Cochlin, Intraocular Pressure Regulation and Mechanosensing

Fluid shear modulates many biological properties. How shear mechanosensing occurs in the extracellular matrix (ECM) and is transduced into cytoskeletal change remains unknown. Cochlin is an ECM protein of unknown function. Our investigation using a comprehensive spectrum of cutting-edge techniques has resulted in following major findings: (1) over-expression and down-regulation of cochlin increase and decrease intraocular pressure (IOP), respectively. The overexpression was achieved in DBA/2J-Gpnmb+/SjJ using lentiviral vectors, down-regulation was achieved in glaucomatous DBA/2J mice using targeted disruption (cochlin-null mice) and also using lentiviral vector mediated shRNA against cochlin coding region; (2) reintroduction of cochlin in cochlin-null mice increases IOP; (3) injection of exogenous cochlin also increased IOP; (4) increasing perfusion rates increased cochlin multimerization, which reduced the rate of cochlin proteolysis by trypsin and proteinase K; The cochlin multimerization in response to shear stress suggests its potential mechanosensing. Taken together with previous studies, we show cochlin is involved in regulation of intraocular pressure in DBA/2J potentially through mechanosensing of the shear stress

Early glandular neoplasia of the lung

Although bronchogenic carcinomas progress through a very well defined sequence of metaplasia, dysplasia and carcinoma in situ, very little is known about the early progression of glandular neoplasms of the lung. In particular, the early precursor lesion from which fully malignant adenocarcinomas arise has effectively eluded recognition, at least until recently. Several lines of evidence now implicate atypical adenomatous hyperplasia (AAH) as an initial morphologic stage in multistep lung tumorigenesis. Despite its small size, AAH can be appreciated at the light microscopic level and characterized at the molecular genetic level. Indeed, the genetic characterization of AAH promises to further our understanding of lung cancer development and might facilitate the design of novel strategies for early detection of lung cancer

Institutional risk factors for norovirus outbreaks in Hong Kong elderly homes: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Most of the institutional outbreaks of norovirus in Hong Kong occur in elderly homes, the proportion being 69% in 2006. Residents in elderly homes are a special population seriously affected by norovirus infections, it is necessary to investigate the risk factors of the norovirus outbreaks in Hong Kong elderly homes at the facility level.</p> <p>Methods</p> <p>A cohort of 748 elderly homes was followed up from January 2005 to December 2007; each elderly home was treated as one observation unit and the outcome event was the norovirus outbreak. Cox regression models were fitted to estimate the rate ratio (RR) and 95% confidence interval (CI) for the potential risk factors.</p> <p>Results</p> <p>A total of 276 norovirus outbreaks were confirmed during the study period; the outbreak rate was 12.2 (95% CI: 9.9-14.6) per 100 home-years; elderly homes with a larger capacity (RR = 1.4, 95% CI: 1.3-1.5 (per 30-resident increment)), a higher staff-to-resident ratio (RR = 1.2, 95% CI: 1.1-1.3 (per 1/30 increment) and better wheelchair accessibility (RR = 2.0, 95% CI: 1.3-3.2) were found to have an elevated norovirus outbreak rate in Hong Kong elderly homes; Elderly homes with partitions between beds had a lower rate of norovirus outbreaks (RR = 0.6, 95% CI: 0.4-0.8).</p> <p>Conclusions</p> <p>Elderly home capacity, staff-to-resident ratio and wheelchair accessibility were risk factors for norovirus outbreaks in Hong Kong elderly homes. Partitions between beds were a protective factor of norovirus outbreaks. These results should be considered in the infection control in Hong Kong elderly homes.</p

Association of temporal factors and suicides in the United States, 2000–2004

The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Fuzzy clustering analysis in environmental impact assessment - A complement tool to environmental quality index

In spite of rapid progress achieved in the methodological research underlying environmental impact assessment (EIA), the problem of weighting various parameters has not yet been solved. This paper presents a new approach, fuzzy clustering analysis, which is illustrated with an EIA case study on Baoshan-Wusong District in Shanghai, China. Fuzzy clustering analysis may be used whenever a composite classification of environmental quality/impact incorporates multiple parameters. In such cases the technique may be used as a complement or an alternative to comprehensive assessment. In fuzzy clustering analysis, the classification is determined by a fuzzy relation. After a fuzzy similarity matrix has been established and the fuzzy relation stabilized, a dynamic clustering chart can be developed. Given a suitable threshold, the appropriate classification can be accomplished. The methodology is relatively simple and the results can be interpreted to provide valuable information to support decision making and improve management of the environment. © 1993 Kluwer Academic Publishers

A COMPLEMENTARY TOOL TO WATER QUALITY INDEX: FUZZY CLUSTERING ANALYSIS

ABSTRACT: A general methodology for fuzzy clustering analysis is developed and illustrated with a case study of water quality evaluation for Dianshan Lake, Shanghai, China. Fuzzy clustering analysis may be used whenever a composite classification of water quality incorporates multiple parameters. In such cases, the technique may be used as a complement or an alternative to comprehensive assessment. In fuzzy clustering analysis, the classification is determined by a fuzzy relation. After a fuzzy similarity matrix has been established and the fuzzy relation stabilized, a dynamic clustering chart can be developed. Given a suitable threshold, the appropriate classification is worked out. The methodology is relatively simple, and the results can be interpreted to provide valuable information to support decision making and to aid water quality management. Copyright © 1992, Wiley Blackwell. All rights reserve

Generation of multi-octave-spanning laser harmonics by cascaded quasi-phase matching in a monolithic ferroelectric crystal

We report the generation of the second to the sixth harmonics of a fundamental frequency covering two and a half octaves in a multiply-periodically poled lithium tantalate crystal by cascaded quasi-phase-matched frequency mixing. A frequency comb that is composed of these harmonics will permit the synthesis of a train of periodic subcycle subfemtosecond pulses in a compact setting. , by mixing pulses from a mode-locked laser with pulses from a synchronously pumped optical parametric oscillator (OPO) where m is the comb frequency spacing, 0 is a static offset phase, and m is the phase difference between adjacent comb components; q is an integer with value from a few for the Raman approach to tens of thousands for the mode-locked lasers approaches. Equation A common approach to generating laser harmonics is phase-matched harmonic generation and mixing using birefringent crystals. Owing to the nature of phase matching the harmonics are phase coherent relative to each other. However, birefringent phase matching has beam walk-offs, and polarization correction is required to generate many harmonics so that the process is quite complicated. There would be phase fluctuations when the harmonics are split and then recombined during generation. Thus using birefringent phase matching will require elaborate phase locking and stabilization to maintain phase coherence among the harmonics [1]. Quasi-phase-matched (QPM) nonlinear mixing is another efficient approach to generating laser harmonics. Two-stage cascaded parametric generation and generation to the third harmonic in a single QPM crystal have been demonstrate

Generation of octave-spanning multiple harmonics for ultrafast waveform synthesis

Up to seven laser harmonics covering more than two octaves in frequency have been generated efficiently in a single PPLT crystal, permitting the synthesis of 1.5 femtosecond pulses in a stable and compact setting