Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping. For each gene at each locus, we condensed the evidence into a prioritization score. Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top prioritized genes. At 8 loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3). Our analysis provides support for previously implicated genes at several AD GWAS loci, as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery

Nanosheet thickness-modulated MoS2 dielectric property evidenced by field-effect transistor performance

We report on the nanosheet-thickness effects on the performance of top-gate MoS2 field-effect transistors (FETs), which is directly related to the MoS2 dielectric constant. Our top-gate nanosheet FETs with 40 nm thin Al2O3 displayed at least an order of magnitude higher mobility than those of bottom-gate nanosheet FETs with 285 nm thick SiO2, benefiting from the dielectric screening by high-k Al2O3. Among the top-gate devices, the single-layered FET demonstrated the highest mobility of similar to 170 cm(2) V-1 s(-1) with 90 mV dec(-1) as the smallest subthreshold swing (SS) but the double-and triple-layered FETs showed only similar to 25 and similar to 15 cm(2) V-1 s(-1) respectively with the large SS of 0.5 and 1.1 V dec(-1). Such property degradation with MoS2 thickness is attributed to its dielectric constant increase, which could rather reduce the benefits from the top-gate high-k dielectric.open115353Nsciescopu

Estimated Time of Biomineralization in Developing Rat Incisors

published_or_final_versio

Mapping coherence in measurement via full quantum tomography of a hybrid optical detector

Quantum states and measurements exhibit wave-like --- continuous, or particle-like --- discrete, character. Hybrid discrete-continuous photonic systems are key to investigating fundamental quantum phenomena, generating superpositions of macroscopic states, and form essential resources for quantum-enhanced applications, e.g. entanglement distillation and quantum computation, as well as highly efficient optical telecommunications. Realizing the full potential of these hybrid systems requires quantum-optical measurements sensitive to complementary observables such as field quadrature amplitude and photon number. However, a thorough understanding of the practical performance of an optical detector interpolating between these two regions is absent. Here, we report the implementation of full quantum detector tomography, enabling the characterization of the simultaneous wave and photon-number sensitivities of quantum-optical detectors. This yields the largest parametrization to-date in quantum tomography experiments, requiring the development of novel theoretical tools. Our results reveal the role of coherence in quantum measurements and demonstrate the tunability of hybrid quantum-optical detectors.Comment: 7 pages, 3 figure

The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease

Background: Administrative data is often used to identify patients with chronic obstructive pulmonary disease (COPD), yet the validity of this approach is unclear. We sought to develop a predictive model utilizing administrative data to accurately identify patients with COPD. Methods: Sequential logistic regression models were constructed using 9573 patients with postbronchodilator spirometry at two Veterans Affairs medical centers (2003-2007). COPD was defined as: 1) FEV1/FVC <0.70, and 2) FEV1/FVC < lower limits of normal. Model inputs included age, outpatient or inpatient COPD-related ICD-9 codes, and the number of metered does inhalers (MDI) prescribed over the one year prior to and one year post spirometry. Model performance was assessed using standard criteria. Results: 4564 of 9573 patients (47.7%) had an FEV1/FVC < 0.70. The presence of ≥1 outpatient COPD visit had a sensitivity of 76% and specificity of 67%; the AUC was 0.75 (95% CI 0.74-0.76). Adding the use of albuterol MDI increased the AUC of this model to 0.76 (95% CI 0.75-0.77) while the addition of ipratropium bromide MDI increased the AUC to 0.77 (95% CI 0.76-0.78). The best performing model included: ≥6 albuterol MDI, ≥3 ipratropium MDI, ≥1 outpatient ICD-9 code, ≥1 inpatient ICD-9 code, and age, achieving an AUC of 0.79 (95% CI 0.78-0.80). Conclusion: Commonly used definitions of COPD in observational studies misclassify the majority of patients as having COPD. Using multiple diagnostic codes in combination with pharmacy data improves the ability to accurately identify patients with COPD.Department of Veterans Affairs, Health Services Research and Development (DHA), American Lung Association (CI- 51755-N) awarded to DHA, the American Thoracic Society Fellow Career Development AwardPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84155/1/Cooke - ICD9 validity in COPD.pd

Relationship between Environmental Phthalate Exposure and the Intelligence of School-Age Children

BACKGROUND: Concern over phthalates has emerged because of their potential toxicity to humans. OBJECTIVE: We investigated the relationship between the urinary concentrations of phthalate metabolites and children`s intellectual functioning. METHODS: This study enrolled 667 children at nine elementary schools in five South Korean cities. A cross-sectional examination of urine phthalate concentrations was performed, and scores on neuro-psychological tests were obtained from both the children and their mothers. RESULTS: We measured mono-2-ethylhexyl phthalate (MEHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), both metabolites of di(2-ethylhexyl)phthalate (DEHP), and mono-n-butyl phthalate (MBP), a metabolite of dibutyl phthalate (DBP), in urine samples. The geometric mean (ln) concentrations of MEHP, MEOHP, and MBP were 21.3 mu g/L [geometric SD (GSD) = 2.2 mu g/L; range, 0.5-445.4], 18.0 mu g/L (GSD = 2.4; range, 0.07-291.1), and 48.9 mu g/L (GSD = 2.2; range, 2.1-1645.5), respectively. After adjusting for demographic and developmental covariates, the Full Scale IQ and Verbal IQ scores were negatively associated with DEHP metabolites but not with DBP metabolites. We also found a significant negative relationship between the urine concentrations of the metabolites of DEHP and DBP and children`s vocabulary subscores. After controlling for maternal IQ, a significant inverse relationship between DEHP metabolites and vocabulary subscale score remained. Among boys, we found a negative association between increasing MEHP phthalate concentrations and the sum of DEHP metabolite concentrations and Wechsler Intelligence Scale for Children vocabulary score; however, among girls, we found no significant association between these variables. CONCLUSION: Controlling for maternal IQ and other covariates, the results show an inverse relationship between phthalate metabolites and IQ scores; however, given the limitations in cross-sectional epidemiology, prospective studies are needed to fully explore these associations.This work was funded by the Eco-Technopia 21 project of Korea Institute of Environmental Science and Technology (091-081-059).Cho SC, 2010, J CHILD PSYCHOL PSYC, V51, P1050, DOI 10.1111/j.1469-7610.2010.02250.xKim BN, 2009, BIOL PSYCHIAT, V66, P958, DOI 10.1016/j.biopsych.2009.07.034Tanida T, 2009, TOXICOL LETT, V189, P40, DOI 10.1016/j.toxlet.2009.04.005Ghisari M, 2009, TOXICOL LETT, V189, P67, DOI 10.1016/j.toxlet.2009.05.004Barnett JH, 2009, AM J PSYCHIAT, V166, P909, DOI 10.1176/appi.ajp.2009.08081251Kim Y, 2009, NEUROTOXICOLOGY, V30, P564, DOI 10.1016/j.neuro.2009.03.012Engel SM, 2009, NEUROTOXICOLOGY, V30, P522, DOI 10.1016/j.neuro.2009.04.001Kamrin MA, 2009, J TOXICOL ENV HEAL B, V12, P157, DOI 10.1080/10937400902729226Brown JS, 2009, SCHIZOPHRENIA BULL, V35, P256, DOI 10.1093/schbul/sbm147Bellinger DC, 2008, NEUROTOXICOLOGY, V29, P828, DOI 10.1016/j.neuro.2008.04.005Wolff MS, 2008, ENVIRON HEALTH PERSP, V116, P1092, DOI 10.1289/ehp.11007van Neerven S, 2008, PROG NEUROBIOL, V85, P433, DOI 10.1016/j.pneurobio.2008.04.006Hatch EE, 2008, ENVIRON HEALTH-GLOB, V7, DOI 10.1186/1476-069X-7-27Zevalkink J, 2008, J GENET PSYCHOL, V169, P72Kolarik B, 2008, ENVIRON HEALTH PERSP, V116, P98, DOI 10.1289/ehp.10498SATHYANARAYANA S, 2008, CURR PROBL PEDIAT AD, V38, P34KHO YL, 2008, J ENV HLTH SCI, V34, P271Huang PC, 2007, HUM REPROD, V22, P2715, DOI 10.1093/humrep/dem205Janjua NR, 2007, ENVIRON SCI TECHNOL, V41, P5564, DOI 10.1021/es0628755Meeker JD, 2007, ENVIRON HEALTH PERSP, V115, P1029, DOI 10.1289/ehp.9852Fromme H, 2007, INT J HYG ENVIR HEAL, V210, P21, DOI 10.1016/j.ijheh.2006.09.005Xu Y, 2007, ARCH TOXICOL, V81, P57, DOI 10.1007/s00204-006-0143-8Pereira C, 2007, ACTA HISTOCHEM, V109, P29, DOI 10.1016/j.acthis.2006.09.008Hauser R, 2006, EPIDEMIOLOGY, V17, P682, DOI 10.1097/01.ede.0000235996.89953.d7Zhu DF, 2006, BRAIN, V129, P2923, DOI 10.1093/brain/awl215Andrade AJM, 2006, TOXICOLOGY, V227, P185, DOI 10.1016/j.tox.2006.07.022Lottrup G, 2006, INT J ANDROL, V29, P172, DOI 10.1111/j.1365-2605.2005.00642.xBreous E, 2005, MOL CELL ENDOCRINOL, V244, P75, DOI 10.1016/j.mce.2005.06.009Wenzel A, 2005, MOL CELL ENDOCRINOL, V244, P63, DOI 10.1016/j.mce.2005.02.008Kato K, 2005, ANAL CHEM, V77, P2985, DOI 10.1021/ac0481248Tanaka T, 2005, FOOD CHEM TOXICOL, V43, P581, DOI 10.1016/j.fct.2005.01.001Duty SM, 2005, HUM REPROD, V20, P604, DOI 10.1093/humrep/deh656Kota BP, 2005, PHARMACOL RES, V51, P85, DOI 10.1016/j.phrs.2004.07.012Hays T, 2005, CARCINOGENESIS, V26, P219, DOI 10.1093/carcin/bgh285Hauser R, 2004, ENVIRON HEALTH PERSP, V112, P1734, DOI 10.1289/ehp.7212Bornehag CG, 2004, ENVIRON HEALTH PERSP, V112, P1393, DOI 10.1289/ehp.7187Ishido M, 2004, J NEUROCHEM, V91, P69, DOI 10.1111/j.1471-4159.2004.02696.xMink PJ, 2004, EPIDEMIOLOGY, V15, P385, DOI 10.1097/01.ede.0000128402.86336.7eBellinger DC, 2004, EPIDEMIOLOGY, V15, P383, DOI 10.1097/01.ede.0000129525.15064.a4Shea KM, 2003, PEDIATRICS, V111, P1467Tanaka T, 2002, FOOD CHEM TOXICOL, V40, P1499, DOI 10.1016/S0278-6915(02)00073-XHoppin JA, 2002, ENVIRON HEALTH PERSP, V110, P515SATTLER JM, 2001, ASSESSMENT CHILDRENRice D, 2000, ENVIRON HEALTH PERSP, V108, P511Bellinger DC, 2000, NEUROTOXICOL TERATOL, V22, P133LIM YR, 2000, KOR J CLIN PSYCHOL, V19, P563Braissant O, 1998, ENDOCRINOLOGY, V139, P2748Peters JM, 1997, CARCINOGENESIS, V18, P2029Baldini IM, 1997, PROG NEURO-PSYCHOPH, V21, P925Roberts RA, 1997, FUND APPL TOXICOL, V38, P107PARK KS, 1996, DEV KEDI WISC INDIVIMONZANI F, 1993, CLIN INVESTIGATOR, V71, P367SILVERSTEIN AB, 1990, J CLIN PSYCHOL, V46, P333HINTON RH, 1986, ENVIRON HEALTH PERSP, V70, P195KIM MK, 1986, SEOUL J PSYCHIAT, V11, P194KAUFMAN AS, 1976, CONTEMP EDUC PSYCHOL, V1, P1801

Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

10.1186/1752-1947-5-131Journal of Medical Case Reports513

Pseudo-acetylation of multiple sites on human Tau proteins alters Tau phosphorylation and microtubule binding, and ameliorates amyloid beta toxicity

Tau is a microtubule-associated protein that is highly soluble and natively unfolded. Its dysfunction is involved in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD), where it aggregates within neurons. Deciphering the physiological and pathogenic roles of human Tau (hTau) is crucial to further understand the mechanisms leading to its dysfunction in vivo. We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo

Correlation between Discharged Worms and Fecal Egg Counts in Human Clonorchiasis

Clonorchiasis is a major neglected disease in East Asia. Worm data in infected humans are very limited, and only egg counts roughly estimate infection burden of the worms. In endemic areas, we recruited infected cases and tried to collect the adult worms from them. They were treated with 3 doses of praziquantel, and purged next day under fasting. Adult worms of C. sinensis were recovered from their diarrheal feces. The worms discharged from humans after treatment are minimum confirmed numbers. The worm recovery rate noticeably increased in subjects with higher egg counts. The number of collected worms was well-correlated with the egg counts. Worm collection by praziquantel medication and purgation is a safe non-invasive method to get worm information from human. The present study confirms that at least 110 worms are infected in a human body with egg counts per gram of feces around 3,000, and egg productivity of a worm per day is around 4,000

Hepatitis B vaccinations among Koreans: Results from 2005 Korea National Cancer Screening Survey

<p>Abstract</p> <p>Background</p> <p>Liver cancer is one of most commonly diagnosed cancers among Koreans. Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer. HBV infection can be prevented by effective screening and vaccination programs. The purpose of this study is to examine the status of HBV infection and the predictors associated with HBV vaccination.</p> <p>Methods</p> <p>The study population was derived from the 2005 Korea National Cancer Screening Survey (KNCSS). The KNCSS is an annual cross-sectional survey that uses a nationally-representative random sampling to investigate cancer screening rates. A total of 1,786 Koreans over 40 years of age participated in this study.</p> <p>Results</p> <p>Of all the participants, 5.9% reported HBV positive (HBsAg+, HBsAb-), 41.8% were HBV negative but protected (HBsAg-, HBsAb+), and 52.3% were unprotected (HBsAg-, HBsAb-). Among unprotected individuals (n = 934), 23.1% reported to have received the vaccination. About half of those who had vaccinations completed the 3-shot vaccine series. In multiple analyses, education, having private cancer insurance, alcohol use, having regular check-up, and doing regular exercise were associated with completed HBV vaccination.</p> <p>Conclusion</p> <p>This study result suggests that we need a liver cancer education program to increase HBV awareness and to increase the liver cancer prevention message among low educated populations.</p