93 research outputs found

    Similarity of Traveling-Wave Delays in the Hearing Organs of Humans and Other Tetrapods

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    Transduction of sound in mammalian ears is mediated by basilar-membrane waves exhibiting delays that increase systematically with distance from the cochlear base. Most contemporary accounts of such “traveling-wave” delays in humans have ignored postmortem basilar-membrane measurements in favor of indirect in vivo estimates derived from brainstem-evoked responses, compound action potentials, and otoacoustic emissions. Here, we show that those indirect delay estimates are either flawed or inadequately calibrated. In particular, we argue against assertions based on indirect estimates that basilar-membrane delays are much longer in humans than in experimental animals. We also estimate in vivo basilar-membrane delays in humans by correcting postmortem measurements in humans according to the effects of death on basilar-membrane vibrations in other mammalian species. The estimated in vivo basilar-membrane delays in humans are similar to delays in the hearing organs of other tetrapods, including those in which basilar membranes do not sustain traveling waves or that lack basilar membranes altogether

    Loci influencing blood pressure identified using a cardiovascular gene-centric array

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    Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.</p

    Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

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    In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

    The third annual joint scientific symposium of NIH/FDA CAA and Washington DC Chapter of SCBA

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    Hydrothermal growth of TiO2 nanorod arrays and in situ conversion to nanotube arrays for highly efficient quantum dot-sensitized solar cells

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    TiO2 nanorod (NR) and nanotube (NT) arrays grown on transparent conductive substrates are attractive electrode for solar cells. In this paper, TiO2 NR arrays are hydrothermally grown on FTO substrate, and are in situ converted into NT arrays by hydrothermally etching. The TiO2 NR arrays are reported as single crystalline, but the TiO2 NR arrays are demonstrated to be polycrystalline with a bundle of 2–5 nm single crystalline nanocolumns grown along [001] throughout the whole NR from bottom to top. TiO2 NRs can be converted to NTs by hydrothermal selective etching of the (001) core and remaining the inert sidewall of (110) face. A growth mechanism of the NR and NT arrays is proposed. Quantum dot-sensitized solar cells (QDSCs) are fabricated by coating CdSe QDs on to the TiO2 arrays. After conversion from NRs to NTs, more QDs can be filled in the NTs and the energy conversion efficiency of the QDSCs almost double

    Low-Temperature Growth of SnO2 Nanorod Arrays and Tunable n-p-n Sensing Response of a ZnO/SnO2 Heterojunction for Exclusive Hydrogen Sensors

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    Uniform SnO2 nanorod arrays have been deposited at low temperature by plasma-enhanced chemical vapor deposition (PECVD). ZnO surface modification is used to improve the selectivity of the SnO2 nanorod sensor to H2 gas. The ZnO-modified SnO2 nanorod sensor shows a normal n-type response to 100 ppm CO, NH3, and CH4 reducing gas whereas it exhibits concentration-dependent n-p-n transitions for its sensing response to H2 gas. This abnormal sensing behavior can be explained by the formation of n-ZnO/p-Zn-O-Sn/n-SnO2 heterojunction structures. The gas sensors can be used in highly selective H2 sensing and this study also opens up a general approach for tailoring the selectivity of gas sensors by surface modification. Uniform SnO2 nanorod arrays have been deposited by PECVD and highly selective H2 sensors are fabricated by ZnO surface modification of the SnO2 nanorod arrays. Concentration-dependent n-p-n transitions for the sensing response to H2 gas in the range of 10-3000 ppm are observed owing to the formation of n-ZnO/p-Zn-O-Sn/n-SnO2 heterojunction structures

    Classification of CT Brain Images of Head Trauma

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    Abstract. A method for automatic classification of computed tomography (CT) brain images of different head trauma types is presented in this paper. The method has three major steps: 1. The images are first segmented to find potential hemorrhage regions using ellipse fitting, background removal and wavelet decomposition technique; 2. For each region, features (such as area, major axis length, etc.) are extracted; 3. Each extracted feature is classified using machine learning algorithm; the images are then classified based on its component regions’ classification. The automatic medical image classification will be useful in building a content-based medical image retrieval system.
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