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In utero exposure to the ubiquitous plasticizer, bisphenol A (BPA) is associated with offspring obesity. As adipogenesis is a critical factor contributing to obesity, we determined the effects of in vivo maternal BPA and in vitro BPA exposure on newborn adipose tissue at the stem-cell level. For in vivo studies, female rats received BPA before and during pregnancy and lactation via drinking water, and offspring were studied for measures of adiposity signals. For in vitro BPA exposure, primary pre-adipocyte cell cultures from healthy newborns were utilized. We studied pre-adipocyte proliferative and differentiation effects of BPA and explored putative signal factors which partly explain adipose responses and underlying epigenetic mechanisms mediated by BPA. Maternal BPA-induced offspring adiposity, hypertrophic adipocytes and increased adipose tissue protein expression of pro-adipogenic and lipogenic factors. Consistent with in vivo data, in vitro BPA exposure induced a dose-dependent increase in pre-adipocyte proliferation and increased adipocyte lipid content. In vivo and in vitro BPA exposure promotes the proliferation and differentiation of adipocytes, contributing to an enhanced capacity for lipid storage. These findings reinforce the marked effects of BPA on adipogenesis and highlight the susceptibility of stem-cell populations during early life with long-term consequence on metabolic homeostasis.
The error box of the unusual Gamma-Ray Burst of March 5, 1979 falls completely inside the optical and radio image of the Supernova Remnant N49 in the Large Magellanic Cloud. This region was observed twice in x-rays with the High Resolution Imager of the Einstein Observatory, six weeks and nearly two years after the Gamma-Ray Burst. We show the comparison between the two observations.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Following implementation of automatic end dates for antimicrobial orders to facilitate antimicrobial stewardship at a large, academic children’s hospital, no differences were observed in patient mortality, length of stay, or readmission rates, even among patients with documented bacteremia.
Observations of speckles in the scattering disk of the Vela pulsar are presented and speckle techniques for studying and circumventing scattering of radio waves by the turbulent interstellar plasma are discussed. The speckle pattern contains, in a hologrammatic fashion, complete information on the structure of the radio source as well as the distribution of the scattering material. Speckle observations of interstellar scattering of radio waves are difficult because of their characteristically short timescales (≈seconds) and narrow bandwidths (≈kHz). Here, we present first observations, taken at 13 cm wavelength with elements of the SHEVE VLBI network, of speckles in interstellar scattering.
We determined the protein expression of adipogenic transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) and its co-repressor and co-activator complexes in adipose tissue from the obese offspring of under- and over-nourished dams. Female rats were fed either a high-fat (60% kcal) or control (10% kcal) diet before mating, and throughout pregnancy and lactation (Mat-OB). Additional dams were 50% food-restricted from pregnancy day 10 to term [intrauterine growth-restricted (IUGR)]. Adipose tissue protein expression was analyzed in newborn and adult male offspring. Normal birth weight Mat-OB and low birth weight IUGR newborns had upregulated PPARγ with variable changes in co-repressors and co-activators. As obese adults, Mat-OB and IUGR offspring had increased PPARγ with decreased co-repressor and increased co-activator expression. Nutritionally programmed increased PPARγ expression is associated with altered expression of its co-regulators in the newborn and adult offspring. Functional studies of PPARγ co-regulators are necessary to establish their role in PPARγ-mediated programmed obesity.
Socio-behavioural factors and pathogens associated with childhood diarrhoea are of global public health concern. Our survey in 696 children aged ⩽2 years in rural West Bengal detected rotavirus as sole pathogen in 8% (17/199) of diarrhoeic stool specimens. Other organisms were detected along with rotavirus in 11% of faecal specimens. A third of the children with rotavirus diarrhoea, according to Vesikari score, had severe illness. The top four rotavirus genotypes were G9P (28%), G1P (19%), G2P (14%) and G8P (8%). In the multivariate model, the practice of ‘drawing drinking water by dipping a pot in the storage vessel’ [adjusted odds ratio (aOR) 2·21, 95% confidence interval (CI) 1·03–4·74, P = 0·041], and ‘children aged ⩽6 months with non-exclusive breastfeeding’ (aOR 2·07, 95% CI 1·1–3·82, P = 0·024) had twice the odds of having diarrhoea. Incidence of rotavirus diarrhoea was 24/100 child-years in children aged >6–18 months, 19/100 child-years in children aged >18–24 months and 5/100 child-years in those aged ⩽6 months. Results have translational implications for future interventions including vaccine development.
The fetal or early origins of adult disease hypothesis states that environmental factors, particularly nutrition, act in early life to program the risks for chronic diseases in adult life. As eating habits can be linked to the development of several diseases including obesity, diabetes and cardiovascular disease, it could be proposed that persistent food preferences across the life-span in people who were exposed to an adverse fetal environment may partially explain their increased risk to develop metabolic disease later in life. In this paper, we grouped the clinical and experimental evidence demonstrating that the fetal environment may impact the individual's food preferences. In addition, we review the feeding preferences development and regulation (homeostatic and hedonic pathways, the role of taste/olfaction and the reward/pleasure), as well as propose mechanisms linking early life conditions to food preferences later in life. We review the evidence suggesting that in utero conditions are associated with the development of specific food preferences, which may be involved in the risk for later disease. This may have implications in terms of public health and primary prevention during early ages.
Maternal undernutrition (MUN) results in growth-restricted newborns with reduced nephron numbers that is associated with increased risk of hypertension and renal disease. The total adult complement of nephrons is set during nephrogenesis suggesting that MUN affects the staged development of nephrons in as yet unknown manner. A possible cause may be the increased renal apoptosis; therefore, we investigated whether apoptotic signaling and cell death were increased in MUN rat kidneys. Pregnant rat dams were fed an ad libitum diet [control] or were 50% food restricted (MUN) starting at embryonic day (E) 10. Male offspring kidneys (n = 5 each, MUN and control) were analyzed for mRNA using quantitative PCR (E20) and for protein expression using Western blotting and immunohistochemistry (E20 and postnatal day 1, P1). Apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Upregulation of pro-apoptotic protein expression was detected at E20 (Fas receptor, caspase 9) and at P1 (caspase 3, Bax). The anti-apoptotic factor Bcl2 was significantly decreased in P1 kidneys. Kidney TUNEL showed apoptotic nuclei significantly increased in the P1 nephrogenic zone (MUN 3.3 + 0.3 v. C 1.6 + 0.5, P = 0.002). The majority of apoptotic nuclei co-localized to mesenchyme and pretubular aggregates in the nephrogenic zone. Differential regulation of apoptosis in mesenchyme and pretubular aggregates following parturition suggests a mechanism for nephropenia in gestational programming of the kidney.
An approximate late time solution to the dynamics of phase separation for a nonconserved ordering order parameter (ø) coupled to a stable conserved field (c) is presented. In the Halperin Hohenberg(1) classification scheme this model is known as Model C with a symmetric coupling between nonconserved and conserved fields. The different time dependences of long (i.e., domain size lengths ∼ power law in time) and short wavelength (i.e., interfacial lengths ∼ exponential decay in time) fluctuations imply a simple relationship between the two fields. In essence ø controls the growth of the long wavelength fluctuations, and c modifies the interfacial profile. Asymptotically the dynamic structure factor (Sø(k,t)≡<Ø(k,t)Ø*(k,t)>) for the nonconserved field is shown to scale in the form Sø(k,t) = tdnfø(ktn), with n = 1/2. Similarly the structure factor for the conserved field (Sc(k,t)) is shown to obey the scaling law Sc(k,t) = tdn−1fc(ktn), with n = 1/2. Explicit expressions for the scaling functions fc(z) and fø(z) are presented for arbitrary dimension. These predictions can be tested through scattering experiments.
This study explores the effect of pH on the chemical mechanical polishing (CMP) characteristics of copper in H2O2 and KIO3 based slurries under various dynamic and static conditions. High purity copper disc was used to study the dissolution and oxidation kinetics at various pH (2 to 10) with 5% H2O2 or 0.1M KIO3. Electrochemical techniques were used to investigate the dissolution/passivation behavior of Cu. The affected surface layers of the statically etched Cu-disc were investigated using X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM). In 5% H2O2, the Cu removal rate decreases with an increase in pH and reaches minimum at pH 6, and then increases under alkaline conditions. XPS results indicate that the surface oxide formed at various pH values was responsible for this CMP trend. However, with 0.1M KIO3, the CMP removal rates were found to be lower at pH 2. The maximum was observed at pH 4, then the removal rate decreased with the increase of pH. The lower value of removal rate at pH2 was due to the fast interaction between Cu and KIO3 and the precipitation of CuI on the pad, which makes the pad glassy, resulting in lowered removal rates. This was confirmed by XPS measurements. The decreased CMP removal rates when the pH is higher than 4 might be due to the weaker oxidation power of KIO3 with the increase of pH.
Copper metallization in sub-0.18 μm semiconductor devices is achieved by combining the dual damascence techniques followed by chemical mechanical planarization (CMP). Tantalum and its nitride have been identified as the diffusion barrier layer for copper metallization. However, the wide differences in properties between copper and tantalum layers result in selectivity problems during CMP process. The aim of this work is to obtain a better understanding on the slurry selectivity for copper and tantalum and to develop slurries with best selectivity performance. In this work, the effect of several chemical parameters (abrasive type, oxidizer type, concentration, pH etc.) was studied through static and dynamic tests using advanced electrochemical techniques and surface analysis techniques. The surface layers of the statically etched copper and tantalum discs were investigated using X-ray photoelectron spectroscopy (XPS) and surface planarity was studied using atomic force microscopy (AFM). Polishing rates results show that alumina-based slurry polished copper very well whereas tantalum removal rate was low. However, for the silica-based slurry the tantalum shows much higher removal rate than copper and better surface planarity was obtained.
The present investigation was focused on understanding of the oxidation, dissolution and modification of Cu surface in slurries at various pH using hydrogen peroxide as oxidizer, glycine as complexing agent and 3-amino-triazol (ATA) as inhibitor during Cu-CMP. The electrochemical process involved in the oxidative dissolution of copper was investigated by potentiodynamic polarization studies. Surface modification of copper was investigated using Xray photoelectron spectroscopy to understand the interaction of Cu-H2O2-glycine-ATA during CMP. In the absence of glycine and ATA, the copper removal rate is found to be high in a slurry with 5% H2O2 at pH 2, then it decreases with increasing pH and reaches the minimum at pH 6, it continuously increases at alkaline condition. In the presence of 0.01M glycine, the removal rate of copper decreases in acidic slurries while increases significantly in alkaline slurries. With the further addition of ATA, the copper removal rate was reduced. However, better surface planarity was obtained. The present investigation enhanced understanding of the mechanism of Cu CMP in the presence of oxidizer, complexing agent and inhibitor for formulation of a highly effective CMP-slurry.
Maternal under-nutrition (MUN) during gestation results in growth-restricted newborns with reduced glomerular number and subsequent hypertension. We investigated dysregulation of glial derived neurotrophic factor (GDNF) and MAPK–ERK (mitogen-activated protein kinase–extracellular signal-regulated protein kinase) signal pathway gene expression following MUN. MUN rats were 50% food restricted from embryonic day 10 till postnatal day 1. Kidneys were harvested at embryonic day (E)20, and postnatal days (P)1 and 21. Kidney protein expression was determined by Western blot. At E20, protein expression of growth factor receptor alpha 1 (GFRα1) and phosphorylated ERK1/2 and mitogen-activated protein kinase kinase (MEK)1/2 were reduced significantly, and immunohistochemistry confirmed reduction of phosphorylated ERK (pERK) with maintenance of pERK localization. Total MEK and ERK were unchanged. At P1, only GFRα1 and pERK1/2 were reduced significantly while at P21, expression of all growth factors except total MEK was unchanged. Total MEK was increased. Glomerular number was decreased by 19% in P21 kidneys and blood pressure was increased in 12-week-old rats. In conclusion, GDNF and MAPK–ERK signaling are dysregulated during active nephrogenesis in fetal and early newborn offspring kidneys in the MUN model. This may be a key mechanism in reduced offspring nephrogenesis and programmed hypertension.
We present a series of experimental results, and their interpretation,
connected to various aspects of the hydrodynamics of laser produced
plasmas. Experiments were performed using the Prague PALS iodine laser
working at 0.44 μm wavelength and irradiances up to a few
1014 W/cm2. By adopting large focal spots and
smoothed laser beams, the lateral energy transport and lateral expansion
have been avoided. Therefore we could reach a quasi one-dimensional regime
for which experimental results can be more easily and properly compared to
available analytical models.
This paper reviews the developments in reporting of traditional embedded value and summarises some of the reasons why this is now undergoing change. It considers the purpose of an embedded value calculation and the effect of differing attitudes to risk. It comments on the recently developed European Embedded Value Principles and sets out the main areas where scope remains to apply judgement.
The paper proposes the market-consistent embedded value framework as a way forward to help provide guidance in some of these areas, in particular on the choice of discount rate and on calibration of stochastic techniques used to value embedded options and guarantees. The paper recognises that market-consistent embedded values are in relative infancy and sets out areas for possible future development.
Background. Culture influences symptom presentation and help-seeking and may influence the general practitioner's assessment.
Methods. We recruited Punjabi and English GP attenders to a two-phase survey in London (UK) using the Amritsar Depression Inventory and the General Health Questionnaire as screening instruments. The Clinical Interview Schedule was the criterion measure. General practitioners completed Likert assessments.
Results. The second phase was completed by 209 Punjabi and 180 English subjects. The prevalence of common mental disorders was not influenced by culture. Punjabi cases more often had ‘poor concentration and memory’ and ‘depressive ideas’ but were not more likely to have somatic symptoms. General practitioners were more likely to assess Punjabis with common mental disorder as having ‘physical and somatic’ symptoms or ‘sub-clinical disorders’. Punjabi cases with depressive ideas were less likely to be detected compared with English ones. In comparison to English men, English women were under-detected by Asian general practitioners. Help-seeking English subjects were more likely to be correctly identified as cases.
Conclusions. The prevalence of common mental disorders and somatic symptoms does not differ across cultures. Among English subjects, general practitioners were more likely to identify correctly pure psychiatric illness and mixed pathology; but Punjabi subjects with common mental disorders were more often assessed as having ‘sub-clinical disorders’ and ‘physical and somatic’ disorders. English women were less well detected than English men. English help-seeking cases were more likely to be detected.
X-ray emission spectra in the 5–22 nm range were recorded
from planar and structured (meshlike groove surface) gold targets
at 45° and 90° to the laser axis. A laser beam of 10-ns
duration with EL ≤ 700 mJ and
1.06-μm wavelength was used for the experiment. Experimental
results indicate an enhanced X-ray yield from a structured target
as compared to a planar target under identical experimental conditions.
Increased X-ray emission is attributed to plasma confinement and the
possibility of conversion of kinetic energy into localized thermal
energy of the plasma. Results are analyzed explicitly on the incident