265 research outputs found

    Enantioselective Total Synthesis of (-)-Nardoaristolone B via a Gold(I)-Catalyzed Oxidative Cyclization

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    The first enantioselective total synthesis of (−)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis

    A Data Mining Perspective of XRF Elemental Analysis from Pueblo People’s Pottery

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    Hierarchical clustering was used to identify elemental signatures in artifacts attributed to the Pueblo peoples. The artifacts in this study are pottery samples found at different sites in the state of New Mexico, USA. Three methods were applied: complete, average, and Ward. Their corresponding cophenetic correlation coefficients were used to contrast the three methods. Elemental characterization was only based on X-ray fluorescence excitation from a portable spectrometer with the silver anode. The elemental correlations here disclosed by data mining techniques are expected to guide further archaeological studies and assist experts in the assessment of provenance and historical ethnographic studies. XRF elemental analysi

    Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders

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    Autism spectrum disorders (ASD) are highly heritable and genetically complex conditions. Although highly penetrant mutations in multiple genes have been identified, they account for the etiology of <1/3 of cases. There is also strong evidence for environmental contribution to ASD, which can be mediated by still poorly explored epigenetic modifications. We searched for methylation changes on blood DNA of 53 male ASD patients and 757 healthy controls using a methylomic array (450K Illumina), correlated the variants with transcriptional alterations in blood RNAseq data, and performed a case-control association study of the relevant findings in a larger cohort (394 cases and 500 controls). We found 700 differentially methylated CpGs, most of them hypomethylated in the ASD group (83.9%), with cis-acting expression changes at 7.6% of locations. Relevant findings included: (1) hypomethylation caused by rare genetic variants (meSNVs) at six loci (ERMN, USP24, METTL21C, PDE10A, STX16 and DBT) significantly associated with ASD (q-value <0.05); and (2) clustered epimutations associated to transcriptional changes in single-ASD patients (n = 4). All meSNVs and clustered epimutations were inherited from unaffected parents. Resequencing of the top candidate genes also revealed a significant load of deleterious mutations affecting ERMN in ASD compared with controls. Our data indicate that inherited methylation alterations detectable in blood DNA, due to either genetic or epigenetic defects, can affect gene expression and contribute to ASD susceptibility most likely in an additive manner, and implicate ERMN as a novel ASD gene

    Temperature Effects in the Composition of Metal Halide Perovskite thin Films

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    Metal halide perovskites have shown to be a structure with great promise as an efficient photovoltaic, but at the same time it is affected by instability problems that degrade their performance. Degradation mechanisms vary with temperature, moisture, oxidation, and energy conversion during light exposure. We study performance loss due to temperature by probing diffusion of elemental composition across the thickness of films produced by spin coating and for temperatures ranging from 20 to 200°C. X-ray reflectivity was used to identify the electron density, composition, and quality of the films, aided with X-ray fluorescence and X-ray photoelectron spectroscopy studies to obtain information about degradation of the organic phase of the films

    Development and initial validation of a computer-administered health literacy assessment in Spanish and English: FLIGHT/VIDAS.

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    Current measures of health literacy have been criticized on a number of grounds, including use of a limited range of content, development on small and atypical patient groups, and poor psychometric characteristics. In this paper, we report the development and preliminary validation of a new computer-administered and -scored health literacy measure addressing these limitations. Items in the measure reflect a wide range of content related to health promotion and maintenance as well as care for diseases. The development process has focused on creating a measure that will be useful in both Spanish and English, while not requiring substantial time for clinician training and individual administration and scoring. The items incorporate several formats, including questions based on brief videos, which allow for the assessment of listening comprehension and the skills related to obtaining information on the Internet. In this paper, we report the interim analyses detailing the initial development and pilot testing of the items (phase 1 of the project) in groups of Spanish and English speakers. We then describe phase 2, which included a second round of testing of the items, in new groups of Spanish and English speakers, and evaluation of the new measure\u27s reliability and validity in relation to other measures. Data are presented that show that four scales (general health literacy, numeracy, conceptual knowledge, and listening comprehension), developed through a process of item and factor analyses, have significant relations to existing measures of health literacy

    Hepatitis B Virus Variants with Multiple Insertions and/or Deletions in the X Open Reading Frame 3 ' End: Common Members of Viral Quasispecies in Chronic Hepatitis B Patients

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    Hepatitis B virus; Insertions; Next-generation sequencingVirus de l'hepatitis B; Insercions; Seqüenciació de nova generacióVirus de la hepatitis B; Inserciones; Secuenciación de próxima generaciónDeletions in the 3′ end region of the hepatitis B virus (HBV) X open reading frame (HBX) may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions (Indels) in this region in the quasispecies of 50 chronic hepatitis B (CHB) patients without HCC. We identified 103 different Indels in 47 (94%) patients, in a median of 3.4% of their reads (IQR, 1.3–8.4%), and 25% (IQR, 13.1–40.7%) of unique sequences identified in each quasispecies (haplotypes). Of those Indels, 101 (98.1%) caused 44 different altered stop codons, the most commonly observed were at positions 128, 129, 135, and 362 (putative position). Moreover, 39 (37.9%) Indels altered the TATA-like box (TA) sequences of Cp; the most commonly observed caused TA2 + TA3 fusion, creating a new putative canonical TATA box. Four (8%) patients developed negative clinical outcomes after a median follow-up of 9.4 (8.7–12) years. In conclusion, we observed variants with Indels in the HBX 3′ end in the vast majority of our CHB patients, some of them encoding alternative versions of HBx with potential functional roles, and/or alterations in the regulation of transcription.This research was funded by Instituto de Salud Carlos III and co-financed by the European Regional Development Fund (ERDF), grant number PI18/01436; PI19/00301; and by the Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297. The APC was funded by the grant PI18/01436
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