Thermally assisted ion beam etching of polytetrafluoroethylene, a new technique for high aspect ratio etching of MEMS

In micromechanics, the etching of high aspect ratio structures in polymers is a prime technology. Normally, oxygen-based reactive ion etching or the LIGA technique are used to achieve this goal. This paper reintroduces a different idea to create deep trenches at high etch speed: the ion beam etching of Teflon. Because of its extraordinary properties the etch selectivity with respect to most other materials is over 1000. A model is proposed to explain the high etch rate and selectivity. Generally, the etching ions are highly energetic and material from different sources is sputtered on top of the sample. The high selectivity, high anisotropy, and sputtering of material are thought to be responsible for the forming of micrograss during etching a sample. Ways are given to decrease or increase this grass. The high potential of this technique will be discussed and applications will be shown. Especially, the use of etched Teflon for direct moulding is believed to become the main use of this techniqu

Bayesian Meta-Analysis of Multiple Treatment Comparisons: An Introduction to Mixed Treatment Comparisons

AbstractRecently, mixed treatment comparisons (MTC) have been presented as an extension of traditional meta-analysis by including multiple different pairwise comparisons across a range of different interventions. MTC allow for indirect comparisons and can therefore provide very useful information for clinical and reimbursement decision-making in the absence of head-to-head data. In this article, we provide an introductory overview of MTC illustrated with example analyses of different drug treatments in rheumatoid arthritis using a continuous patient-reported end point. As a background, we start with an overview of the traditional meta-analyses for pairwise trials, and the difference between a traditional approach and a Bayesian approach. Next, the Bayesian MTC for continuous outcomes are presented. We finish with a discussion of how MTC can best be presented in order to maximize acceptance by target audiences, i.e., clinicians and market access decision-makers

Growth of the salt-tolerant yeast Zygosaccharomyces rouxii in microtiter plates:effects of NaCl, pH and temperature on growth and fusel alcohol production from branched-chain amino acids

Zygosaccharomyces rouxii, a salt-tolerant yeast isolated from the soy sauce process, produces fusel alcohols (isoamyl alcohol, active amyl alcohol and isobutyl alcohol) from branched-chain amino acids (leucine, isoleucine and valine, respectively) via the Ehrlich pathway. Using a high-throughput screening approach in microtiter plates, we have studied the effects of pH, temperature and salt concentration on growth of Z. rouxii and formation of fusel alcohols from branched-chain amino acids. Application of minor variations in pH (range 3-7) and NaCl concentrations (range 0-20%) per microtiter plate well allowed a rapid and detailed evaluation of fermentation conditions for optimal growth and metabolite production. Conditions yielding the highest cell densities were not optimal for fusel alcohol production. Maximal fusel alcohol production occurred at low pH (3.0-4.0) and low NaCl concentrations (0-4%) at 25°C. At pH 4.0-6.0 and 0-18% NaCl, considerable amounts of α-keto acids, the deaminated products from the branched-chain amino acids, accumulated extracellularly. The highest cell densities were obtained in plates incubated at 30°C. The results obtained under various incubation conditions with (deep-well) microtiter plates were validated in Erlenmeyer shake-flask cultures.

Psychometric properties of questionnaires evaluating health-related quality of life and functional status in polytrauma patients with lower extremity injury

BACKGROUND: Long term disability is common among polytrauma patients. However, as yet little information exists on how to adequately measure functional status and health-related quality of life following polytrauma. AIMS: To establish the unidimensionality, internal consistency and validity of two health-related quality of life measures and one functional status questionnaire among polytrauma patients. METHODS: 186 Patients with severe polytrauma including lower extremity injury completed the Sickness Impact Profile-136 (SIP-136), the Medical Outcomes Study 36-Item Short Health Survey (SF-36) and the Groningen Activity Restriction Scale (GARS) 15 months after injury. Unidimensionality and internal consistency was assessed by principal components analysis and Cronbach's alpha (alpha). To test the construct validity of the questionnaires, predetermined hypotheses were tested. RESULTS: The unidimensionality and internal consistency of the GARS and the SF-36, but not the SIP-136 were supported. The construct validity of the SF-36, GARS and to a lesser extent the SIP-136 was confirmed. CONCLUSION: The SF-36 and the GARS appear to be preferable for use in polytrauma patients over the SIP-136

Fusarium wilt of banana, a recurring threat to global banana production

TR4 first emerged in Southeast Asia (Ploetz, 1990) and its current rapid spread was analysed by Ordóñez et al. (2015). Subsequent studies showed that the TR4 strain is extremely virulent towards many banana cultivars, including Cavendish cultivars grown in large-scale monoculture plantations for export markets and many banana varieties important for food security and domestic consumption. There are no readily available solutions to manage this disease. Moreover, this global threat connects export trade, strongly dependent on the susceptible Cavendish cultivars, to local production systems wherein a range of banana varieties contributing to food security are also impacted.This research topic aims to provide a platform for information exchange and knowledge sharing. The contributions demonstrate an active research community in search of effective control of FWB. Taken together, the papers provide an overview of our current understanding of the biology and epidemiology of TR4, its management and how integrated and innovative solutions are required and need to be embraced by all stakeholders in an effort to build a sustainable banana industry for the future

Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans

The life span of the nematode Caenorhabditis elegans is under control of sensory signals detected by the amphid neurons. In these neurons, C. elegans expresses at least 13 Galpha subunits and a Ggamma subunit, which are involved in the transduction and modulation of sensory signals. Here, we show that loss-of-function mutations in the Galpha subunits odr-3, gpa-1 and gpa-9, in the Ggamma subunit gpc-1 and the introduction of extra copies of the Galpha subunit gpa-11 extend the life span of C. elegans. Loss-of-function of odr-3 and extra copies of gpa-11 act synergistically and can together extend life span more than two-fold, indicating that sensory signals play an important role in regulating life span. We show that gpa-1, gpa-11, odr-3 and gpc-1 all signal via the daf-16 FOXO family transcription factor. In addition, odr-3 and gpa-11 might suppress life span extension partially independent of the insulin/IGF-1 like receptor homologue daf-2. Our results suggest that the previously unanticipated nociceptive ASH and/or ADL neurons regulate longevity. We expect that the implication of specific G proteins will eventually contribute to the identification of the sensory cues that determine the rate of aging in C. elegans

Development and validation of an alternative parameter for quantification of signals emitted by fluorescently labelled bacteria in microscopic images

In this study, an alternative parameter for quantifying the signals of fluorescently labelled bacteria (e.g. propidium iodide, Cyanine 3, etc.) in microscopic images was investigated. Three common parameters (mean grey value (MGV), mean grey value which is corrected for the background (MGVcwB) and the signal to background ratio (SBR) per bacterial cell) are used as reference parameters. As an alternative, the coefficient of variation (CV) is defined as the ratio of the logarithm of the standard deviation and the logarithm of the mean grey value of a bacterial cell in a microscopic image. The actual fluorescence value was safeguarded by measuring commercially available fluorescence latex microspheres at regular time intervals within our study. The precision and the correlation of the respective values of MGV, MGVcwB, SBR and CV taken from identical images were measured and subsequently normalized in order to enhance the inter-parameter comparability. The average precision of CV was the highest (89% +/- 14) with decreasing numbers for MGVcwB, SBR, and MGV (78% +/- 25, 71% +/- 32, and, 52% +/- 22, respectively). Changes in operational parameters, e.g., microscope settings, protocol steps, etc., yielded good results for the CV but less precise results for MGV, MGVcwB, and SBR in the analyses of identical images. In conclusion, using the alternative parameter CV, changes in the composition of microbial ecosystems may thus be investigated at the highest precision level

Mechanism of life-long maintenance of neuron identity despite molecular fluctuations.

Cell fate is maintained over long timescales, yet molecular fluctuations can lead to spontaneous loss of this differentiated state. Our simulations identified a possible mechanism that explains life-long maintenance of ASE neuron fate in Caenorhabditis elegans by the terminal selector transcription factor CHE-1. Here, fluctuations in CHE-1 level are buffered by the reservoir of CHE-1 bound at its target promoters, which ensures continued che-1 expression by preferentially binding the che-1 promoter. We provide experimental evidence for this mechanism by showing that che-1 expression was resilient to induced transient CHE-1 depletion, while both expression of CHE-1 targets and ASE function were lost. We identified a 130 bp che-1 promoter fragment responsible for this resilience, with deletion of a homeodomain binding site in this fragment causing stochastic loss of ASE identity long after its determination. Because network architectures that support this mechanism are highly conserved in cell differentiation, it may explain stable cell fate maintenance in many systems

Expression of mammalian GPCRs in C. elegans generates novel behavioural responses to human ligands

BACKGROUND: G-protein-coupled receptors (GPCRs) play a crucial role in many biological processes and represent a major class of drug targets. However, purification of GPCRs for biochemical study is difficult and current methods of studying receptor-ligand interactions involve in vitro systems. Caenorhabditis elegans is a soil-dwelling, bacteria-feeding nematode that uses GPCRs expressed in chemosensory neurons to detect bacteria and environmental compounds, making this an ideal system for studying in vivo GPCR-ligand interactions. We sought to test this by functionally expressing two medically important mammalian GPCRs, somatostatin receptor 2 (Sstr2) and chemokine receptor 5 (CCR5) in the gustatory neurons of C. elegans. RESULTS: Expression of Sstr2 and CCR5 in gustatory neurons allow C. elegans to specifically detect and respond to somatostatin and MIP-1α respectively in a robust avoidance assay. We demonstrate that mammalian heterologous GPCRs can signal via different endogenous G(α )subunits in C. elegans, depending on which cells it is expressed in. Furthermore, pre-exposure of GPCR transgenic animals to its ligand leads to receptor desensitisation and behavioural adaptation to subsequent ligand exposure, providing further evidence of integration of the mammalian GPCRs into the C. elegans sensory signalling machinery. In structure-function studies using a panel of somatostatin-14 analogues, we identified key residues involved in the interaction of somatostatin-14 with Sstr2. CONCLUSION: Our results illustrate a remarkable evolutionary plasticity in interactions between mammalian GPCRs and C. elegans signalling machinery, spanning 800 million years of evolution. This in vivo system, which imparts novel avoidance behaviour on C. elegans, thus provides a simple means of studying and screening interaction of GPCRs with extracellular agonists, antagonists and intracellular binding partners