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Sex determination, the developmental process by which sexually dimorphic phenotypes are established, evolves fast. Evolutionary turnover in a sex determination pathway may occur via selection on alleles that are genetically linked to a new master sex determining locus on a newly formed proto-sex chromosome. Species with polygenic sex determination, in which master regulatory genes are found on multiple different proto-sex chromosomes, are informative models to study the evolution of sex determination and sex chromosomes. House flies are such a model system, with male determining loci possible on all six chromosomes and a female-determiner on one of the chromosomes as well. The two most common male-determining proto-Y chromosomes form latitudinal clines on multiple continents, suggesting that temperature variation is an important selection pressure responsible for maintaining polygenic sex determination in this species. Temperature-dependent fitness effects could be manifested through temperature-dependent gene expression differences across proto-Y chromosome genotypes. These gene expression differences may be the result of cis regulatory variants that affect the expression of genes on the proto-sex chromosomes, or trans effects of the proto-Y chromosomes on genes elswhere in the genome. We used RNA-seq to identify genes whose expression depends on proto-Y chromosome genotype and temperature in adult male house flies. We found no evidence for ecologically meaningful temperature-dependent expression differences of sex determining genes between male genotypes, but we were probably not sampling an appropriate developmental time-point to identify such effects. In contrast, we identified many other genes whose expression depends on the interaction between proto-Y chromosome genotype and temperature, including genes that encode proteins involved in reproduction, metabolism, lifespan, stress response, and immunity. Notably, genes with genotype-by-temperature interactions on expression were not enriched on the proto-sex chromosomes. Moreover, there was no evidence that temperature-dependent expression is driven by chromosome-wide cis-regulatory divergence between the proto-Y and proto-X alleles. Therefore, if temperature-dependent gene expression is responsible for differences in phenotypes and fitness of proto-Y genotypes across house fly populations, these effects are driven by a small number of temperature-dependent alleles on the proto-Y chromosomes that may have trans effects on the expression of genes on other chromosomes.

This essay discusses several key issues concerning the study of attention and its relation to visual perception, with an emphasis on behavioral and experiential aspects. It begins with an overview of several classical works carried out in the latter half of the twentieth century, such as the development of early filter and spotlight models of attention. This is followed by a survey of subsequent research that extended or modified these results in significant ways. It includes work on various forms of induced blindness and on the capabilities of nonattentional processes. It also covers proposals about how a “just-in-time” allocation of attention can create the impression that we see our surroundings in coherent detail everywhere, as well as how the failure of such allocation can result in various perceptual deficits. The final section examines issues that have not received much consideration to date, but that may be important for new lines of research in the near future. These include the prospects for a better characterization of attention, the possibility of more systematic computational explanations, factors that may significantly modulate attentional operation, and the possibility of several kinds of visual attention and visual experience. Keywords: attention; vision; perception; consciousness; visual memory; inattentional blindness; change blindness; scene perception

We present a rigorous way to evaluate the visual perception of correlation in scatterplots, based on classical psychophysical methods originally developed for simple properties such as brightness. Although scatterplots are graphically complex, the quantity they convey is relatively simple. As such, it may be possible to assess the perception of correlation in a similar way. Scatterplots were each of 5.0° extent, containing 100 points with a bivariate normal distribution. Means were 0.5 of the range of the points, and standard deviations 0.2 of this range. Precision was determined via an adaptive algorithm to find the just noticeable differences (jnds) in correlation, i.e., the difference between two side-by-side scatterplots that could be discriminated 75% of the time. Accuracy was measured by direct estimation, using reference scatterplots with fixed upper and lower values, with a test scatterplot adjusted so that its correlation appeared to be halfway between these. This process was recursively applied to yield several further estimates. Results of the discrimination tests show jnd(r) = k (1/b - r), where r is the Pearson correlation, and parameters 0 < k, b < 1. Integration yields a subjective estimate of correlation g(r) = ln(1 - br) / ln(1 - b). The values of b found via discrimination closely match those found via direct estimation. As such, it appears that the perception of correlation in a scatterplot is completely described by two related performance curves, specified by two easily-measured parameters.

The low-recycling regimes of divertor operation in a single-null NSTX magnetic configuration are studied using computer simulations with the edge plasma transport code UEDGE. The edge plasma transport properties pertinent to the low-recycling regimes are demonstrated. These include the flux-limited character of the parallel heat transport and the high plasma temperatures with the flattened profiles in the scrape-off-layer. It is shown that to maintain the balance of particle fluxes at the core interface the deuterium gas puffing rate should increase as the divertor recycling coefficient decreases. The radial profiles of the heat load to the outer divertor plate, the upstream radial plasma profiles, and the effects of the cross-field plasma transport in the low-recycling regimes are discussed. It is also shown that recycling of lithium impurities evaporating from the divertor plate at high surface temperatures can reverse the low-recycling divertor operational regime to the high-recycling one and may cause thermal instability of the divertor plate. (C) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Title. Task-oriented training in rehabilitation after stroke: systematic review. Aim. This paper is a report of a review conducted to provide an overview of the evidence in the literature on task-oriented training of stroke survivors and its relevance in daily nursing practice. Background. Stroke is the second leading cause of death and one of the leading causes of adult disability in the Western world. The use of neurodevelopmental treatment in the daily nursing care of stroke survivors does not improve clinical outcomes. Nurses are therefore exploring other forms of rehabilitation intervention, including task-oriented rehabilitation. Despite the growing number of studies showing evidence on task-oriented interventions, recommendations for daily nursing practice are lacking. Data Sources. A range of databases was searched to identify papers addressing taskoriented training in stroke rehabilitation, including Medline, CINAHL, Embase and the Cochrane Library of systematic reviews. Papers published in English between January 1996 and September 2007 were included. There were 42 papers in the final dataset, including nine systematic reviews. Review methods. The selected randomized controlled trials and systematic reviews were assessed for quality. Important characteristics and outcomes were extracted and summarized. Results. Studies of task-related training showed benefits for functional outcome compared with traditional therapies. Active use of task-oriented training with stroke survivors will lead to improvements in functional outcomes and overall healthrelated quality of life. Conclusion. Generally, task-oriented rehabilitation proved to be more effective. Many interventions are feasible for nurses and can be performed in a ward or at home. Nurses can and should play an important role in creating opportunities to practise meaningful functional tasks outside of regular therapy sessions.

Plasma proteins such as early complement components and IgM are involved in the removal of late apoptotic or secondary necrotic (sn) cells. We have recently described how a plasma protease that could be inhibited by the protease inhibitor aprotinin was essential to remove nucleosomes from sn cells. An obvious candidate, plasmin, did indeed have nucleosome-releasing factor (NRF) activity. However, recalcified plasma (r-plasma) retained its NRF activity after plasminogen depletion, which suggests the existence of another protease responsible for NRF activity in plasma. In this study we have used size-exclusion and anion-exchange chromatography to purify the protease responsible for NRF activity in plasma. SDS-PAGE analysis of chromatography fractions containing NRF activity revealed a protein band corresponding with NRF activity. Sequence analysis showed this band to be factor VII-activating protease (FSAP). We developed monoclonal antibodies to FSAP and were able to completely inhibit NRF activity in plasma with monoclonal antibodies to FSAP. Using affinity chromatography we were able to purify single-chain (sc) FSAP from r-plasma. Purified scFSAP efficiently removes nucleosomes from sn cells. We report that factor VII-activating protease may function in cellular homeostasis by catalyzing the release of nucleosomes from secondary necrotic cells.

Cultivated and wild potatoes contain a major disease-resistance cluster on the short arm of chromosome V, including the R1 resistance (R) gene against potato late blight. To explore the functional and evolutionary significance of clustering in the generation of novel disease-resistance genes, we constructed three approximately 1 Mb physical maps in the R1 gene region, one for each of the three genomes (haplotypes) of allohexaploid Solanum demissum, the wild potato progenitor of the R1 locus. Totals of 691, 919 and 559 kb were sequenced for each haplotype, and three distinct resistance-gene families were identified, one homologous to the potato R1 gene and two others homologous to either the Prf or the Bs4 R-gene of tomato. The regions with R1 homologues are highly divergent among the three haplotypes, in contrast to the conserved flanking non-resistance gene regions. The R1 locus shows dramatic variation in overall length and R1 homologue number among the three haplotypes. Sequence comparisons of the R1 homologues show that they form three distinct clades in a distance tree. Frequent sequence exchanges were detected among R1 homologues within each clade, but not among those in different clades. These frequent sequence exchanges homogenized the intron sequences of homologues within each clade, but did not homogenize the coding sequences. Our results suggest that the R1 homologues represent three independent groups of fast-evolving type I resistance genes, characterized by chimeric structures resulting from frequent sequence exchanges among group members. Such genes were first identified among clustered RGC2 genes in lettuce, where they were distinguished from slow-evolving type II R-genes. Our findings at the R1 locus in S. demissum may indicate that a common or similar mechanism underlies the previously reported differentiation of type I and type II R-genes and the differentiation of type I R-genes into distinct groups, identified here.

Cerebral amyloid angiopathy is one of the characteristics of Alzheimer's disease (AD) and this accumulation of fibrillar amyloid-beta (Alphabeta) in the vascular wall is accompanied by marked vascular damage. In vitro, Abeta1-40 carrying the 'Dutch' mutation (DAbeta1-40) induces degeneration of cultured human brain pericytes (HBP). To identify possible intracellular mediators of Abeta-induced cell death, a comparative cDNA expression array was performed to detect differential gene expression of Abeta-treated vs. untreated HBP. Messenger RNA expression of cyclin D1, integrin beta4, defender against cell death-1, neuroleukin, thymosin beta10, and integrin alpha5 were increased in DAbeta1-40-treated HBP, whereas insulin-like growth factor binding protein-2 mRNA expression was decreased. Corresponding protein expression was investigated in AD and control brains to explore a potential role for these proteins in pathological lesions of the AD brain. Cyclin D1 expression was increased in cerebral amyloid angiopathy and cells in a perivascular position, suggesting that the cell cycle may be disturbed during Abeta-mediated degeneration of cerebrovascular cells. Moreover, cyclin D1 expression, but also that of integrin beta4, defender against cell death-1, neuroleukin and thymosin beta10 was found in a subset of senile plaques, suggesting a role for these proteins in the pathogenesis of senile plaques.

In various chemical processes thorough homogeneous mixing is of great importance. Due to their small characteristic dimensions, micromixers have a great potential to achieve fast and uniform mixing. However, in the field of powder synthesis from precipitation processes the use of standard micromixers is severely limited because of rapid clogging of the microchannels. As an alternative, mixing nozzles which are less susceptible to fouling can provide a sufficient mixing quality. The flow field and fluid distribution inside multi-fluid droplets during droplet formation is simulated. Depending on the geometry and flow rates, complex velocity fields and flow distributions are found and the impact on the mixing efficiency is qualitatively deduced. Furthermore, we point out how the tendency of fouling can be further reduced with the help of improved nozzle geometries.

Flowing liquid walls have been proposed as the first wall and/or divertor plates for magnetic fusion energy devices because they may solve a number of technological problems for fusion power plants. A key question for their successful use is the edge-plasma shielding of wall-vapor impurities from the core plasma. A self-consistent analysis of the combined hydrogen/impurity edge plasmas for distributed wall impurity sources is performed using the two-dimension fluid transport code UEDGE for tokamak parameters. Three regimes of edge-plasma response are identified. Comparisons are made between previous results for lithium (from Li or SnLi walls) and fluorine (from the molten salt Flibe walls), and new results for Sn (from Sn walls). Owing to its lower vapor pressure, Sn is found to have the lowest impact on the edge and core plasma. For the Sn wall, the effects of toroidal versus slab geometries are studied, as well as the influence of spatial variations in evaporation fluxes.

This article develops a nondimensional equation of the concentration field inside the droplet, which involves a characteristic nondimensional parameter. The equation describes the diffusional mass transport inside the droplet during the drying process and accounts for the mass transfer across the droplet surface. The parameter is formed from the Sherwood number of mass transfer into the gaseous ambient medium, the vapour concentration in the ambient medium, the density of the liquid and the gas, and the binary diffusion coefficients of the diffusing component in the liquid and in the gas. An experimental verification confirms the role of the parameter and the correctness of the threshold value for the substances investigated.

An acoustic tube levitator was developed and used for investigating the drying behavior of single droplets (d D,0 ≃1.0 mm) containing water and a certain fraction of inert, solid material such as glass beads with a mean diameter of d s =30 μm. A glass tube surrounds the transducer and reflector of the acoustic tube levitator, hence increases the radial stability of the droplet and shields it against disturbances from outside. A CCD camera and a back-light illumination are used to observe the evolution of the droplet diameter and the vertical position of the droplet. Ambient temperature, initial volume and initial solid mass fraction of the droplet were systematically varied. From the measured droplet diameter and the position of the mean density, the moisture content and the mean porosity of the drying droplet/grain can be determined as a function of time.

We describe recent modifications to the UEDGE code for simulation of full double-null magnetic configurations. We present simulation results for magnetically balanced double nulls, with and without asymmetries due to divertor recycling and cross-field drifts. Up/down electron temperature asymmetries due to recycling are weak for attached plasmas. Cross-field drifts due to radial electric fields produce strong ion particle fluxes through the private flux regions that drive up/down plasma asymmetries. Electrical currents through grounded divertor plates are sensitive to both recycling-driven and drift-driven asymmetries.

Benchmarks of DEGAS 2 against EIRENE yield agreement to within 5% and comparable single processor run times. DEGAS 2 demonstrates a nearly linear increase in processing speed with the number of parallel processors. That speed is put to practical use here in the first runs of UEDGE coupled to DEGAS 2. The results of the coupled codes match those of coupled UEDGE and EIRENE. Additional algorithmic improvements such as use of the correlated sampling technique promise to make runs of the coupled UEDGE - DEGAS 2 codes practical for everyday use.

Interleukin 6 plays a key role in the pathogenesis of multiple myeloma (MM). Therefore we conducted a phase I dose-escalating study with chimaeric monoclonal anti-IL6 antibodies (cMab) in MM patients resistant to second-line chemotherapy. The cMab (CLB IL6/8; Kd 6.25 x 10(-12)M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28, repectively, with a daily dose of 5 mg in patients 1-3, 10 mg in patients 4-6, 20 mg in patients 7-9 and 40mg in patients 10-12 (total dose 140 mg, 280mg, 560 mg and 1120 mg of anti-IL6, respectively). 11/12 patients had elevated pretreatment IL6 levels. Except for transient thrombocytopenia in two patients there was no toxicity. There were no changes in haemoglobin levels, granulocyte count, liver enzymes or renal function. No human anti-chimaeric antibodies were induced. This was also reflected in a long half-life time of the cMab (median 17.8 d), resulting in accumulation of the anti-IL6 cMab and high levels of circulating IL6. However, this was in the form of biologically inactive IL6/cMab complexes and did not result in acceleration of the disease. Although C-reactive protein (CRP) levels were decreased to below detection level in 11/12 patients, indicating effective IL6 blocking, none of the patients achieved a response according to the standard criteria. We conclude that this chimaeric anti-IL6 Mab has a low toxicity, low immunogenicity and a long T1/2. A dose of 40 mg/d for 14 d can safely be used in future phase II studies.

The features of the fully implicit 2-D fluid code UEDGE are described. The utility of the code is demonstrated by showing bifurcations or multiple solutions of the tokamak edge plasma for both deuterium and impurity injection in the divertor.

Comparisons between a 2-D fluid simulation of the scrape-off-layer (SOL) plasma of a diverted tokamak and experimental data from the DIII-D are shown. It is concluded that a simple diffusive model for perpendicular transport is consistent with the data. Discrepancies in the simulation suggest that impurity radiation may be playing a significant role in the experiment, and that further work is required to understand hydrogen recycling at the divertor.

We have examined the regulation of interleukin (IL)-4 production by human peripheral blood T cells. Production of IL-4 was shown to be regulated differently from IL-2 and interferon(IFN)-gamma production. Stimulation of peripheral blood lymphocytes with anti-CD3, anti-CD2, anti-CD28, Phorbol 12-myristate 13-acetate (PMA) or IL-2 as a single stimulant did not induce IL-4 production. However, combinations of anti-CD2 with either anti-CD28 or IL-2 resulted in IL-4 production, peaking at days 3-4. Stimulation with anti-CD3 instead of anti-CD2 gave similar results, but was less potent. After days 3-4, IL-4 levels decreased, most likely due to consumption of IL-4. PMA profoundly affected cytokine production, it enhanced IL-2 production by at least tenfold, whereas, in the same cell population, IL-4 production was almost completely inhibited. This was observed at the protein as well as at the mRNA level. In contrast, agents that increase intracellular cAMP levels inhibited IL-2 production but left IL-4 production unaffected. IFN-gamma production behaved similar to IL-2 production but the effects were less outspoken.

The effects of plasma currents and cross-field drifts on single null tokamak divertor operation are simulated using a fully implicit 2-D fluid code. Equations solved are those for particle continuity, parallel momentum, electron energy, ion energy, electrostatic potential, and neutral gas diffusion. The core and scrape-off layer regions are separated by a magnetic separatrix, both of which are included in the simulation. The core plasma is poloidally periodic, and the inner and outer private flux regions are properly connected. The code utilizes a fully implicit method-of-lines scheme to advance the variables in time with a Krylov technique or a direct Newton iteration with a numerical Jacobian. Results are presented on the effects of currents and cross-field drifts for DIII-D single-null parameters.