Radiative rates for E1, E2, M1, and M2 transitions in F-like ions with 37≤Z≤53

Calculations of energy levels, radiative rates and lifetimes are reported for 17 F-like ions with 37≤Z≤53. For brevity, results are only presented among the lowest 113 levels of the 2s²2p⁵, 2s2p⁶, 2s²2p⁴3ℓ, 2s2p⁵3ℓ, and 2p⁶3ℓ configurations, although the calculations have been performed for up to 501 levels in each ion. The general-purpose relativistic atomic structure package (grasp) has been adopted for the calculations, and radiative rates (along with oscillator strengths and line strengths) are listed for all E1, E2, M1, and M2 transitions of the ions. Comparisons are made with earlier available experimental and theoretical energies, although these are limited to only a few levels for most ions. Therefore for additional accuracy assessments, particularly for energy levels, analogous calculations have been performed with the Flexible Atomic Code (fac), for up to 72 259 levels. Limited previous results are available for radiative rates for comparison purposes, and no large discrepancy is observed for any transition and/or ion.

Influence of the cutting edge micro-geometry of PCBN tools on the flank wear in orthogonal quenched and tempered turning M2 steel

Quenched and tempered high-speed steels obtained by powder metallurgy are commonly used in automotive components, such as valve seats of combustion engines. In order to machine these components, tools with high wear resistance and appropriate cutting edge geometry are required. This work aims to investigate the influence of the edge preparation of polycrystalline cubic boron nitride (PCBN) tools on the wear behavior in the orthogonal longitudinal turning of quenched and tempered M2 high-speed steels obtained by powder metallurgy. For this research, PCBN tools with high and low-CBN content have been used. Two different cutting edge geometries with a honed radius were tested: with a ground land (S shape) and without it (E shape). Also, the cutting speed was varied from 100 to 220 m/min. A rigid CNC lathe was used. The results showed that the high-CBN, E-shaped tool presented the longest life for a cutting speed of 100 m/min. High-CBN tools with a ground land and honed edge radius (S shaped) showed edge damage and lower values of the tool’s life. Low-CBN, S-shaped tools showed similar results, but with an inferior performance when compared with tools with high CBN content in both forms of edge preparation.

Macrophages and CD4 T-cells in rheumatoid arthritis and their modulation by JAK inhibitors

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that causes significant morbidity and mortality and has no cure. Although early treatment strategies and biologic therapies such as TNFα blocking antibodies have revolutionised treatment, there still remains considerable unmet need. JAK kinase inhibitors, which target multiple inflammatory cytokines, have shown efficacy in treating RA although their exact mechanism of action remains to be determined. Stratified medicine promises to deliver the right drug to the right patient at the right time by using predictive ‘omic biomarkers discovered using bioinformatic and “Big Data” techniques. Therefore, knowledge across the realms of clinical rheumatology, applied immunology, bioinformatics and data science is required to realise this goal. Aim: To use bioinformatic tools to analyse the transcriptome of CD14 macrophages derived from patients with inflammatory arthritis and define a JAK/STAT signature. Thereafter to investigate the role of JAK inhibition on inflammatory cytokine production in a macrophage cell contact activation assay. Finally, to investigate JAK inhibition, following RA synovial fluid stimulation of monocytes. Methods and Results: Using bioinformatic software such as limma from the Bioconductor repository, I determined that there was a JAK/STAT signature in synovial CD14 macrophages from patients with RA and this differed from psoriatic arthritis samples. JAK inhibition using a JAK1/3 inhibitor tofacitinib reduced TNFα production when macrophages were cell contact activated by cytokine stimulated CD4 T-cells. Other pro-inflammatory cytokines such as IL-6 and chemokines such as IP-10 were also reduced. RA synovial fluid failed to stimulate monocytes to phosphorylate STAT1, 3 or 6 but CD4 T-cells activated STAT3 with this stimulus. RNA sequencing of synovial fluid stimulated CD4 T-cells showed an upregulation of SOCS3, BCL6 and SBNO2, a gene associated with RA but with unknown function and tofacitinib reversed this. Conclusion: These studies demonstrate that tofacitinib is effective at reducing inflammatory mediator production in a macrophage cell contact assay and also affects soluble factor mediated stimulation of CD4 T-cells. This suggests that the effectiveness of JAK inhibition is due to inhibition of multiple cytokine pathways such as IL-6, IL-15 and interferon. RNA sequencing is a useful tool to identify non-coding RNA transcripts that are associated with synovial fluid stimulation and JAK inhibition but these require further validation. SBNO2, a gene that is associated with RA, may be biomarker of tofacitinib treatment but requires further investigation and validation in wider disease cohorts.

IL-34- and M-CSF-induced macrophages switch memory T cells into Th17 cells via membrane IL-1α: Immunomodulation

International audience

HIV-1 Mutation and Recombination Rates Are Different in Macrophages and T-cells

High rates of mutation and recombination help human immunodeficiency virus (HIV) to evade the immune system and develop resistance to antiretroviral therapy. Macrophages and T-cells are the natural target cells of HIV-1 infection. A consensus has not been reached as to whether HIV replication results in differential recombination between primary T-cells and macrophages. Here, we used HIV with silent mutation markers along with next generation sequencing to compare the mutation and the recombination rates of HIV directly in T lymphocytes and macrophages. We observed a more than four-fold higher recombination rate of HIV in macrophages compared to T-cells (p < 0.001) and demonstrated that this difference is not due to different reliance on C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 5 (CCR5) co-receptors between T-cells and macrophages. We also found that the pattern of recombination across the HIV genome (hot and cold spots) remains constant between T-cells and macrophages despite a three-fold increase in the overall recombination rate. This indicates that the difference in rates is a general feature of HIV DNA synthesis during macrophage infection. In contrast to HIV recombination, we found that T-cells have a 30% higher mutation rate than macrophages (p < 0.001) and that the mutational profile is similar between these cell types. Unexpectedly, we found no association between mutation and recombination in macrophages, in contrast to T-cells. Our data highlights some of the fundamental difference of HIV recombination and mutation amongst these two major target cells of infection. Understanding these differences will provide invaluable insights toward HIV evolution and how the virus evades immune surveillance and anti-retroviral therapeutics.

Candida albicans Modifies the Protein Composition and Size Distribution of THP1 macrophages-derived Extracellular Vesicles.

The effectiveness of macrophages in the response to systemic candidiasis is crucial to an effective clearance of the pathogen. The secretion of proteins, mRNAs, non-coding RNAs and lipids through extracellular vesicles (EVs) is one of the mechanisms of communication between immune cells. EVs change their cargo to mediate different responses, and may play a role in the response against infections. Thus, we have undertaken the first quantitative proteomic analysis on the protein composition of THP1 macrophages-derived EVs during the interaction with Candida albicans. This study revealed changes in EVs sizes and in protein composition, and allowed the identification and quantification of 717 proteins. Of them, 133 proteins changed their abundance due to the interaction. The differentially abundant proteins were involved in functions relating to immune response, signaling, or cytoskeletal reorganization. THP1-derived EVs, both from control and from Candida-infected macrophages, had similar effector functions on other THP1-differenciated macrophages, activating ERK and p38 kinases, and increasing both the secretion of proinflammatory cytokines and the candidacidal activity; while in THP1 non-differenciated monocytes, only EVs from infected macrophages increased significantly the TNF-α secretion. Our findings provide new information on the role of macrophage-derived EVs in response to C. albicans infection and in macrophages communication.

What lies beneath? : The pattern and abundance of the subterranean tuber bank of the invasive liana cat’s claw creeper, Macfadyena unguis-cati (Bignoniaceae)

Cat’s claw creeper, Macfadyena unguis-cati (L.) Gentry (Bignoniaceae) is a major environmental weed of riparian areas, rainforest communities and remnant natural vegetation in coastal Queensland and New South Wales, Australia. In densely infested areas, it smothers standing vegetation, including large trees, and causes canopy collapse. Quantitative data on the ecology of this invasive vine are generally lacking. The present study examines the underground tuber traits of M. unguis-cati and explores their links with aboveground parameters at five infested sites spanning both riparian and inland vegetation. Tubers were abundant in terms of density (~1000 per m2), although small in size and low in level of interconnectivity. M. unguis-cati also exhibits multiple stems per plant. Of all traits screened, the link between stand (stem density) and tuber density was the most significant and yielded a promising bivariate relationship for the purposes of estimation, prediction and management of what lies beneath the soil surface of a given M. unguis-cati infestation site. The study also suggests that new recruitment is primarily from seeds, not from vegetative propagation as previously thought. The results highlight the need for future biological-control efforts to focus on introducing specialist seed- and pod-feeding insects to reduce seed-output.

Ethnic differences in body composition and anthropometric characteristics in Australian Caucasian and urban Indigenous children

The objective was to compare ethnic differences in anthropometry, including size, proportions and fat distribution, and body composition in a cohort of seventy Caucasian (forty-four boys, twenty-six girls) and seventy-four urban Indigenous (thirty-six boys, thirty-eight girls) children (aged 9–15 years). Anthropometric measures (stature, body mass, eight skinfolds, thirteen girths, six bone lengths and five bone breadths) and body composition assessment using dual-energy X-ray absorptiometry were conducted. Body composition variables including total body fat percentage and percentage abdominal fat were determined and together with anthropometric indices, including BMI (kg/m2), abdominal:height ratio (AHtR) and sum of skinfolds, ethnic differences were compared for each sex. After adjustment for age, Indigenous girls showed significantly (P < 0·05) greater trunk circumferences and proportion of overweight and obesity than their Caucasian counterparts. In addition, Indigenous children had a significantly greater proportion (P < 0·05) of trunk fat. The best model for total and android fat prediction included sum of skinfolds and age in both sexes (>93 % of variation). Ethnicity was only important in girls where abdominal circumference and AHtR were included and Indigenous girls showed significantly (P < 0·05) smaller total/android fat deposition than Caucasian girls at the given abdominal circumference or AHtR values. Differences in anthropometric and fat distribution patterns in Caucasian and Indigenous children may justify the need for more appropriate screening criteria for obesity in Australian children relevant to ethnic origin.

Beneficial effects of exercise : shifting the focus from body weight to other markers of health

Background: Exercise is widely promoted as a method of weight management, while the other health benefits are often ignored. The purpose of this study was to examine whether exercise-induced improvements in health are influenced by changes in body weight. Methods: Fifty-eight sedentary overweight/obese men and women (BMI 31.8 (SD 4.5) kg/m2) participated in a 12-week supervised aerobic exercise intervention (70% heart rate max, five times a week, 500 kcal per session). Body composition, anthropometric parameters, aerobic capacity, blood pressure and acute psychological response to exercise were measured at weeks 0 and 12. Results: The mean reduction in body weight was −3.3 (3.63) kg (p<0.01). However, 26 of the 58 participants failed to attain the predicted weight loss estimated from individuals’ exercise-induced energy expenditure. Their mean weight loss was only −0.9 (1.8) kg (p<0.01). Despite attaining a lower-than-predicted weight reduction, these individuals experienced significant increases in aerobic capacity (6.3 (6.0) ml/kg/min; p<0.01), and a decreased systolic (−6.00 (11.5) mm Hg; p<0.05) and diastolic blood pressure (−3.9 (5.8) mm Hg; p<0.01), waist circumference (−3.7 (2.7) cm; p<0.01) and resting heart rate (−4.8 (8.9) bpm, p<0.001). In addition, these individuals experienced an acute exercise-induced increase in positive mood. Conclusions: These data demonstrate that significant and meaningful health benefits can be achieved even in the presence of lower-than-expected exercise-induced weight loss. A less successful reduction in body weight does not undermine the beneficial effects of aerobic exercise. From a public health perspective, exercise should be encouraged and the emphasis on weight loss reduced.

Exercise alone is not enough : weight loss also needs a healthy (Mediterranean) diet?

Objective: In the majority of exercise intervention studies, the aggregate reported weight loss is often small. The efficacy of exercise as a weight loss tool remains in question. The aim of the present study was to investigate the variability in appetite and body weight when participants engaged in a supervised and monitored exercise programme. ---------- Design: Fifty-eight obese men and women (BMI = 31·8 ± 4·5 kg/m2) were prescribed exercise to expend approximately 2092 kJ (500 kcal) per session, five times a week at an intensity of 70 % maximum heart rate for 12 weeks under supervised conditions in the research unit. Body weight and composition, total daily energy intake and various health markers were measured at weeks 0, 4, 8 and 12. ---------- Results: Mean reduction in body weight (3·2 ± 1·98 kg) was significant (P < 0·001); however, there was large individual variability (−14·7 to +2·7 kg). This large variability could be largely attributed to the differences in energy intake over the 12-week intervention. Those participants who failed to lose meaningful weight increased their food intake and reduced intake of fruits and vegetables. ---------- Conclusion: These data have demonstrated that even when exercise energy expenditure is high, a healthy diet is still required for weight loss to occur in many people.

Dual-process action of exercise on appetite control : increase in orexigenic drive but improvement in meal-induced satiety

Background: Exercise could contribute to weight loss by altering the sensitivity of the appetite regulatory system. Objective: The aim of this study was to assess the effects of 12 wk of mandatory exercise on appetite control. Design: Fifty-eight overweight and obese men and women [mean (±SD) body mass index (in kg/m2) = 31.8 ± 4.5, age = 39.6 ± 9.8 y, and maximal oxygen intake = 29.1 ± 5.7 mL · kg–1 · min–1] completed 12 wk of supervised exercise in the laboratory. The exercise sessions were designed to expend 2500 kcal/wk. Subjective appetite sensations and the satiating efficiency of a fixed breakfast were compared at baseline (week 0) and at week 12. An Electronic Appetite Rating System was used to measure subjective appetite sensations immediately before and after the fixed breakfast in the immediate postprandial period and across the whole day. The satiety quotient of the breakfast was determined by calculating the change in appetite scores relative to the breakfast's energy content. Results: Despite large variability, there was a significant reduction in mean body weight (3.2 ± 3.6 kg), fat mass (3.2 ± 2.2 kg), and waist circumference (5.0 ± 3.2 cm) after 12 wk. The analysis showed that a reduction in body weight and body composition was accompanied by an increase in fasting hunger and in average hunger across the day (P < 0.0001). Paradoxically, the immediate and delayed satiety quotient of the breakfast also increased significantly (P < 0.05). Conclusions: These data show that the effect of exercise on appetite regulation involves at least 2 processes: an increase in the overall (orexigenic) drive to eat and a concomitant increase in the satiating efficiency of a fixed meal.

Trends in demographic, health behaviour factors, and self-perceived weight status : influences on obesity in Australia from 1995 to 2005

Overweight and obesity are two of the most important emerging public health issues in our time and regarded by the World Health Organisation [WHO] (1998) as a worldwide epidemic. The prevalence of obesity in the USA is the highest in the world, and Australian obesity rates fall into second place. Currently, about 60% of Australian adults are overweight (BMI „d 25kg/m2). The socio-demographic factors associated with overweight and/or obesity have been well demonstrated, but many of the existing studies only examined these relationships at one point of time, and did not examine whether significant relationships changed over time. Furthermore, only limited previous research has examined the issue of the relationship between perception of weight status and actual weight status, as well as factors that may impact on people¡¦s perception of their body weight status. Aims: The aims of the proposed research are to analyse the discrepancy between perceptions of weight status and actual weight status in Australian adults; to examine if there are trends in perceptions of weight status in adults between 1995 to 2004/5; and to propose a range of health promotion strategies and furth er research that may be useful in managing physical activity, healthy diet, and weight reduction. Hypotheses: Four alternate hypotheses are examined by the research: (1) there are associations between independent variables (e.g. socio -demographic factors, physical activity and dietary habits) and overweight and/or obesity; (2) there are associations between the same independent variables and the perception of overweight; (3) there are associations between the same independent variables and the discrepancy between weight status and perception of weight status; and (4) there are trends in overweight and/or obesity, perception of overweight, and the discrepancy in Australian adults from 1995 to 2004/5. Conceptual Framework and Methods: A conceptual framework is developed that shows the associations identified among socio -demographic factors, physical activity and dietary habits with actual weight status, as well as examining perception of weight status. The three latest National Health Survey data bases (1995 , 2001 and 2004/5) were used as the primary data sources. A total of 74,114 Australian adults aged 20 years and over were recruited from these databases. Descriptive statistics, bivariate analyses (One -Way ANOVA tests, unpaired t-tests and Pearson chi-square tests), and multinomial logistic regression modelling were used to analyse the data. Findings: This research reveals that gender, main language spoken at home, occupation status, household structure, private health insurance status, and exercise are related to the discrepancy between actual weight status and perception of weight status, but only gender and exercise are related to the discrepancy across the three time point s. The current research provides more knowledge about perception of weight status independently. Factors which affect perception of overweight are gender, age, language spoken at home, private health insurance status, and diet ary habits. The study also finds that many factors that impact overweight and/or obesity also have an effect on perception of overweight, such as age, language spoken at home, household structure, and exercise. However, some factors (i.e. private health insurance status and milk consumption) only impact on perception of overweight. Furthermore, factors that are rel ated to people’s overweight are not totally related to people’s underestimation of their body weight status in the study results. Thus, there are unknown factors which can affect people’s underestimation of their body weight status. Conclusions: Health promotion and education activities should provide education about population health education and promotion and education for particular at risk sub -groups. Further research should take the form of a longitudinal study design ed to examine the causal relationship between overweight and/or obesity and underestimation of body weight status, it should also place more attention on the relationships between overweight and/or obesity and dietary habits, with a more comprehensive representation of SES. Moreover, further research that deals with identification of characteristics about perception of weight status, in particular the underestimation of body weight status should be undertaken.

Influence of UGT1A9 intronic I399C4T polymorphism on SN-38 glucuronidation in Asian cancer patients

Genetic polymorphisms in hepatically expressed UGT1A1 and UGT1A9 contribute to the interindividual variability i-n irinotecan disposition and toxicity. We screened UGT1A1 (UGT1A1*60, g.−3140G>A, UGT1A1*28 and UGT1A1*6) and UGT1A9 (g.−118(T)9>10 and I399C>T) genes for polymorphic variants in the promoter and coding regions, and the genotypic effect of UGT1A9 I399C>T polymorphism on irinotecan disposition in Asian cancer patients was investigated. Blood samples were collected from 45 patients after administration of irinotecan as a 90 min intravenous infusion of 375 mg/m2 once in every 3 weeks. Genotypic–phenotypic correlates showed that cancer patients heterozygous or homozygous for the I399C>T allele had approximately 2-fold lower systemic exposure to SN-38 (P<0.05) and a trend towards a higher relative extent of glucuronidation (REG) of SN-38 (P>0.05). UGT1A1–1A9 diplotype analysis showed that patients harbouring the H1/H2 (TG6GT10T/GG6GT9C) diplotype had 2.4-fold lower systemic exposure to SN-38 glucuronide (SN-38G) compared with patients harbouring the H1/H5 (TG6GT10T/GG6GT10C) diplotype (P=0.025). In conclusion, this in vivo study supports the in vitro findings of Girard et al. and suggests that the UGT1A9 I399C>T variant may be an important glucuronidating allele affecting the pharmacokinetics of SN-38 and SN-38G in Asian cancer patients receiving irinotecan chemotherapy.

PDMS spreading morphological patterns on substrates of different hydrophilicity in air vacuum and water

In paper has been to investigate the morphological patterns and kinetics of PDMS spreading on silicon wafer using combination of techniques like ellipsometry, atomic force microscope (AFM), scanning electron microscope (SEM) and optical microscopy. A macroscopic silicone oil drops as well as PDMS water based emulsions were studied after deposition on a flat surface of silicon wafer in air, water and vacuum. our own measurements using an imaging ellipsometer, which also clearly shows the presence of a precursor film. The diffusion constant of this film, measured with a 60 000 cS PDMS sample spreading on a hydrophilic silicon wafer, is Df = 1.4  10-11 m2/s. Regardless of their size, density and method of deposition, droplets on both types of wafer (hydrophilic and hydrophobic) flatten out over a period of many hours, up to 3 days. During this process neighbouring droplets may coalesce, but there is strong evidence that some of the PDMS from the droplets migrates into a thin, continuous film that covers the surface in between droplets. The thin film appears to be ubiquitous if there has been any deposition of PDMS. However, this statement needs further verification. One question is whether the film forms immediately after forced drying, or whether in some or all cases it only forms by spreading from isolated droplets as they slowly flatten out.

Latitude variation in pancreatic cancer mortality in Australia

Objectives: Ecological studies support the hypothesis that there is an association between vitamin D and pancreatic cancer (PaCa) mortality, but observational studies are somewhat conflicting. We sought to contribute further data to this issue by analyzing the differences in PaCa mortality across the eastern states of Australia and investigating if there is a role of vitamin D-effective ultraviolet radiation (DUVR), which is related to latitude. ---------- Methods: Mortality data from 1968 to 2005 were sourced from the Australian General Record of Incidence and Mortality books. Negative binomial models were fitted to calculate the association between state and PaCa mortality. Clear sky monthly DUVR in each capital city was also modeled. ---------- Results: Mortality from PaCa was 10% higher in southern states than in Queensland, with those in Victoria recording the highest mortality risk (relative risk, 1.13; 95% confidence interval, 1.09-1.17). We found a highly significant association between DUVR and PaCa mortality, with an estimated 1.5% decrease in the risk per 10-kJ/m2 increase in yearly DUVR. ---------- Conclusions: These data show an association between latitude, DUVR, and PaCa mortality. Although this study cannot be used to infer causality, it supports the need for further investigations of a possible role of vitamin D in PaCa etiology.