Novel non-linear elastic structural analysis with generalised transverse element loads using a refined finite element

In the finite element modelling of structural frames, external loads such as wind loads, dead loads and imposed loads usually act along the elements rather than at the nodes only. Conventionally, when an element is subjected to these general transverse element loads, they are usually converted to nodal forces acting at the ends of the elements by either lumping or consistent load approaches. In addition, it is especially important for an element subjected to the first- and second-order elastic behaviour, to which the steel structure is critically prone to; in particular the thin-walled steel structures, when the stocky element section may be generally critical to the inelastic behaviour. In this sense, the accurate first- and second-order elastic displacement solutions of element load effect along an element is vitally crucial, but cannot be simulated using neither numerical nodal nor consistent load methods alone, as long as no equilibrium condition is enforced in the finite element formulation, which can inevitably impair the structural safety of the steel structure particularly. It can be therefore regarded as a unique element load method to account for the element load nonlinearly. If accurate displacement solution is targeted for simulating the first- and second-order elastic behaviour on an element on the basis of sophisticated non-linear element stiffness formulation, the numerous prescribed stiffness matrices must indispensably be used for the plethora of specific transverse element loading patterns encountered. In order to circumvent this shortcoming, the present paper proposes a numerical technique to include the transverse element loading in the non-linear stiffness formulation without numerous prescribed stiffness matrices, and which is able to predict structural responses involving the effect of first-order element loads as well as the second-order coupling effect between the transverse load and axial force in the element. This paper shows that the principle of superposition can be applied to derive the generalized stiffness formulation for element load effect, so that the form of the stiffness matrix remains unchanged with respect to the specific loading patterns, but with only the magnitude of the loading (element load coefficients) being needed to be adjusted in the stiffness formulation, and subsequently the non-linear effect on element loadings can be commensurate by updating the magnitude of element load coefficients through the non-linear solution procedures. In principle, the element loading distribution is converted into a single loading magnitude at mid-span in order to provide the initial perturbation for triggering the member bowing effect due to its transverse element loads. This approach in turn sacrifices the effect of element loading distribution except at mid-span. Therefore, it can be foreseen that the load-deflection behaviour may not be as accurate as those at mid-span, but its discrepancy is still trivial as proved. This novelty allows for a very useful generalised stiffness formulation for a single higher-order element with arbitrary transverse loading patterns to be formulated. Moreover, another significance of this paper is placed on shifting the nodal response (system analysis) to both nodal and element response (sophisticated element formulation). For the conventional finite element method, such as the cubic element, all accurate solutions can be only found at node. It means no accurate and reliable structural safety can be ensured within an element, and as a result, it hinders the engineering applications. The results of the paper are verified using analytical stability function studies, as well as with numerical results reported by independent researchers on several simple frames.

Online alcohol interventions : a systematic review

Background: There has been a significant increase in the availability of online programs for alcohol problems. A systematic review of the research evidence underpinning these programs is timely. Objectives: Our objective was to review the efficacy of online interventions for alcohol misuse. Systematic searches of Medline, PsycINFO, Web of Science, and Scopus were conducted for English abstracts (excluding dissertations) published from 1998 onward. Search terms were: (1) Internet, Web*; (2) online, computer*; (3) alcohol*; and (4) E\effect*, trial*, random* (where * denotes a wildcard). Forward and backward searches from identified papers were also conducted. Articles were included if (1) the primary intervention was delivered and accessed via the Internet, (2) the intervention focused on moderating or stopping alcohol consumption, and (3) the study was a randomized controlled trial of an alcohol-related screen, assessment, or intervention. Results: The literature search initially yielded 31 randomized controlled trials (RCTs), 17 of which met inclusion criteria. Of these 17 studies, 12 (70.6%) were conducted with university students, and 11 (64.7%) specifically focused on at-risk, heavy, or binge drinkers. Sample sizes ranged from 40 to 3216 (median 261), with 12 (70.6%) studies predominantly involving brief personalized feedback interventions. Using published data, effect sizes could be extracted from 8 of the 17 studies. In relation to alcohol units per week or month and based on 5 RCTs where a measure of alcohol units per week or month could be extracted, differential effect sizes to post treatment ranged from 0.02 to 0.81 (mean 0.42, median 0.54). Pre-post effect sizes for brief personalized feedback interventions ranged from 0.02 to 0.81, and in 2 multi-session modularized interventions, a pre-post effect size of 0.56 was obtained in both. Pre-post differential effect sizes for peak blood alcohol concentrations (BAC) ranged from 0.22 to 0.88, with a mean effect size of 0.66. Conclusions: The available evidence suggests that users can benefit from online alcohol interventions and that this approach could be particularly useful for groups less likely to access traditional alcohol-related services, such as women, young people, and at-risk users. However, caution should be exercised given the limited number of studies allowing extraction of effect sizes, the heterogeneity of outcome measures and follow-up periods, and the large proportion of student-based studies. More extensive RCTs in community samples are required to better understand the efficacy of specific online alcohol approaches, program dosage, the additive effect of telephone or face-to-face interventions, and effective strategies for their dissemination and marketing.

Investigation of phenol degradation : True reaction kinetics on fixed film titanium dioxide photocatalyst

This study of photocatalytic oxidation of phenol over titanium dioxide films presents a method for the evaluation of true reaction kinetics. A flat plate reactor was designed for the specific purpose of investigating the influence of various reaction parameters, specifically photocatalytic film thickness, solution flow rate (1–8 l min−1), phenol concentration (20, 40 and 80 ppm), and irradiation intensity (70.6, 57.9, 37.1and 20.4 W m−2), in order to further understand their impact on the reaction kinetics. Special attention was given to the mass transfer phenomena and the influence of film thickness. The kinetics of phenol degradation were investigated with different irradiation levels and initial pollutant concentration. Photocatalytic degradation experiments were performed to evaluate the influence of mass transfer on the reaction and, in addition, the benzoic acid method was applied for the evaluation of mass transfer coefficient. For this study the reactor was modelled as a batch-recycle reactor. A system of equations that accounts for irradiation, mass transfer and reaction rate was developed to describe the photocatalytic process, to fit the experimental data and to obtain kinetic parameters. The rate of phenol photocatalytic oxidation was described by a Langmuir–Hinshelwood type law that included competitive adsorption and degradation of phenol and its by-products. The by-products were modelled through their additive effect on the solution total organic carbon.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [?75 mmol/kg dry wt (dw)] and increased by a similar amount (?80%) after 1 h of recovery (133 ± 37.8 vs. 149 ± 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 ± 69 vs. 234 ± 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 ± 18.5 vs. 38.0 ± 7.7 mmol·kg dw-1·h-1, P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 ± 11 ?M (P < 0.001) and at the end of the recovery reached 77 ± 11 ?M (P < 0.001) with Caff. Phosphorylation of CaMKThr286 was similar after exercise and after 1 h of recovery, but after 4 h CaMKThr286 phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)Thr172 and AktSer473 was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.

Changes of mortality and causes of death from 1970 to 2005 and decomposition analysis in Shandong province [山东省1970-2005年人群死亡率极死因变化与差别分解分析]

Objective To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005,and to quantitatively estimate the influential factors. Methods Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors for the change of mortality. Results The total mortality had had a slight change since 1970s,but had increased since 1990s.However,both the mortality rates of age-adjusted and age-specific decreased significantly. The mortality of Group Ⅰ diseases including infectious diseases as well maternal and perinatal diseases decreased drastically. By contrast, the mortality of non-communicable chronic diseases (NCDs)including cardiovascular diseases(CVDs),cancer and injuries increased. The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely. Non-demographic factors were responsible for the decrease of Group Ⅰ disease and the increase of injuries. With respect to the increase of NCDs as a whole. Demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality. Nevertheless, for the increase of some leading NCD diseases as CVDs and cancer, the increase was mainly due to non-demographic rather than demographic factors. Conclusion Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect, the overall mortality in Shandong would maintain a balance or slightly rise in the coming years. Group Ⅰ diseases in Shandong had been effectively under control. Strategies focusing on disease control and prevention should be transferred to chronic diseases, especially leading NCDs, such as CVDs and cancer.

Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.

Functional evaluation of genetic variants associated with endometriosis near GREB1

STUDY QUESTION: Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? SUMMARY ANSWER: We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosis patients with defined genotypes. WHAT IS ALREADY KNOWN: Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype. STUDY DESIGN, SIZE, DURATION: Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. MAIN RESULTS AND THE ROLE OF CHANCE: Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. LIMITATIONS, REASONS FOR CAUTION: In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. WIDER IMPLICATIONS OF THE FINDINGS: This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology. STUDY FUNDING/COMPETING INTERESTS: Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests.

Genetic and environmental influences on migraine: a twin study across six countries

Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine.

Marker selection by Akaike information criterion and Bayesian information criterion

We carried out a discriminant analysis with identity by descent (IBD) at each marker as inputs, and the sib pair type (affected-affected versus affected-unaffected) as the output. Using simple logistic regression for this discriminant analysis, we illustrate the importance of comparing models with different number of parameters. Such model comparisons are best carried out using either the Akaike information criterion (AIC) or the Bayesian information criterion (BIC). When AIC (or BIC) stepwise variable selection was applied to the German Asthma data set, a group of markers were selected which provide the best fit to the data (assuming an additive effect). Interestingly, these 25-26 markers were not identical to those with the highest (in magnitude) single-locus lod scores.

An indication that non-informative vision eliminates the Kinaesthetic Fusion Effect

This study investigated the Kinaesthetic Fusion Effect (KFE) first described by Craske and Kenny in 1981. The current study did not replicate these findings. Participants did not perceive any reduction in the sagittal separation of a button pressed by the index finger of one arm and a probe touching the other, following repeated exposure to the tactile stimuli present on both unseen arms. This study’s failure to replicate the widely-cited KFE as described by Craske et al. (1984) suggests that it may be contingent on several aspects of visual information, especially the availability of a specific visual reference, the role of instructions regarding gaze direction, and the potential use of a line of sight strategy when referring felt positions to an interposed surface. In addition, a foreshortening effect was found; this may result from a line-of-sight judgment and represent a feature of the reporting method used. The transformed line of sight data were regressed against the participant reported values, resulting in a slope of 1.14 (right arm) and 1.11 (left arm), and r > 0.997 for each. The study also provides additional evidence that mis-perceptions of the mediolateral position of the limbs specifically their separation and consistent with notions of Gestalt grouping, is somewhat labile and can be influenced by active motions causing touch of one limb by the other. Finally, this research will benefit future studies that require participants to report the perceived locations of the unseen limbs.

The effect of emotional and attentional load on attentional startle modulation

The interactive effects of emotion and attention on attentional startle modulation were investigated in two experiments. Participants performed a discrimination and counting task with two visual stimuli during which acoustic eyeblink startle-eliciting probes were presented at long lead intervals. In Experiment 1, this task was combined with aversive Pavlovian conditioning. In Group Attend CS+, the attended stimulus was followed by an aversive unconditional stimulus (US) and the ignored stimulus was presented alone whereas the ignored stimulus was paired with the US in Group Attend CS−. In Experiment 2, a non-aversive reaction time task US replaced the aversive US. Regardless of the conditioning manipulation and consistent with a modality non-specific account of attentional startle modulation, startle magnitude was larger during attended than ignored stimuli in both experiments. Blink latency shortening was differentially affected by the conditioning manipulations suggesting additive effects of conditioning and discrimination and counting task on blink startle.

The effect of hexagonal boron nitride additive on the effectiveness of grease-based lubrication of a steel surface

Purpose: The purpose of this paper is to study the sliding and the vibrating fretting tests mechanism of h-BN micro-particles when used as a lubricating grease-2 additive. Design/methodology/approach: The fretting tests were conducted on steel/steel contacts using both vibrating fretting apparatus and the shaftsleeve slide fitted tester. The wear scars were characterized with profilometry. The tribological properties of grease-2 compounded with h-BN additive were also compared to those obtained for the commercial product Militec-4. Findings: The experiment showed significant differences between the results obtained from the vibrating fretting and the shaft-sleeve sliding fitted tests. Adding h-BN to the lubricant leads to a better performance in the shaft-sleeve slide regime than in the steel/steel vibrating test condition. Originality/value: The results of the experimental studies demonstrate the potential of h-BN as an additive for preventing fretting sliding, and can very useful for further application of compound grease-2 with h-BN additive in industrial equipment.