The role of Stewartson and Ekman layers in turbulent rotating Rayleigh-B\'enard convection

When the classical Rayleigh-B\'enard (RB) system is rotated about its vertical axis roughly three regimes can be identified. In regime I (weak rotation) the large scale circulation (LSC) is the dominant feature of the flow. In regime II (moderate rotation) the LSC is replaced by vertically aligned vortices. Regime III (strong rotation) is characterized by suppression of the vertical velocity fluctuations. Using results from experiments and direct numerical simulations of RB convection for a cell with a diameter-to-height aspect ratio equal to one at $Ra \sim 10^8-10^9$ ($Pr=4-6$) and $0 \lesssim 1/Ro \lesssim 25$ we identified the characteristics of the azimuthal temperature profiles at the sidewall in the different regimes. In regime I the azimuthal wall temperature profile shows a cosine shape and a vertical temperature gradient due to plumes that travel with the LSC close to the sidewall. In regime II and III this cosine profile disappears, but the vertical wall temperature gradient is still observed. It turns out that the vertical wall temperature gradient in regimes II and III has a different origin than that observed in regime I. It is caused by boundary layer dynamics characteristic for rotating flows, which drives a secondary flow that transports hot fluid up the sidewall in the lower part of the container and cold fluid downwards along the sidewall in the top part.Comment: 21 pages, 12 figure

Integraal veiligheidsbeleid en planverplichting:Versteviging gemeentelijke regierol?

De wetgever wil de ‘regierol’ van de gemeente ten aanzien van het lokaal veiligheidsbeleid verstevigen. Daartoe is een wetsvoorstel aanhangig waarin de gemeenteraad wordt opgedragen om eens in de vier jaar een integraal veiligheidsplan vast te stellen. In dit artikel wordt de nut en noodzaak van deze planverplichting bestudeerd. Leidt dit wetsvoorstel tot een verandering van de gemeentelijke praktijk? En wat draagt een plan bij aan de uitoefening van de regierol van het gemeentebestuur? Deze vragen worden beantwoord aan de hand van een empirisch onderzoek naar de aanwezigheid, inhoud en functie van gemeentelijke veiligheidsplannen. Geconcludeerd wordt dat veel gemeenten al over een veiligheidsplan beschikken, maar dat de kwaliteit te wensen overlaat. Uit een casestudy blijkt dat veiligheidsproblemen in de praktijk worden opgelost zonder dat er een veiligheidsplan aan te pas komt

Imidazole-imidazole hydrogen bonding in the pH-sensing histidine side chains of influenza A M2.

The arrangement of histidine side chains in influenza A M2 tetramer determines their pKa values, which define pH-controlled proton conduction critical to the virus lifecycle. Both water-associated and hydrogen-bonded imidazole-imidazolium histidine quaternary structures have been proposed, based on crystal structures and NMR chemical shifts, respectively. Here we show, using the conduction domain construct of M2 in lipid bilayers, that the imidazole rings are hydrogen bonded even at a pH of 7.8 in the neutral charge state. An intermolecular 8.9 ± 0.3 Hz 2hJNN hydrogen bond is observed between H37 Nε and Nδ recorded in a fully protonated sample with 100 kHz magic-angle spinning. This interaction could not be detected in the drug-bound sample

Targeted therapy of the XIAP/proteasome pathway overcomes TRAIL-resistance in carcinoma by switching apoptosis signaling to a Bax/Bak-independent 'type I' mode

TRAIL is a promising anticancer agent, capable of inducing apoptosis in a wide range of treatment-resistant tumor cells. In 'type II' cells, the death signal triggered by TRAIL requires amplification via the mitochondrial apoptosis pathway. Consequently, deregulation of the intrinsic apoptosis-signaling pathway, for example, by loss of Bax and Bak, confers TRAIL-resistance and limits its application. Here, we show that despite resistance of Bax/Bak double-deficient cells, TRAIL-treatment resulted in caspase-8 activation and complete processing of the caspase-3 proenzymes. However, active caspase-3 was degraded by the proteasome and not detectable unless the XIAP/proteasome pathway was inhibited. Direct or indirect inhibition of XIAP by RNAi, Mithramycin A or by the SMAC mimetic LBW-242 as well as inhibition of the proteasome by Bortezomib overcomes TRAIL-resistance of Bax/Bak double-deficient tumor cells. Moreover, activation and stabilization of caspase-3 becomes independent of mitochondrial death signaling, demonstrating that inhibition of the XIAP/proteasome pathway overcomes resistance by converting 'type II' to 'type I' cells. Our results further demonstrate that the E3 ubiquitin ligase XIAP is a gatekeeper critical for the 'type II' phenotype. Pharmacological manipulation of XIAP therefore is a promising strategy to sensitize cells for TRAIL and to overcome TRAIL-resistance in case of central defects in the intrinsic apoptosis-signaling pathway

Identifying inhibitory compounds in lignocellulosic biomass hydrolysates using an exometabolomics approach

BACKGROUND: Inhibitors are formed that reduce the fermentation performance of fermenting yeast during the pretreatment process of lignocellulosic biomass. An exometabolomics approach was applied to systematically identify inhibitors in lignocellulosic biomass hydrolysates. RESULTS: We studied the composition and fermentability of 24 different biomass hydrolysates. To create diversity, the 24 hydrolysates were prepared from six different biomass types, namely sugar cane bagasse, corn stover, wheat straw, barley straw, willow wood chips and oak sawdust, and with four different pretreatment methods, i.e. dilute acid, mild alkaline, alkaline/peracetic acid and concentrated acid. Their composition and that of fermentation samples generated with these hydrolysates were analyzed with two GC-MS methods. Either ethyl acetate extraction or ethyl chloroformate derivatization was used before conducting GC-MS to prevent sugars are overloaded in the chromatograms, which obscure the detection of less abundant compounds. Using multivariate PLS-2CV and nPLS-2CV data analysis models, potential inhibitors were identified through establishing relationship between fermentability and composition of the hydrolysates. These identified compounds were tested for their effects on the growth of the model yeast, Saccharomyces. cerevisiae CEN.PK 113-7D, confirming that the majority of the identified compounds were indeed inhibitors. CONCLUSION: Inhibitory compounds in lignocellulosic biomass hydrolysates were successfully identified using a non-targeted systematic approach: metabolomics. The identified inhibitors include both known ones, such as furfural, HMF and vanillin, and novel inhibitors, namely sorbic acid and phenylacetaldehyde

Communicating Processes with Data for Supervisory Coordination

We employ supervisory controllers to safely coordinate high-level discrete(-event) behavior of distributed components of complex systems. Supervisory controllers observe discrete-event system behavior, make a decision on allowed activities, and communicate the control signals to the involved parties. Models of the supervisory controllers can be automatically synthesized based on formal models of the system components and a formalization of the safe coordination (control) requirements. Based on the obtained models, code generation can be used to implement the supervisory controllers in software, on a PLC, or an embedded (micro)processor. In this article, we develop a process theory with data that supports a model-based systems engineering framework for supervisory coordination. We employ communication to distinguish between the different flows of information, i.e., observation and supervision, whereas we employ data to specify the coordination requirements more compactly, and to increase the expressivity of the framework. To illustrate the framework, we remodel an industrial case study involving coordination of maintenance procedures of a printing process of a high-tech Oce printer.Comment: In Proceedings FOCLASA 2012, arXiv:1208.432

Process evaluation of a stepped-care program to prevent depression in primary care: patients' and practice nurses' experiences

Background: Depression is common in patients with diabetes type 2 (DM2) and/or coronary heart disease (CHD), with high personal and societal burden and may even be preventable. Recently, a cluster randomized trial of stepped care to prevent depression among patients with DM2 and/or CHD and subthreshold depression in Dutch primary care (Step-Dep) versus usual care showed no effectiveness. This paper presents its process evaluation, exploring in-depth experiences from a patient and practice nurse perspective to further understand the results. Methods: A qualitative study was conducted. Using a purposive sampling strategy, data were collected through semi-structured interviews with 24 participants (15 patients and nine practice nurses). All interviews were audiotaped and transcribed verbatim. Atlas.ti 5.7.1 software was used for coding and structuring of themes. A thematic analysis of the data was performed. Results: The process evaluation showed, even through a negative trial, that Step-Dep was perceived as valuable by both patients and practice nurses; perceived effectiveness on improving depressive symptoms varied greatly, but most felt that it had been beneficial for patients' well-being. Facilitators were: increased awareness of mental health problems in chronic disease management and improved accessibility and decreased experienced stigma of receiving mental health care. The Patient Health Questionnaire 9 (PHQ-9), used to determine depression severity, functioned as a useful starting point for the conversation on mental health and patients gained more insight into their mental health by regularly filling out the PHQ-9. However, patients and practice nurses did not widely support its use for monitoring depressive symptoms or making treatment decisions. Monitoring mental health was deemed important in chronically ill patients by both patients and practice nurses and was suggested to start at the time of diagnosis of a chronic disease. Appointed barriers were that patients were primarily motivated to participate in scientific research rather than their intrinsic need to improve depressive symptoms. Additionally, various practice nurses preferred offering individually based therapy over pre-determined interventions in a protocolled sequence and somatic practice nurses expressed a lack of competence to recognise and treat mental health problems. Conclusion: This study demonstrates both the benefits and unique demands of programs such as Step-Dep. The appointed facilitators and barriers could guide the development of future studies aiming to prevent depression in similar patient groups