The Effect of wake Turbulence Intensity on Transition in a Compressor Cascade

Direct numerical simulations of separating flow along a section at midspan of a low-pressure V103 compressor cascade with periodically incoming wakes were performed. By varying the strength of the wake, its influence on both boundary layer separation and bypass transition were examined. Due to the presence of small-scale three-dimensional fluctuations in the wakes, the flow along the pressure surface undergoes bypass transition. Only in the weak-wake case, the boundary layer reaches a nearly-separated state between impinging wakes. In all simulations, the flow along the suction surface was found to separate. In the simulation with the strong wakes, separation is intermittently suppressed as the periodically passing wakes managed to trigger turbulent spots upstream of the location of separation. As these turbulent spots convect downstream, they locally suppress separation. © 2014 Springer Science+Business Media Dordrecht

Determining solar effects in Neptune’s atmosphere

Long-duration observations of Neptune’s brightness in two visible wavelengths provide a disk-averaged estimate of its atmospheric aerosol. Brightness variations were previously associated with the 11-year solar cycle, through solar-modulated mechanisms linked with either ultra-violet (UV) or galactic cosmic ray (GCR) effects on atmospheric particles. Here we use a recently extended brightness dataset (1972-2014), with physically realistic modelling to show that rather than alternatives, UV and GCR are likely to be modulating Neptune’s atmosphere in combination. The importance of GCR is further supported by the response of Neptune's atmosphere to an intermittent 1.5 to 1.9 year periodicity, which occurred preferentially in GCR (not UV) during the mid-1980s. This periodicity was detected both at Earth, and in GCR measured by Voyager 2, then near Neptune. A similar coincident variability in Neptune’s brightness suggests nucleation onto GCR ions. Both GCR and UV mechanisms may occur more rapidly than the subsequent atmospheric particle transport

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

Coastal clustering of HEV; Cornwall, UK.

PublishedBACKGROUND AND AIMS: Autochthonous hepatitis E virus (HEV) infection is a porcine zoonosis and increasingly recognized in developed countries. In most cases the route of infection is uncertain. A previous study showed that HEV was associated geographically with pig farms and coastal areas. AIM: The aim of the present research was to study the geographical, environmental and social factors in autochthonous HEV infection. METHODS: Cases of HEV genotype 3 infection and controls were identified from 2047 consecutive patients attending a rapid-access hepatology clinic. For each case/control the following were recorded: distance from home to nearest pig farm, distance from home to coast, rainfall levels during the 8 weeks before presentation, and socioeconomic status. RESULTS: A total of 36 acute hepatitis E cases, 170 age/sex-matched controls and 53 hepatitis controls were identified. The geographical spread of hepatitis E cases was not even when compared with both control groups. Cases were more likely to live within 2000 m of the coast (odds ratio=2.32, 95% confidence interval=1.08-5.19, P=0.03). There was no regional difference in the incidence of cases and controls between west and central Cornwall. There was no difference between cases and controls in terms of distance from the nearest pig farm, socioeconomic status or rainfall during the 8 weeks before disease presentation. CONCLUSION: Cases of HEV infection in Cornwall are associated with coastal residence. The reason for this observation is uncertain, but might be related to recreational exposure to beach areas exposed to HEV-contaminated 'run-off' from pig farms. This hypothesis merits further study.The European Centre for the Environment and Human Health (part of the Peninsula College of Medicine and Dentistry which is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West) is supported by investment from the European Regional Development Fund and the European Social Fund Convergence Programme for Cornwall and the Isles of Scilly

ICTV Virus Taxonomy Profile: Rhabdoviridae.

This is the final version of the article. Available from the publisher via the DOI in this record.The family Rhabdoviridae comprises viruses with negative-sense (-) single-stranded RNA genomes of 10.8-16.1 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants and animals including mammals, birds, reptiles and fish, as well as arthropods which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish and agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of Rhabdoviridae, which is available at www.ictv.global/report/rhabdoviridae.Production of this summary, the online chapter, and associated resources was funded by a grant from the Wellcome Trust (WT108418AIA)

Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the antibody repertoire. Here we review the evidence for antibodies (to self-antigens as well as infectious organism and dietary antigens) as biomarkers of diagnosis, prognosis, and treatment response in psychotic disorders. Neuronal autoantibodies have current, and increasing, clinical utility in the diagnosis of organic or atypical psychosis syndromes. Antibodies to selected infectious agents show some promise in predicting cognitive impairment and possibly other symptom domains (eg, suicidality) within psychotic disorders. Finally, infectious antibodies and neuronal and other autoantibodies have recently emerged as potential biomarkers of response to anti-infective therapies, immunotherapies, or other novel therapeutic strategies in psychotic disorders, and have a clear role in stratifying patients for future clinical trials. As in nonpsychiatric disorders, combining biomarkers and large-scale use of "bottom-up" approaches to biomarker identification are likely to maximize the eventual clinical utility of antibody biomarkers in psychotic disorders

Microfluidic systems for the analysis of the viscoelastic fluid flow phenomena in porous media

In this study, two microfluidic devices are proposed as simplified 1-D microfluidic analogues of a porous medium. The objectives are twofold: firstly to assess the usefulness of the microchannels to mimic the porous medium in a controlled and simplified manner, and secondly to obtain a better insight about the flow characteristics of viscoelastic fluids flowing through a packed bed. For these purposes, flow visualizations and pressure drop measurements are conducted with Newtonian and viscoelastic fluids. The 1-D microfluidic analogues of porous medium consisted of microchannels with a sequence of contractions/ expansions disposed in symmetric and asymmetric arrangements. The real porous medium is in reality, a complex combination of the two arrangements of particles simulated with the microchannels, which can be considered as limiting ideal configurations. The results show that both configurations are able to mimic well the pressure drop variation with flow rate for Newtonian fluids. However, due to the intrinsic differences in the deformation rate profiles associated with each microgeometry, the symmetric configuration is more suitable for studying the flow of viscoelastic fluids at low De values, while the asymmetric configuration provides better results at high De values. In this way, both microgeometries seem to be complementary and could be interesting tools to obtain a better insight about the flow of viscoelastic fluids through a porous medium. Such model systems could be very interesting to use in polymer-flood processes for enhanced oil recovery, for instance, as a tool for selecting the most suitable viscoelastic fluid to be used in a specific formation. The selection of the fluid properties of a detergent for cleaning oil contaminated soil, sand, and in general, any porous material, is another possible application

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.</p> <p>Methods/Design</p> <p>This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 (¹²⁵I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with ¹²⁵I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during ¹²⁵I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.</p> <p>The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.</p> <p>Discussion</p> <p>To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.</p> <p>Trial registration</p> <p>UMIN000003992</p