis is associated with the presence of a significant number of cells that express both epithelial and mesenchymal markers. In the lineage tagged transgenic mice, the appearance of LacZ+ cells that also express the fibroblast marker FSP1 unequivocally demonstrates EMT. Transforming growth factor (TGF)-β1, a known inducer of EMT in epithelial cells, induces EMT in rat intestinal epithelial cells in vitro, and bone morphogenic protein-7, an antagonist of TGF-β1, inhibits EMT and fibrosis both in vitro and in the TNBS-treated mice. Our study demonstrates that EMT contributes to intestinal fibrosis associated with the TNBS-induced model of Crohn colitis and that inhibition of TGF-β1 with recombinant human bone morphogenic protein-7 prevents this process and prevents fibrosis.
Dynamics and structure of the vertical ionospheric disturbances caused by Tohoku earthquake according to Irkutsk bistatic CHIRP-sounding

In the work we present results of observation of the mid-scale vertical ionospheric irregularities caused by Tohoku earthquake (11/03/2011, 05:47UT) at distance 3400km from epicenter with 1 minute temporary resolution. Their spatial and temporary dynamics is also investigated. As showed the analysis of the experimental data, the main response of the ionosphere was observed at Irkutsk from 06:10UT to 07:00UT. Short-term variations of the electron density profile were also observed from 06:00UT. This corresponds to the main horizontal speed of disturbances about 4, 2-2.5 and 1.2-1.3 km/s. The vertical scale of the irregularities was 10-20 km. Irregularities practically weren't observed at heights above 180200km.
Mutations of Bacteriophage T4 59 Helicase Loader Defective in Binding Fork DNA and in Interactions with T4 32 Single-stranded DNA-binding Protein*

Bacteriophage T4 gene 59 protein greatly stimulates the loading of the T4 gene 41 helicase in vitro and is required for recombination and recombination-dependent DNA replication in vivo. 59 protein binds preferentially to forked DNA and interacts directly with the T4 41 helicase and gene 32 single-stranded DNA-binding protein. The helicase loader is an almost completely α-helical, two-domain protein, whose N-terminal domain has strong structural similarity to the DNA-binding domains of high mobility group proteins. We have previously speculated that this high mobility group-like region may bind the duplex ahead of the fork, with the C-terminal domain providing separate binding sites for the fork arms and at least part of the docking area for the helicase and 32 protein. Here, we characterize several mutants of 59 protein in an initial effort to test this model. We find that the I87A mutation, at the position where the fork arms would separate in the model, is defective in binding fork DNA. As a consequence, it is defective in stimulating both unwinding by the helicase and replication by the T4 system. 59 protein with a deletion of the two C-terminal residues, Lys216 and Tyr217, binds fork DNA normally. In contrast to the wild type, the deletion protein fails to promote binding of 32 protein on short fork DNA. However, it binds 32 protein in the absence of DNA. The deletion is also somewhat defective in stimulating unwinding of fork DNA by the helicase and replication by the T4 system. We suggest that the absence of the two terminal residues may alter the configuration of the lagging strand fork arm on the surface of the C-terminal domain, so that it is a poorer docking site for the helicase and 32 protein.
FETAL AND NEONATAL ERYTHROPOIESIS *

The regulation of red cell production in the adult animal has been shown to be governed, at least in part, by oxygen-dependent erythropoietin production by the ‘kidney. In rodents the degree of dependency on renally produced erythropoietin approaches the absolute. ’ Thus the nephrectomized rat or mouse has almost complete suppression of red cell production. Changes in the oxygen supplydemand relationship have been shown to have a profound effect upon the rate of erythropoiesis. It is to be noted, however, that such perturbations in high order mammal^^,^ do not produce as marked a change in red cell production as that in the rodent. The question has been raised as to whether regulation of erythropoiesis in fetal and neonatal life is the same as that for the “ a d ~ l t ” ~ TO answer this question, the evolution of the erythron and its regulation have been studied in the fetal and neonatal rat, which is a relatively immature animal in comparison with human beings at birth, and in the guinea pig, an animrl.1 in which the degree of maturity at birth approaches that of the human being. These data will be briefly summarized and are reviewed extensively e l~ewhere . ~
Case control study of women treated with chemotherapy for breast cancer during pregnancy as compared with nonpregnant patients with breast cancer.

BACKGROUND The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer. METHODS From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used. RESULTS Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28-19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%-82.1%) for pregnant patients and 57% (95% CI: 46.7%-65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%-80.3%) for pregnant patients and 59% (95% CI: 49.1%-67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%-86.4%) for pregnant patients and 71% (95% CI: 61.1%-78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade. CONCLUSIONS For patients who received chemotherapy during pregnancy, survival was comparable to-if not better than-that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.
Label‐fusion‐segmentation and deformation‐based shape analysis of deep gray matter in multiple sclerosis: The impact of thalamic subnuclei on disability

Deep gray matter (DGM) atrophy has been reported in patients with multiple sclerosis (MS) already at early stages of the disease and progresses throughout the disease course. We studied DGM volume and shape and their relation to disability in a large cohort of clinically well‐described MS patients using new subcortical segmentation methods and shape analysis. Structural 3D magnetic resonance images were acquired at 1.5 T in 118 patients with relapsing remitting MS. Subcortical structures were segmented using a multiatlas technique that relies on the generation of an automatically generated template library. To localize focal morphological changes, shape analysis was performed by estimating the vertex‐wise displacements each subject must undergo to deform to a template. Multiple linear regression analysis showed that the volume of specific thalamic nuclei (the ventral nuclear complex) together with normalized gray matter volume explains a relatively large proportion of expanded disability status scale (EDSS) variability. The deformation‐based displacement analysis confirmed the relation between thalamic shape and EDSS scores. Furthermore, white matter lesion volume was found to relate to the shape of all subcortical structures. This novel method for the analysis of subcortical volume and shape allows depicting specific contributions of DGM abnormalities to neurological deficits in MS patients. The results stress the importance of ventral thalamic nuclei in this respect. Hum Brain Mapp 35:4193–4203, 2014. © 2014 Wiley Periodicals, Inc.
A naturalistic study of the production of causal connectives by children

ABSTRACT This study analysed the naturalistic productions of because and so by 96 children, vaged 3; 6–9; 6, vwhile vnarrating real, vpersonal events. Few semantic errors could be construed as evidence of confused thinking; none is a confusion vdescribed by Piaget. Of the vsemantically correct causal uses, 81 % encode psychological causality, mostly statements of other people's intentions. Other analyses revealed: (1) many of the relationships encoded are highly predictable, (2) virtually all causality occurred prior to the time of narration, (3) age trends are remarkably absent, (4) because and so are used in significantly different ways even by the youngest children, (5) only eight sentences showed a vreversal of the appropriate order of cause and effect. The discrepancy between the last finding and many other laboratory studies vwhich find many such reversals may be due to the fact that children are causally linking strictly successive events only 32 % of the time; for the rest, they are encoding events that partially or completely overlap in time.
Relative resistance of pigs to infection by natural aerosols of FMD virus

The author would like to thank H. H. Sheikh Zayed Bin Sultan Al Nahyan, President of the United Arab Emirates, and H. H. Sheikh Tahnoon Bin Zayed Al Nahyan, Chairman of the Private Department, for the great support they extended to this paper. The author also thanks Mr A. Pohl for help with sampling the birds, Mrs M. Ibrahim for the laboratory work, and Mr A. Azeez, Mr A. Rasheed, Mr Yousuf and Mr Noushat for feeding and observing the falcons. Special thanks are due to N. Harcourt-Brown for proofreading the manuscript and all his advice.
Time‐gated total internal reflection fluorescence spectroscopy (TG‐TIRFS): application to the membrane marker laurdan

A novel setup for total internal reflection fluorescence microscopy with spectral and temporal (nanosecond) resolution was used to measure the emission spectra of the membrane marker laurdan either selectively within the plasma membrane or in whole living cells, depending on the incident angle of the excitation light. With increasing temperature, the intensity of the fluorescence band around 490 nm increased in comparison with the band around 440 nm, which has previously been assigned to a phase transition of membrane lipids from gel to liquid crystalline phase. For a better separation of the overlapping spectral bands, time‐gated detection with a delay of 10–15 ns with respect to the exciting laser pulse was used. As a parameter of membrane dynamics the so‐called generalized polarization GP = (I440 − I490)/(I440 + I490) was evaluated at temperatures between 24 and 41 °C and variable angles of the incident light permitting to excite laurdan molecules either within the plasma membrane or in the whole cell. A decrease of the GP values by ≈ 0.2 units between 28 and 41 °C indicated an increase in membrane fluidity or a decrease in membrane stiffness with increasing temperature. In addition, higher GP values were observed for the plasma membrane as compared with intracellular membranes, probably due to a higher amount of cholesterol. Because properties of the plasma membrane have a large influence on the uptake or release of certain pharmaceutical agents or metabolites, the direct assessment of the dynamics of the plasma membrane by total internal reflection fluorescence spectroscopy appears to be important for pharmacology.