270 research outputs found

    Topological Surface States Protected From Backscattering by Chiral Spin Texture

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    Topological insulators are a new class of insulators in which a bulk gap for electronic excitations is generated by strong spin orbit coupling. These novel materials are distinguished from ordinary insulators by the presence of gapless metallic boundary states, akin to the chiral edge modes in quantum Hall systems, but with unconventional spin textures. Recently, experiments and theoretical efforts have provided strong evidence for both two- and three-dimensional topological insulators and their novel edge and surface states in semiconductor quantum well structures and several Bi-based compounds. A key characteristic of these spin-textured boundary states is their insensitivity to spin-independent scattering, which protects them from backscattering and localization. These chiral states are potentially useful for spin-based electronics, in which long spin coherence is critical, and also for quantum computing applications, where topological protection can enable fault-tolerant information processing. Here we use a scanning tunneling microscope (STM) to visualize the gapless surface states of the three-dimensional topological insulator BiSb and to examine their scattering behavior from disorder caused by random alloying in this compound. Combining STM and angle-resolved photoemission spectroscopy, we show that despite strong atomic scale disorder, backscattering between states of opposite momentum and opposite spin is absent. Our observation of spin-selective scattering demonstrates that the chiral nature of these states protects the spin of the carriers; they therefore have the potential to be used for coherent spin transport in spintronic devices.Comment: to be appear in Nature on August 9, 200

    Transactivation of EGFR by LPS induces COX-2 expression in enterocytes

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    Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC

    Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects.

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    The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ⩾30 kg m−2 and binge eating scale scores ⩾19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day−1 GSK1521498, 5 mg day−1 GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day−1 caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day−1 on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation

    Quantifying geocode location error using GIS methods

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    BACKGROUND: The Metropolitan Atlanta Congenital Defects Program (MACDP) collects maternal address information at the time of delivery for infants and fetuses with birth defects. These addresses have been geocoded by two independent agencies: (1) the Georgia Division of Public Health Office of Health Information and Policy (OHIP) and (2) a commercial vendor. Geographic information system (GIS) methods were used to quantify uncertainty in the two sets of geocodes using orthoimagery and tax parcel datasets. METHODS: We sampled 599 infants and fetuses with birth defects delivered during 1994–2002 with maternal residence in either Fulton or Gwinnett County. Tax parcel datasets were obtained from the tax assessor's offices of Fulton and Gwinnett County. High-resolution orthoimagery for these counties was acquired from the U.S. Geological Survey. For each of the 599 addresses we attempted to locate the tax parcel corresponding to the maternal address. If the tax parcel was identified the distance and the angle between the geocode and the residence were calculated. We used simulated data to characterize the impact of geocode location error. In each county 5,000 geocodes were generated and assigned their corresponding Census 2000 tract. Each geocode was then displaced at a random angle by a random distance drawn from the distribution of observed geocode location errors. The census tract of the displaced geocode was determined. We repeated this process 5,000 times and report the percentage of geocodes that resolved into incorrect census tracts. RESULTS: Median location error was less than 100 meters for both OHIP and commercial vendor geocodes; the distribution of angles appeared uniform. Median location error was approximately 35% larger in Gwinnett (a suburban county) relative to Fulton (a county with urban and suburban areas). Location error occasionally caused the simulated geocodes to be displaced into incorrect census tracts; the median percentage of geocodes resolving into incorrect census tracts ranged between 4.5% and 5.3%, depending upon the county and geocoding agency. CONCLUSION: Geocode location uncertainty can be estimated using tax parcel databases in a GIS. This approach is a viable alternative to global positioning system field validation of geocodes

    Effects of Dopamine on Sensitivity to Social Bias in Parkinson's Disease

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    Patients with Parkinson's disease (PD) sometimes develop impulsive compulsive behaviours (ICBs) due to their dopaminergic medication. We compared 26 impulsive and 27 non-impulsive patients with PD, both on and off medication, on a task that examined emotion bias in decision making. No group differences were detected, but patients on medication were less biased by emotions than patients off medication and the strongest effects were seen in patients with ICBs. PD patients with ICBs on medication also showed more learning from negative feedback and less from positive feedback, whereas off medication they showed the opposite effect

    Malaria prevention in north-eastern Tanzania: patterns of expenditure and determinants of demand at the household level

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    OBJECTIVE: This study aims to provide a better understanding of the amounts spent on different malaria prevention products and the determinants of these expenditures. METHODS: 1,601 households were interviewed about their expenditure on malaria mosquito nets in the past five years, net re-treatments in the past six months and other expenditures prevention in the past two weeks. Simple random sampling was used to select villages and streets while convenience sampling was used to select households. Expenditure was compared across bed nets, aerosols, coils, indoor spraying, using smoke, drinking herbs and cleaning outside environment. FINDINGS: 68% of households owned at least one bed net and 27% had treated their nets in the past six months. 29% were unable to afford a net. Every fortnight, households spent an average of US 0.18onnetsandtheirtreatment,constitutingabout470.18 on nets and their treatment, constituting about 47% of total prevention expenditure. Sprays, repellents and coils made up 50% of total fortnightly expenditure (US0.21). Factors positively related to expenditure were household wealth, years of education of household head, household head being married and rainy season. Poor quality roads and living in a rural area had a negative impact on expenditure. CONCLUSION: Expenditure on bed nets and on alternative malaria prevention products was comparable. Poor households living in rural areas spend significantly less on all forms of malaria prevention compared to their richer counterparts. Breaking the cycle between malaria and poverty is one of the biggest challenges facing malaria control programmes in Africa

    Photoperiod Regulates Lean Mass Accretion, but Not Adiposity, in Growing F344 Rats Fed a High Fat Diet

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    yesIn this study the effects of photoperiod and diet, and their interaction, were examined for their effects on growth and body composition in juvenile F344 rats over a 4-week period. On long (16L:8D), relative to short (8L:16D), photoperiod food intake and growth rate were increased, but percentage adiposity remained constant (ca 3-4%). On a high fat diet (HFD), containing 22.8% fat (45% energy as fat), food intake was reduced, but energy intake increased on both photoperiods. This led to a small increase in adiposity (up to 10%) without overt change in body weight. These changes were also reflected in plasma leptin and lipid levels. Importantly while both lean and adipose tissue were strongly regulated by photoperiod on a chow diet, this regulation was lost for adipose, but not lean tissue, on HFD. This implies that a primary effect of photoperiod is the regulation of growth and lean mass accretion. Consistent with this both hypothalamic GHRH gene expression and serum IGF-1 levels were photoperiod dependent. As for other animals and humans, there was evidence of central hyposomatotropism in response to obesity, as GHRH gene expression was suppressed by the HFD. Gene expression of hypothalamic AgRP and CRH, but not NPY nor POMC, accorded with the energy balance status on long and short photoperiod. However, there was a general dissociation between plasma leptin levels and expression of these hypothalamic energy balance genes. Similarly there was no interaction between the HFD and photoperiod at the level of the genes involved in thyroid hormone metabolism (Dio2, Dio3, TSHβ or NMU), which are important mediators of the photoperiodic response. These data suggest that photoperiod and HFD influence body weight and body composition through independent mechanisms but in each case the role of the hypothalamic energy balance genes is not predictable based on their known function.Scottish Government (Rural and Environment Science and Analytical Services Division, http://www.scotland.gov.uk/), AWR LR LMT PJM and the BBSRC, (http://www.bbsrc.ac.uk/home/home.aspx, grant BB/K001043/1), AWR GH PJ
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