Validation of nonlinear PCA

Linear principal component analysis (PCA) can be extended to a nonlinear PCA by using artificial neural networks. But the benefit of curved components requires a careful control of the model complexity. Moreover, standard techniques for model selection, including cross-validation and more generally the use of an independent test set, fail when applied to nonlinear PCA because of its inherent unsupervised characteristics. This paper presents a new approach for validating the complexity of nonlinear PCA models by using the error in missing data estimation as a criterion for model selection. It is motivated by the idea that only the model of optimal complexity is able to predict missing values with the highest accuracy. While standard test set validation usually favours over-fitted nonlinear PCA models, the proposed model validation approach correctly selects the optimal model complexity.Comment: 12 pages, 5 figure

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

The persistence of epiphyseal scars in the distal radius in adult individuals

The use of radiographic imaging in the estimation of chronological age facilitates the analysis of structures not visible on gross morphological inspection. Following the completion of epiphyseal fusion, a thin radio-opaque band, the epiphyseal scar, may be observed at the locus of the former growth plate. The obliteration of this feature has previously been interpreted as the final stage of skeletal maturation and consequently has been included as a criterion in several methods of age estimation, particularly from the distal radius. Due to the recommendations relating to age estimation in living individuals, accurate assessment of age from the distal radius is of great importance in human identification; however, the validity of the interpretation of the obliteration of the epiphyseal scar as an age-related process has not been tested. A study was undertaken to assess the persistence of epiphyseal scars in adults between 20 and 50 years of age through the assessment of 616 radiographs of left and right distal radii from a cross-sectional population. This study found that 86 % of females and 78 % of males retained some remnant of the epiphyseal scar in the distal radius. The relationships between chronological age, biological sex and the persistence of the epiphyseal scar were not statistically significant. The findings of this study indicate that the epiphyseal scars may persist in adult individuals until at least 50 years of age. No maximum age should therefore be applied to the persistence of an epiphyseal scar in the distal radius

Dynamic sea level changes following changes in the thermohaline circulation

Using the coupled climate model CLIMBER-3a, we investigate changes in sea surface elevation due to a weakening of the thermohaline circulation (THC). In addition to a global sea level rise due to a warming of the deep sea, this leads to a regional dynamic sea level change which follows quasi-instantaneously any change in the ocean circulation. We show that the magnitude of this dynamic effect can locally reach up to ~1m, depending on the initial THC strength. In some regions the rate of change can be up to 20-25 mm/yr. The emerging patterns are discussed with respect to the oceanic circulation changes. Most prominent is a south-north gradient reflecting the changes in geostrophic surface currents. Our results suggest that an analysis of observed sea level change patterns could be useful for monitoring the THC strength.Comment: Climate Dynamics (2004), submitted. See also http://www.pik-potsdam.de/~ander

Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-kB Activity

The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis.Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment.NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis

Microfluidic Chip for Molecular Amplification of Influenza A RNA in Human Respiratory Specimens

A rapid, low cost, accurate point-of-care (POC) device to detect influenza virus is needed for effective treatment and control of both seasonal and pandemic strains. We developed a single-use microfluidic chip that integrates solid phase extraction (SPE) and molecular amplification via a reverse transcription polymerase chain reaction (RT-PCR) to amplify influenza virus type A RNA. We demonstrated the ability of the chip to amplify influenza A RNA in human nasopharyngeal aspirate (NPA) and nasopharyngeal swab (NPS) specimens collected at two clinical sites from 2008–2010. The microfluidic test was dramatically more sensitive than two currently used rapid immunoassays and had high specificity that was essentially equivalent to the rapid assays and direct fluorescent antigen (DFA) testing. We report 96% (CI 89%,99%) sensitivity and 100% (CI 95%,100%) specificity compared to conventional (bench top) RT-PCR based on the testing of n = 146 specimens (positive predictive value = 100%(CI 94%,100%) and negative predictive value = 96%(CI 88%,98%)). These results compare well with DFA performed on samples taken during the same time period (98% (CI 91%,100%) sensitivity and 96%(CI 86%,99%) specificity compared to our gold standard testing). Rapid immunoassay tests on samples taken during the enrollment period were less reliable (49%(CI 38%,61%) sensitivity and 98%(CI 98%,100%) specificity). The microfluidic test extracted and amplified influenza A RNA directly from clinical specimens with viral loads down to 103 copies/ml in 3 h or less. The new test represents a major improvement over viral culture in terms of turn around time, over rapid immunoassay tests in terms of sensitivity, and over bench top RT-PCR and DFA in terms of ease of use and portability

The Relationship between Oral Squamous Cell Carcinoma and Human Papillomavirus: A Meta-Analysis of a Chinese Population (1994–2011)

Background: Previous studies indicated that oral squamous cell carcinomas (OSCC) might be related to human papilloma virus (HPV) infection. However, up to now, there still lacks a large sample study to analyze the relationship between OSCC in a Chinese population and oral HPV infection. In the present study, we used a meta-analysis to evaluate the relationship of OSCC with HPV infection in a Chinese population. Methods: The reports on HPV and OSCC in a Chinese population published between January, 1994, and September, 2011 were retrieved via CNKI/WANFANG/OVID/MEDLINE databases. According to the inclusion criteria, we selected 18 eligible case-control studies. After testing the heterogeneity of the studies by the Cochran Q test, the meta-analyses for HPV and HPV16 were performed using the fixed effects model. Results: The overall positive rates of HPV and HPV16 in OSCC were 58.0 % (354/610; 95 % confidence interval [CI], 54.1–61.9) and 47.47 % (169/356; 95 % CI: 42.3–52.7), respectively; which were significantly higher than those in normal controls 10.44% (26/249; 95 % CI: 7.2–14.7) and 7.1 % (13/182; 95 % CI: 4.2–11.8). Quantitative meta-analysis revealed that, compared with normal controls, the combined odds ratios of OSCC with HPV or HPV16 infection were 12.7 (95 % CI: 8.0–20.0) and 9.0 (95% CI: 5.1–15.6), respectively. Both Begg’s test and funnel plots revealed that no publication bias was found in this present study (P.0.05)

XPD codon 312 and 751 polymorphisms, and AFB1 exposure, and hepatocellular carcinoma risk

<p>Abstract</p> <p>Background</p> <p>Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of hepatocellular carcinoma (HCC) related to the exposure of aflatoxin B1 (AFB1). In this study, we have focused on the polymorphisms of xeroderma pigmentosum complementation group D (XPD) codon 312 and 751 (namely Asp312Asn and Lys751Gln), involved in nucleotide excision repair.</p> <p>Methods</p> <p>We conducted a case-control study including 618 HCC cases and 712 controls to evaluate the associations between these two polymorphisms and HCC risk for Guangxi population by means of TaqMan-PCR and PCR-RFLP analysis.</p> <p>Results</p> <p>We found that individuals featuring the XPD genotypes with codon 751 Gln alleles (namely XPD-LG or XPD-GG) were related to an elevated risk of HCC compared to those with the homozygote of XPD codon 751 Lys alleles [namely XPD-LL, adjusted odds ratios (ORs) were 1.75 and 2.47; 95% confidence interval (CIs) were 1.30-2.37 and 1.62-3.76, respectively]. A gender-specific role was evident that showed an higher risk for women (adjusted OR was 8.58 for XPD-GG) than for men (adjusted OR = 2.90 for XPD-GG). Interestingly, the interactive effects of this polymorphism and AFB1-exposure information showed the codon 751 Gln alleles increase the risk of HCC for individuals facing longer exposure years (<it>P</it>_interaction= 0.011, OR = 0.85). For example, long-exposure-years (> 48 years) individuals who carried XDP-GG had an adjusted OR of 470.25, whereas long-exposure-years people with XDP-LL were at lower risk (adjusted OR = 149.12). However, we did not find that XPD codon 312 polymorphism was significantly associated with HCC risk.</p> <p>Conclusion</p> <p>These findings suggest that XPD Lys751Gln polymorphism is an important modulator of AFB1 related-HCC development in Guangxi population.</p

Distinguishing four components underlying physical activity: a new approach to using physical activity questionnaire data in old age

<p>Abstract</p> <p>Background</p> <p>It is evident that physical activity has many benefits, but it often remains unclear which types of activity are optimal for health and functioning in old age. The aim of this methodological study was to propose a method for distinguishing four components underlying self reported physical activity of older adults: intensity, muscle strength, turning actions and mechanical strain.</p> <p>Methods</p> <p>Physical activity was assessed by the validated LAPAQ questionnaire among 1699 older adults of the Longitudinal Aging Study Amsterdam. Based on expert consultation and literature review, the four component scores for several individual daily and sports activities were developed. Factor analysis was performed to confirm whether the developed components indeed measured different constructs of physical activity.</p> <p>Results</p> <p>Based on the factor analyses, three components were distinguished: 1. intensity and muscle strength loaded on the same factor, 2. mechanical strain and 3. turning actions. Analyses in gender, age and activity level subgroups consistently distinguished three factors.</p> <p>Conclusion</p> <p>Future research using these components may contribute to our understanding of how specific daily and sports activities may have a different influence on health and physical functioning in old age.</p