Lower bounds on the dilation of plane spanners

(I) We exhibit a set of 23 points in the plane that has dilation at least $1.4308$, improving the previously best lower bound of $1.4161$ for the worst-case dilation of plane spanners. (II) For every integer $n\geq13$, there exists an $n$-element point set $S$ such that the degree 3 dilation of $S$ denoted by $\delta_0(S,3) \text{ equals } 1+\sqrt{3}=2.7321\ldots$ in the domain of plane geometric spanners. In the same domain, we show that for every integer $n\geq6$, there exists a an $n$-element point set $S$ such that the degree 4 dilation of $S$ denoted by $\delta_0(S,4) \text{ equals } 1 + \sqrt{(5-\sqrt{5})/2}=2.1755\ldots$ The previous best lower bound of $1.4161$ holds for any degree. (III) For every integer $n\geq6$, there exists an $n$-element point set $S$ such that the stretch factor of the greedy triangulation of $S$ is at least $2.0268$.Comment: Revised definitions in the introduction; 23 pages, 15 figures; 2 table

Stable Mutated tau441 Transfected SH-SY5Y Cells as Screening Tool for Alzheimer’s Disease Drug Candidates

The role of hyperphosphorylation of the microtubule-associated protein tau in the pathological processes of several neurodegenerative diseases is becoming better understood. Consequently, development of new compounds capable of preventing tau hyperphosphorylation is an increasingly hot topic. For this reason, dependable in vitro and in vivo models that reflect tau hyperphosphorylation in human diseases are needed. In this study, we generated and validated an in vitro model appropriate to test potential curative and preventive compound effects on tau phosphorylation. For this purpose, a stably transfected SH-SY5Y cell line was constructed over-expressing mutant human tau441 (SH-SY5Y-TMHT441). Analyses of expression levels and tau phosphorylation status in untreated cells confirmed relevance to human diseases. Subsequently, the effect of different established kinase inhibitors on tau phosphorylation (e.g., residues Thr231, Thr181, and Ser396) was examined. It was shown with several methods including immunosorbent assays and mass spectrometry that the phosphorylation pattern of tau in SH-SY5Y-TMHT441 cells can be reliably modulated by these compounds, specifically targeting JNK, GSK-3, CDK1/5, and CK1. These four protein kinases are known to be involved in in vivo tau phosphorylation and are therefore authentic indicators for the suitability of this new cell culture model for tauopathies

IL-6 secretion in osteoarthritis patients is mediated by chondrocyte-synovial fibroblast cross-talk and is enhanced by obesity

Increasing evidence suggests that inflammation plays a central role in driving joint pathology in certain patients with osteoarthritis (OA). Since many patients with OA are obese and increased adiposity is associated with chronic inflammation, we investigated whether obese patients with hip OA exhibited differential pro-inflammatory cytokine signalling and peripheral and local lymphocyte populations, compared to normal weight hip OA patients. No differences in either peripheral blood or local lymphocyte populations were found between obese and normal-weight hip OA patients. However, synovial fibroblasts from obese OA patients were found to secrete greater amounts of the pro-inflammatory cytokine IL-6, compared to those from normal-weight patients (p < 0.05), which reflected the greater levels of IL-6 detected in the synovial fluid of the obese OA patients. Investigation into the inflammatory mechanism demonstrated that IL-6 secretion from synovial fibroblasts was induced by chondrocyte-derived IL-6. Furthermore, this IL-6 inflammatory response, mediated by chondrocyte-synovial fibroblast cross-talk, was enhanced by the obesity-related adipokine leptin. This study suggests that obesity enhances the cross-talk between chondrocytes and synovial fibroblasts via raised levels of the pro-inflammatory adipokine leptin, leading to greater production of IL-6 in OA patients

Influenza A Virus Induces an Immediate Cytotoxic Activity in All Major Subsets of Peripheral Blood Mononuclear Cells

A replication defective influenza A vaccine virus (delNS1 virus) was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells.Peripheral blood mononuclear cells (PBMCs), isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt) virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN) interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood.Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer

Systematic review of worldwide variations of the prevalence of wheezing symptoms in children

Background: Considerable variation in the prevalence of childhood asthma and its symptoms (wheezing) has been observed in previous studies and there is evidence that the prevalence has been increasing over time. Methods: We have systematically reviewed the reported prevalence and time trends of wheezing symptoms among children, worldwide and within the same country over time. All studies comprising more than 1000 persons and meeting certain other quality criteria published over a 16-year period, between January 1990 and December 2005, are reported and a comparison of ISAAC (International Study of Asthma and Allergies in Childhood) and non-ISAAC studies is made, in part as a way of expanding the power to examine time trends (the older studies tend to be non-ISAAC), but also to examine possible methodological differences between ISAAC and non-ISAAC questions. Results: A wide range of current prevalence of wheeze was observed between and within countries over time. The UK had the highest recorded prevalence of 32.2% in children aged 13–14 in 1994–5 and Ethiopia had the lowest prevalence, 1.7% in children aged 10–19 in 1996. All studies in Australia and the UK were compared using multiple logistic regression. ISAAC phase I and III studies reported significantly higher prevalence of current wheeze (OR = 1.638) compared with non-ISAAC studies, after adjusting for various other factors (country, survey year, age of child, parental vs child response to the survey). Australia showed a significantly higher prevalence of current wheezing (OR = 1.343) compared with the UK, there was a significant increase in the prevalence odds ratio per survey year (2.5% per year), a significant decrease per age of child (0.7% per year), and a significantly higher response in current wheezing if the response was self-completed by the child (OR = 1.290). These factors, when explored separately for ISAAC and non-ISAAC studies, showed very different results. In ISAAC studies, or non-ISAAC studies using ISAAC questions, there was a significant decrease in current wheezing prevalence over time (2.5% per year). In non-ISAAC studies, which tend to cover an earlier period, there was a significant increase (2.6% per year) in current wheezing prevalence over time. This is very likely to be a result of prevalence of wheezing increasing from the 1970s up to the early 1990s, but decreasing since then. Conclusion: The UK has the highest recorded prevalence of wheezing and Ethiopia the lowest. Prevalence of wheezing in Australia and the UK has increased from the 1970s up to the early 1990s, but decreased since then and ISAAC studies report significantly higher prevalences than non-ISAAC studies

Mental health (GHQ12; CES-D) and attitudes towards the value of work among inmates of a semi-open prison and the long-term unemployed in Luxembourg

Aim: To analyse the relationships between mental health and employment commitment among prisoners and the long-term unemployed (LTU) trying to return to work. Method: Fifty-two of 62 male inmates of a semi-open prison (Givenich Penitentiary Centre, the only such unit in Luxembourg), and 69 LTU registered at the Luxembourg Employment Administration completed a questionnaire exploring: 1) mental health (measured by means of scales GHQ12 and CES-D); 2) employment commitment; 3) availability of a support network, selfesteem, empowerment; and 4) socio-demographic characteristics. Results: Compared with LTU, inmates were younger, more had work experience (54.9% vs 26.1%), and more were educated to only a low level (71.1% vs 58.0%). The link between employment commitment and mental health in the LTU was the opposite of that seen among the prisoners: the more significant the perceived importance of employment, the worse the mental health (GHQ12 p = 0.003; CES-D p < 0.001) of the LTU; in contrast, among prisoners, the GHQ12 showed that the greater the perceived value of work, the lower the psychic distress (p = 0.012). Greater empowerment was associated with less depression in both populations. The education levels of people who did not reach the end of secondary school, whether inmates or LTU, were negatively linked with their mental equilibrium. Conclusion: The two groups clearly need professional support. Future research should further investigate the link between different forms of professional help and mental health. Randomized controlled trials could be carried out in both groups, with interventions to improve work commitment for prisoners and to help with getting a job for LTU. For those LTU who value employment but cannot find it, the best help may be psychological support

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

The influence of systemic inflammation, dietary intake and stage of disease on rate of weight loss in patients with gastro-oesophageal cancer

Although weight loss is often a dominant symptom in patients with upper gastrointestinal malignancy, there is a lack of objective evidence describing changes in nutritional status and potential associations between weight loss, food intake, markers of systemic inflammation and stage of disease in such patients. Two hundred and twenty patients diagnosed with gastric/oesophageal cancer were studied. Patients underwent nutritional assessment consisting of calculation of body mass index, measurement of weight loss, dysphagia scoring and estimation of dietary intake. Serum acute-phase protein concentrations were determined by enzyme-linked immunosorbent assay. In all, 182 (83%) patients had lost weight at diagnosis (median loss, 7% body weight). Weight loss was associated with poor performance status, advanced disease stage, dysphagia, reduced dietary intake and elevated serum C-reactive protein (CRP) concentrations. Multiple regression identified dietary intake (estimate of effect, 38%), serum CRP concentrations (estimate of effect, 34%) and stage of disease (estimate of effect, 28%) as independent variables in determining degree of weight loss. Mechanisms other than reduced dietary intake or mechanical obstruction by the tumour appear to be involved in the nutritional decline in patients with gastro-oesophageal malignancy. Recognition that systemic inflammation plays a role in nutritional depletion may inform the development of appropriate therapeutic strategies to ameliorate weight loss, making patients more tolerant of cancer-modifying treatments such as chemotherapy

Higher fungal diversity is correlated with lower CO2 emissions from dead wood in a natural forest

Wood decomposition releases almost as much CO2 to the atmosphere as does fossil-fuel combustion, so the factors regulating wood decomposition can affect global carbon cycling. We used metabarcoding to estimate the fungal species diversities of naturally colonized decomposing wood in subtropical China and, for the first time, compared them to concurrent measures of CO2 emissions. Wood hosting more diverse fungal communities emitted less CO2, with Shannon diversity explaining 26 to 44% of emissions variation. Community analysis supports a ‘pure diversity’ effect of fungi on decomposition rates and thus suggests that interference competition is an underlying mechanism. Our findings extend the results of published experiments using low-diversity, laboratory-inoculated wood to a high-diversity, natural system. We hypothesize that high levels of saprotrophic fungal biodiversity could be providing globally important ecosystem services by maintaining dead-wood habitats and by slowing the atmospheric contribution of CO2 from the world’s stock of decomposing wood. However, large-scale surveys and controlled experimental tests in natural settings will be needed to test this hypothesis