Wind tunnel and analytical investigation of over-the-wing propulsion/air frame interferences for a short-haul aircraft at Mach numbers from 0.6 to 0.78

Results of analytical calculations and wind tunnel tests at cruise speeds of a representative four engine short haul aircraft employing upper surface blowing (USB) with a supercritical wing are discussed. Wind tunnel tests covered a range of Mach number M from 0.6 to 0.78. Tests explored the use of three USB nozzle configurations. Results are shown for the isolated wing body and for each of the three nozzle types installed. Experimental results indicate that a low angle nacelle and streamline contoured nacelle yielded the same interference drag at the design Mach number. A high angle powered lift nacelle had higher interference drag primarily because of nacelle boattail low pressures and flow separation. Results of varying the spacing between the nacelles and the use of trailing edge flap deflections, wing upper surface contouring, and a convergent-divergent nozzle to reduce potential adverse jet effects were also discussed. Analytical comparisons with experimental data, made for selected cases, indicate favorable agreement

High-level chromate resistance in Arthrobacter sp. strain FB24 requires previously uncharacterized accessory genes

<p>Abstract</p> <p>Background</p> <p>The genome of <it>Arthrobacter </it>sp. strain FB24 contains a chromate resistance determinant (CRD), consisting of a cluster of 8 genes located on a 10.6 kb fragment of a 96 kb plasmid. The CRD includes <it>chrA</it>, which encodes a putative chromate efflux protein, and three genes with amino acid similarities to the amino and carboxy termini of ChrB, a putative regulatory protein. There are also three novel genes that have not been previously associated with chromate resistance in other bacteria; they encode an oxidoreductase (most similar to malate:quinone oxidoreductase), a functionally unknown protein with a WD40 repeat domain and a lipoprotein. To delineate the contribution of the CRD genes to the FB24 chromate [Cr(VI)] response, we evaluated the growth of mutant strains bearing regions of the CRD and transcript expression levels in response to Cr(VI) challenge.</p> <p>Results</p> <p>A chromate-sensitive mutant (strain D11) was generated by curing FB24 of its 96-kb plasmid. Elemental analysis indicated that chromate-exposed cells of strain D11 accumulated three times more chromium than strain FB24. Introduction of the CRD into strain D11 conferred chromate resistance comparable to wild-type levels, whereas deletion of specific regions of the CRD led to decreased resistance. Using real-time reverse transcriptase PCR, we show that expression of each gene within the CRD is specifically induced in response to chromate but not by lead, hydrogen peroxide or arsenate. Higher levels of <it>chrA </it>expression were achieved when the <it>chrB </it>orthologs and the WD40 repeat domain genes were present, suggesting their possible regulatory roles.</p> <p>Conclusion</p> <p>Our findings indicate that chromate resistance in <it>Arthrobacter </it>sp. strain FB24 is due to chromate efflux through the ChrA transport protein. More importantly, new genes have been identified as having significant roles in chromate resistance. Collectively, the functional predictions of these additional genes suggest the involvement of a signal transduction system in the regulation of chromate efflux and warrants further study.</p

KC-SMARTR: An R package for detection of statistically significant aberrations in multi-experiment aCGH data

Background: Most approaches used to find recurrent or differential DNA Copy Number Alterations (CNA) in array Comparative Genomic Hybridization (aCGH) data from groups of tumour samples depend on the discretization of the aCGH data to gain, loss or no-change states. This causes loss of valuable biological information in tumour samples, which are frequently heterogeneous. We have previously developed an algorithm, KC-SMART, that bases its estimate of the magnitude of the CNA at a given genomic location on kernel convolution (Klijn et al., 2008). This accounts for the intensity of the probe signal, its local genomic environment and the signal distribution across multiple samples. Results: Here we extend the approach to allow comparative analyses of two groups of samples and introduce the R implementation of these two approaches. The comparative module allows for a supervised analysis to be performed, to enable the identification of regions that are differentially aberrated between two user-defined classes. We analyzed data from a series of B- and T-cell lymphomas and were able to retrieve all positive control regions (VDJ regions) in addition to a number of new regions. A t-test employing segmented data, that we implemented, was also able to locate all the positive control regions and a number of new regions but these regions were highly fragmented. Conclusions: KC-SMARTR offers recurrent CNA and class specific CNA detection, at different genomic scales, in a single package without the need for additional segmentation. It is memory efficient and runs on a wide range of machines. Most importantly, it does not rely on data discretization and therefore maximally exploits the biological information in the aCGH data.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

Development of an invasively monitored porcine model of acetaminophen-induced acute liver failure

Background: The development of effective therapies for acute liver failure (ALF) is limited by our knowledge of the pathophysiology of this condition, and the lack of suitable large animal models of acetaminophen toxicity. Our aim was to develop a reproducible invasively-monitored porcine model of acetaminophen-induced ALF. Method: 35kg pigs were maintained under general anaesthesia and invasively monitored. Control pigs received a saline infusion, whereas ALF pigs received acetaminophen intravenously for 12 hours to maintain blood concentrations between 200-300 mg/l. Animals surviving 28 hours were euthanased. Results: Cytochrome p450 levels in phenobarbital pre-treated animals were significantly higher than non pre-treated animals (300 vs 100 pmol/mg protein). Control pigs (n=4) survived 28-hour anaesthesia without incident. Of nine pigs that received acetaminophen, four survived 20 hours and two survived 28 hours. Injured animals developed hypotension (mean arterial pressure; 40.8+/-5.9 vs 59+/-2.0 mmHg), increased cardiac output (7.26+/-1.86 vs 3.30+/-0.40 l/min) and decreased systemic vascular resistance (8.48+/-2.75 vs 16.2+/-1.76 mPa/s/m3). Dyspnoea developed as liver injury progressed and the increased pulmonary vascular resistance (636+/-95 vs 301+/-26.9 mPa/s/m3) observed may reflect the development of respiratory distress syndrome. Liver damage was confirmed by deterioration in pH (7.23+/-0.05 vs 7.45+/-0.02) and prothrombin time (36+/-2 vs 8.9+/-0.3 seconds) compared with controls. Factor V and VII levels were reduced to 9.3 and 15.5% of starting values in injured animals. A marked increase in serum AST (471.5+/-210 vs 42+/-8.14) coincided with a marked reduction in serum albumin (11.5+/-1.71 vs 25+/-1 g/dL) in injured animals. Animals displayed evidence of renal impairment; mean creatinine levels 280.2+/-36.5 vs 131.6+/-9.33 mumol/l. Liver histology revealed evidence of severe centrilobular necrosis with coagulative necrosis. Marked renal tubular necrosis was also seen. Methaemoglobin levels did not rise >5%. Intracranial hypertension was not seen (ICP monitoring), but there was biochemical evidence of encephalopathy by the reduction of Fischer's ratio from 5.6 +/- 1.1 to 0.45 +/- 0.06. Conclusion: We have developed a reproducible large animal model of acetaminophen-induced liver failure, which allows in-depth investigation of the pathophysiological basis of this condition. Furthermore, this represents an important large animal model for testing artificial liver support systems

Sources and nature of ice-nucleating particles in the free troposphere at Jungfraujoch in winter 2017

Primary ice formation in mixed-phase clouds is initiated by a minute subset of the ambient aerosol population, called ice-nucleating particles (INPs). The knowledge about their atmospheric concentration, composition, and source in cloud-relevant environments is still limited. During the 2017 joint INUIT/CLACE (Ice Nuclei research UnIT/CLoud–Aerosol Characterization Experiment) field campaign, observations of INPs as well as of aerosol physical and chemical properties were performed, complemented by source region modeling. This aimed at investigating the nature and sources of INPs. The campaign took place at the High-Altitude Research Station Jungfraujoch (JFJ), a location where mixed-phase clouds frequently occur. Due to its altitude of 3580 m a.s.l., the station is usually located in the lower free troposphere, but it can also receive air masses from terrestrial and marine sources via long-range transport. INP concentrations were quasi-continuously detected with the Horizontal Ice Nucleation Chamber (HINC) under conditions representing the formation of mixed-phase clouds at −31 ∘C. The INP measurements were performed in parallel to aerosol measurements from two single-particle mass spectrometers, the Aircraft-based Laser ABlation Aerosol MAss Spectrometer (ALABAMA) and the laser ablation aerosol particle time-of-flight mass spectrometer (LAAPTOF). The chemical identity of INPs is inferred by correlating the time series of ion signals measured by the mass spectrometers with the time series of INP measurements. Moreover, our results are complemented by the direct analysis of ice particle residuals (IPRs) by using an ice-selective inlet (Ice-CVI) coupled with the ALABAMA. Mineral dust particles and aged sea spray particles showed the highest correlations with the INP time series. Their role as INPs is further supported by source emission sensitivity analysis using atmospheric transport modeling, which confirmed that air masses were advected from the Sahara and marine environments during times of elevated INP concentrations and ice-active surface site densities. Indeed, the IPR analysis showed that, by number, mineral dust particles dominated the IPR composition (∼58 %), and biological and metallic particles are also found to a smaller extent (∼10 % each). Sea spray particles are also found as IPRs (17 %), and their fraction in the IPRs strongly varied according to the increased presence of small IPRs, which is likely due to an impact from secondary ice crystal formation. This study shows the capability of combining INP concentration measurements with chemical characterization of aerosol particles using single-particle mass spectrometry, source region modeling, and analysis of ice residuals in an environment directly relevant for mixed-phase cloud formation.</p

Quantification of topographic venting of boundary layer air to the free troposphere

International audienceNet vertical air mass export by thermally driven flows from the atmospheric boundary layer (ABL) to the free troposphere (FT) above deep Alpine valleys was investigated. The vertical export of pollutants above mountainous terrain is presently poorly represented in global chemistry transport models (GCTMs) and needs to be quantified. Air mass budgets were calculated using aircraft observations obtained in deep Alpine valleys. The results show that on average 3 times the valley air mass is exported vertically per day under fair weather conditions. During daytime the type of valleys investigated in this study can act as an efficient "air pump" that transports pollutants upward. The slope wind system within the valley plays an important role in redistributing pollutants. Nitrogen oxide emissions in mountainous regions are efficiently injected into the FT. This could enhance their ozone (O3) production efficiency and thus influences tropospheric pollution budgets. Once lifted to the FT above the Alps pollutants are transported horizontally by the synoptic flow and are subject to European pollution export. Forward trajectory studies show that under fair weather conditions two major pathways for air masses above the Alps dominate. Air masses moving north are mixed throughout the whole tropospheric column and further transported eastward towards Asia. Air masses moving south descend within the subtropical high pressure system above the Mediterranean

Activation of Central Melanocortin Pathways by Fenfluramlne

D-fenfluramine (d-FEN) was once widely prescribed and was among the most effective weight loss drugs, but was withdrawn from clinical use because of reports of cardiac complications in a subset of patients. Discerning the neurobiology underlying the anorexic action of d-FEN may facilitate the development of new drugs to prevent and treat obesity. Through a combination of functional neuroanatomy, feeding, and electrophysiology studies in rodents, we show that d-FEN-induced anorexia requires activation of central nervous system melanocortin pathways. These results provide a mechanistic explanation of d-FEN\u27s anorexic actions and indicate that drugs targeting these downstream melanocortin pathways may prove to be effective and more selective antiobesity treatments

Update on a pilot study: Flumeltbi peripheral blood HLAhaploidentical stem cell transplantation with post-transplant cyclophosphamide and bortezomib (Cy2Bor3)

Background: Bortezomib (Bor) can inhibit the proliferation of dendritic cells (DCs) and block the expression of co-receptors CD80, CD86 and secretion of cytokines IL-12 and TNF-α and hence the ability of DCs to activate T cells. We started a pilot study incorporating the addition of bortezomib to post-transplant cyclophosphamide (PTCY) in the setting of peripheral blood (PB) HLA-haploidentical stem cell transplantation (Haplo-SCT). Methods: This is a single center open label pilot study. Eligible patients received Fludarabine Melphalan TBI 200 cGy as conditioning followed by haplo-SCT and PTCY. Bor was administered at 1.3mg/m2 on day+1, 4 and 7. Tacrolimus and MMF were started at day+5. Results: Seven patients were enrolled so far, five males and 2 females. Median age was 58 years (26-60). Donors were 3 brothers, 3 sons and 1 mother. Disease risk index was high in 3, intermediate in 3 and low in 1. Three patients had AML, two had ALL and MM, one had ALL and one had CML. CMV recipient status was negative in one and positive in 6. Median HCT-CI was 3(1-4). Median CD34 and CD3 infused were 4.13 x10-6 and 1.7x10-8/ kg recipient respectively, all were cryopreserved except 2. Four patients had CRS before Cy infusion with ASTCT grade of 1. Six patients had grade 3 hypokalemia around day+ 4-5. Five patients had grade 3 mucositis and 2 had grade 1. Four patients had neutropenic fever and one patient had engraftment fever. Median neutrophils and platelets engraftment were 16 and 26 days respectively. Chimerism post SCT was \u3e =99% donor at day 30 for all patients. Six patients are off tacrolimus with median time to be off it was 187.5 days. Five pts had aGVHD with maximum grade of I in 3 patients, II in one patient and III in one patient at a median 50days post SCT. None developed early hematuria, four had late hematuria with highest grade of 4. Two patients were positive for BK virus. One patient had reactivation of CMV, 2 had EBV and one had adenovirus, all resolved. Three pts had HHV6 that resolved. Of the 5 patients who were evaluable, one developed moderate chronic GVHD. So far the median time to follow up is 455 days (70-1239) with relapse and subsequently death in one patient who had high risk AML with 3 different inductions prior to SCT. . At 1 year for 4 evaluable patients IgG were \u3e400 mg/dl and CD4 \u3e 350 cells/ul. Conclusions: Cy2Bor3 post PB Haplo-SCT was well tolerated. Although small number of patients and limited but encouraging results so far. The trial is ongoing