Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma.

Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling

Are you a researcher as well as a medical illustrator?

When we list the areas of practice for medical illustrators we always include research, but how involved in research are we? The aim of this activity is to encourage your professional development not just as a medical illustrator but your involvement with research whether that is undertaking your own research, undertaking evidence based practice (1) , working as part of a research team, advising researchers on the value of medical illustration or supporting a student undertaking a research project for their degree or post-graduate qualification

Hinode/Extreme-Ultraviolet Imaging Spectrometer Observations of the Temperature Structure of the Quiet Corona

We present a Differential Emission Measure (DEM) analysis of the quiet solar corona on disk using data obtained by the Extreme-ultraviolet Imaging Spectrometer (EIS) on {\it Hinode}. We show that the expected quiet Sun DEM distribution can be recovered from judiciously selected lines, and that their average intensities can be reproduced to within 30%. We present a subset of these selected lines spanning the temperature range $\log$ T = 5.6 to 6.4 K that can be used to derive the DEM distribution reliably. The subset can be used without the need for extensive measurements and the observed intensities can be reproduced to within the estimated uncertainty in the pre-launch calibration of EIS. Furthermore, using this subset, we also demonstrate that the quiet coronal DEM distribution can be recovered on size scales down to the spatial resolution of the instrument (1$"$ pixels). The subset will therefore be useful for studies of small-scale spatial inhomogeneities in the coronal temperature structure, for example, in addition to studies requiring multiple DEM derivations in space or time. We apply the subset to 45 quiet Sun datasets taken in the period 2007 January to April, and show that although the absolute magnitude of the coronal DEM may scale with the amount of released energy, the shape of the distribution is very similar up to at least $\log$ T $\sim$ 6.2 K in all cases. This result is consistent with the view that the {\it shape} of the quiet Sun DEM is mainly a function of the radiating and conducting properties of the plasma and is fairly insensitive to the location and rate of energy deposition. This {\it universal} DEM may be sensitive to other factors such as loop geometry, flows, and the heating mechanism, but if so they cannot vary significantly from quiet Sun region to region.Comment: Version accepted by ApJ and published in ApJ 705. Abridged abstrac

Southwestern Pottery and Turquoise in Northeastern Texas

Rare and often questionable occurrences of southwestern pottery and turquoise artifacts have been reported in northeastern Texas. These artifacts may mark major interaction networks. Both southwestern pottery and turquoise artifacts have been found at the Sanders site, which is located in the core distribution of these erratics

The Seasonal Cycle and Interannual Variability in Stratospheric Temperatures and Links to the Brewer–Dobson Circulation: An Analysis of MSU and SSU Data

Previous studies have shown that lower-stratosphere temperatures display a near-perfect cancellation between tropical and extratropical latitudes on both annual and interannual time scales. The out-of-phase relationship between tropical and high-latitude lower-stratospheric temperatures is a consequence of variability in the strength of the Brewer–Dobson circulation (BDC). In this study, the signal of the BDC in stratospheric temperature variability is examined throughout the depth of the stratosphere using data from the Stratospheric Sounding Unit (SSU). While the BDC has a seemingly modest signal in the annual cycle in zonal-mean temperatures in the mid- and upper stratosphere, it has a pronounced signal in the month-to-month and interannual variability. Tropical and extratropical temperatures are significantly negatively correlated in all SSU channels on interannual time scales, suggesting that variations in wave driving are a major factor controlling global-scale temperature variability not only in the lower stratosphere (as shown in previous studies), but also in the mid- and upper stratosphere. The out-of-phase relationship between tropical and high latitudes peaks at all levels during the cold-season months: December–March in the Northern Hemisphere and July–October in the Southern Hemisphere. In the upper stratosphere, the out-of-phase relationship with high-latitude temperatures extends beyond the tropics and well into the extratropics of the opposite hemisphere. The seasonal cycle in stratospheric temperatures follows the annual march of insolation at all levels and latitudes except in the mid- to upper tropical stratosphere, where it is dominated by the semiannual oscillation. M

Microelectronics Process Engineering at San Jose State University: A Manufacturing-Oriented Interdisciplinary Degree Program

San Jose State University\u27s new interdisciplinary curriculum in Microelectronics Process Engineering is described. This baccalaureate program emphasizes hands-on thin-film fabrication experience, manufacturing methods such as statistical process control, and fundamentals of materials science and semiconductor device physics. Each course of the core laboratory sequence integrates fabrication knowledge with process engineering and manufacturing methods. The curriculum development process relies on clearly defined and detailed program and course learning objectives. We also briefly discuss our strategy of making process engineering experiences accessible for all engineering students through both Lab Module and Statistics Module series

Investigation of generic hub fairing and pylon shapes to reduce hub drag

Reported are investigations of fairing configurations pointed toward substantially reducing hub drag. Experimental investigations have shown the importance of hub-fairing camber, lower-surface curvature, and relative size of the drag. The significance of pylon and hub fairings in combination have also been shown. Model test data presented here documented these findings, and also showed the effect of gaps and hub-fairing inclination angle on drag. From a drag standpoint, the best hub fairing had a circular arc, upper-surface curvature, a flat bottom surface, and 8.75% camber

Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the diagnosis of dementia within community dwelling populations

<b>Background</b><p></p> Various tools exist for initial assessment of possible dementia with no consensus on the optimal assessment method. Instruments that use collateral sources to assess change in cognitive function over time may have particular utility. The most commonly used informant dementia assessment is the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE).<p></p> A synthesis of the available data regarding IQCODE accuracy will help inform cognitive assessment strategies for clinical practice, research and policy.<p></p> <b>Objectives</b><p></p> Our primary objective was to determine the diagnostic accuracy of the informant based questionnaire IQCODE, for detection of all cause (undifferentiated) dementia in community-dwelling adults with no previous cognitive assessment. We sought to describe the accuracy of IQCODE (the index test) against a clinical diagnosis of dementia (the reference standard).<p></p> Our secondary objective was to describe the effect of heterogeneity on the summary estimates. We were particularly interested in the traditional 26-item scale versus the 16-item short form; and language of administration. We explored the effect of varying the threshold IQCODE score used to define 'test positivity'.<p></p> <b>Search methods</b><p></p> We searched the following sources on 28 January 2013: ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), BIOSIS Previews (ISI Web of Knowledge), Web of Science with Conference Proceedings (ISI Web of Knowledge), LILACS (BIREME). We also searched sources relevant or specific to diagnostic test accuracy: MEDION (Universities of Maastrict and Leuven); DARE (York University); ARIF (Birmingham University). We used sensitive search terms based on MeSH terms and other controlled vocabulary.<p></p> <b>Selection criteria</b><p></p> We selected those studies performed in community settings that used (not necessarily exclusively) the IQCODE to assess for presence of dementia and, where dementia diagnosis was confirmed, with clinical assessment. Our intention with limiting the search to a 'community' setting was to include those studies closest to population level assessment. Within our predefined community inclusion criteria, there were relevant papers that fulfilled our definition of community dwelling but represented a selected population, for example stroke survivors. We included these studies but performed sensitivity analyses to assess the effects of these less representative populations on the summary results.<p></p> <b>Data collection and analysis</b><p></p> We screened all titles generated by the electronic database searches and abstracts of all potentially relevant studies were reviewed. Full papers were assessed for eligibility and data extracted by two independent assessors. For quality assessment (risk of bias and applicability) we used the QUADAS 2 tool. We included test accuracy data on the IQCODE used at predefined diagnostic thresholds. Where data allowed, we performed meta-analyses to calculate summary values of sensitivity and specificity with corresponding 95% confidence intervals (CIs). We pre-specified analyses to describe the effect of IQCODE format (traditional or short form) and language of administration for the IQCODE.<p></p> <b>Main results</b><p></p> From 16,144 citations, 71 papers described IQCODE test accuracy. We included 10 papers (11 independent datasets) representing data from 2644 individuals (n = 379 (14%) with dementia). Using IQCODE cut-offs commonly employed in clinical practice (3.3, 3.4, 3.5, 3.6) the sensitivity and specificity of IQCODE for diagnosis of dementia across the studies were generally above 75%.<p></p> Taking an IQCODE threshold of 3.3 (or closest available) the sensitivity was 0.80 (95% CI 0.75 to 0.85); specificity was 0.84 (95% CI 0.78 to 0.90); positive likelihood ratio was 5.2 (95% CI 3.7 to 7.5) and the negative likelihood ratio was 0.23 (95% CI 0.19 to 0.29).<p></p> Comparative analysis suggested no significant difference in the test accuracy of the 16 and 26-item IQCODE tests and no significant difference in test accuracy by language of administration. There was little difference in sensitivity across our predefined diagnostic cut-points.<p></p> There was substantial heterogeneity in the included studies. Sensitivity analyses removing potentially unrepresentative populations in these studies made little difference to the pooled data estimates. The majority of included papers had potential for bias, particularly around participant selection and sampling. The quality of reporting was suboptimal particularly regarding timing of assessments and descriptors of reproducibility and inter-observer variability.<p></p> <b>Authors' conclusions</b><p></p> Published data suggest that if using the IQCODE for community dwelling older adults, the 16 item IQCODE may be preferable to the traditional scale due to lesser test burden and no obvious difference in accuracy. Although IQCODE test accuracy is in a range that many would consider 'reasonable', in the context of community or population settings the use of the IQCODE alone would result in substantial misdiagnosis and false reassurance. Across the included studies there were issues with heterogeneity, several potential biases and suboptimal reporting quality

Functionalization of Bacterial Microcompartment Shell Proteins With Covalently Attached Heme.

Heme is a versatile redox cofactor that has considerable potential for synthetic biology and bioelectronic applications. The capacity to functionalize non-heme-binding proteins with covalently bound heme moieties in vivo could expand the variety of bioelectronic materials, particularly if hemes could be attached at defined locations so as to facilitate position-sensitive processes like electron transfer. In this study, we utilized the cytochrome maturation system I to develop a simple approach that enables incorporation of hemes into the backbone of target proteins in vivo. We tested our methodology by targeting the self-assembling bacterial microcompartment shell proteins, and inserting functional hemes at multiple locations in the protein backbone. We found substitution of three amino acids on the target proteins promoted heme attachment with high occupancy. Spectroscopic measurements suggested these modified proteins covalently bind low-spin hemes, with relative low redox midpoint potentials (about -210 mV vs. SHE). Heme-modified shell proteins partially retained their self-assembly properties, including the capacity to hexamerize, and form inter-hexamer attachments. Heme-bound shell proteins demonstrated the capacity to integrate into higher-order shell assemblies, however, the structural features of these macromolecular complexes was sometimes altered. Altogether, we report a versatile strategy for generating electron-conductive cytochromes from structurally-defined proteins, and provide design considerations on how heme incorporation may interface with native assembly properties in engineered proteins

Serotyping of Toxoplasma gondii Infection Using Peptide Membrane Arrays.

The intracellular parasite Toxoplasma gondii can cause chronic infections in most warm-blooded animals, including humans. In the USA, strains belonging to four different Toxoplasma clonal lineages (types 1, 2, 3, and 12) are commonly isolated, whereas strains not belonging to these lineages are predominant in other continents such as South America. Strain type plays a pivotal role in determining the severity of Toxoplasma infection. Therefore, it is epidemiologically relevant to develop a non-invasive and inexpensive method for determining the strain type in Toxoplasma infections and to correlate the genotype with disease outcome. Serological typing is based on the fact that many host antibodies are raised against immunodominant parasite proteins that are highly polymorphic between strains. However, current serological assays can only reliably distinguish type 2 from non-type 2 infections. To improve these assays, mouse, rabbit, and human infection serum were reacted against 950 peptides from 62 different polymorphic Toxoplasma proteins by using cellulose membrane peptide arrays. This allowed us to identify the most antigenic peptides and to pinpoint the most relevant polymorphisms that determine strain specificity. Our results confirm the utility of previously described peptides and identify novel peptides that improve and increase the specificity of the assay. In addition, a large number of novel proteins showed potential to be used for Toxoplasma diagnosis. Among these, peptides derived from several rhoptry, dense granule, and surface proteins represented promising candidates that may be used in future experiments to improve Toxoplasma serotyping. Moreover, a redesigned version of the published GRA7 typing peptide performed better and specifically distinguished type 3 from non-type 3 infections in sera from mice, rabbits, and humans