Vertical Structure and Turbulent Saturation Level in Fully Radiative Protoplanetary Disc Models

We investigate a massive ($\varSigma \sim 10000 g cm^{-2}$ at 1 AU) protoplanetary disc model by means of 3D radiation magnetohydrodynamics simulations. The vertical structure of the disc is determined self-consistently by a balance between turbulent heating caused by the MRI and radiative cooling. Concerning the vertical structure, two different regions can be distinguished: A gas-pressure dominated, optically thick midplane region where most of the dissipation takes place, and a magnetically dominated, optically thin corona which is dominated by strong shocks. At the location of the photosphere, the turbulence is supersonic ($M \sim 2$), which is consistent with previous results obtained from the fitting of spectra of YSOs. It is known that the turbulent saturation level in simulations of MRI-induced turbulence does depend on numerical factors such as the numerical resolution and the box size. However, by performing a suite of runs at different resolutions (using up to 64x128x512 grid cells) and with varying box sizes (with up to 16 pressure scaleheights in the vertical direction), we find that both the saturation levels and the heating rates show a clear trend to converge once a sufficient resolution in the vertical direction has been achieved.Comment: 11 pages, 10 figures, accepted for publication in MNRA

Parametric study of modern airship productivity

A method for estimating the specific productivity of both hybrid and fully buoyant airships is developed. Various methods of estimating structural weight of deltoid hybrids are discussed and a derived weight estimating relationship is presented. Specific productivity is used as a figure of merit in a parametric study of fully buoyant ellipsoidal and deltoid hybrid semi-buoyant vehicles. The sensitivity of results as a function of assumptions is also determined. No airship configurations were found to have superior specific productivity to transport airplanes

Effects of Lysophosphatidic Acid (LPA) and Antidiuretic Hormone (ADH) on Cl- Secretory Responses in Polycystic Kidney Disease (PKD)

poster abstractPolycystic kidney disease (PKD) is a genetic disease that causes the formation of fluid-filled cysts in the kidney and other organs such as the liver and pancreas. Kidney function is seemingly unaltered despite substantial cyst development over the first four to six decades of life, but then the decline in renal function is precipitous often leading to complete renal failure in 5 years. Antidiuretic hormone (ADH) causes an increase in Cl- secretion into the cyst lumen, and one of the drugs in human clinical trials for treatment of PKD is an ADH receptor antagonist. The hormone works by stimulating cAMP production, which leads to the Cl- secretion. Interestingly, we have found that cyst fluid from human patients also causes a secretory Cl- flux that can lead to the growth of the remaining intact cysts. The active component of the cyst fluid is LPA, a phospholipid that acts as an extracellular signaling molecule. This secretion is important in late stage disease when large cysts are likely to leak or burst contributing to the rapid decline in renal function. Electrophysiological techniques were implemented to compare the ion fluxes stimulated by ADH and LPA. In the mpkCCDc14 (mouse principal cells of the cortical collecting duct clone 4) cell line we found that the Cl- secretory pathways stimulated by the two factors are separate and independent. Further indication of this separation is our finding that LPA stimulation does not increase cAMP levels. Therefore we have identified an additional target for potential pharmaceutical intervention in the treatment of PKD

Inhibition of cyst growth in PCK and Wpk rat models of polycystic kidney disease with low doses of peroxisome proliferator-activated receptor γ agonists

Background and Objectives The studies were designed to test the efficacy of two peroxisome proliferator-activated receptor γ (PPARγ) agonists in two rodent models of polycystic kidney disease (PKD). Materials and Methods The PCK rat is a slowly progressing cystic model while the Wpk-/- rat is a rapidly progressing model. PCK rats were fed with a pharmacological (0.4 mg/kg body weight [BW]) and a sub-pharmacological (0.04 mg/kg BW) dose of rosiglitazone (week 4–28). Wpk-/- rats were fed with pharmacological (2.0 mg/kg BW) and sub-pharmacologic (0.2 mg/kg BW) doses of pioglitazone from day 5 to 18. At termination, kidney weights of treated versus untreated cystic animals were used to determine efficacy. The current studies were also compared with previous studies containing higher doses of PPARγ agonists. The concentrations used in the animals were calculated with reference to equivalent human doses for both drugs. Results The current studies demonstrate: 1) that low, pharmacologically relevant, doses of the PPARγ agonists effectively inhibit cyst growth; 2) there is a class action of the drugs with both commercially available PPARγ agonists, rosiglitazone, and pioglitazone, inhibiting cyst growth; 3) the drugs showed efficacy in two different preclinical cystic models. In the PCK rat, animals fed with a sub-pharmacological dose of rosiglitazone for 24 weeks had significantly lower kidney weights than untreated animals (3.68 ± 0.13 g vs. 4.17 ± 0. 11 g, respectively, P < 0.01) while treatment with a pharmacologic dose had no significant effect on kidney weight. The rapidly progressing Wpk-/- rats were fed with pharmacological and sub-pharmacologic doses of pioglitazone from day 5 to 18 and the kidneys were compared with non-treated, cystic animals. Kidney weights on the pharmacologic dose were not statistically lower than the untreated animals while rats fed a sub-pharmacologic dose showed a significant decrease compared with untreated animals (3.35 ± 0.15 g vs. 4.55 ± 0.46 g, respectively, P = 0.045). Conclusion Concentrations of PPARγ agonists below the human equivalent diabetic doses are effective in slowing cyst growth in two rodent models of PKD

Protease inhibitors prevent plasminogen-mediated, but not pemphigus vulgaris-induced, acantholysis in human epidermis

Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. It is caused by autoantibodies directed against desmosomes, which are the principal adhesion structures between epidermal keratinocytes. Binding of autoantibodies leads to the destruction of desmosomes resulting in the loss of cell-cell adhesion (acantholysis) and epidermal blisters. The plasminogen activator system has been implicated as a proteolytic effector in pemphigus. We have tested inhibitors of the plasminogen activator system with regard to their potential to prevent pemphigus-induced cutaneous pathology. In a human split skin culture system, IgG preparations of sera from pemphigus vulgaris patients caused histopathologic changes (acantholysis) similar to those observed in the original pemphigus disease. All inhibitors that were tested (active site inhibitors directed against uPA, tPA, and/or plasmin; antibodies neutralizing the enzymatic activity of uPA or tPA; substances interfering with the binding of uPA to its specific cell surface receptor uPAR) failed to prevent pemphigus vulgaris IgG-mediated acantholysis. Plasminogen-mediated acantholysis, however, was effectively antagonized by the synthetic active site serine protease inhibitor WX-UK1 or by p-aminomethylbenzoic acid. Our data argue against applying anti-plasminogen activator/anti-plasmin strategies in the management of pemphigus

A Cerberus‐Inspired Anti‐Infective Multicomponent Gatekeeper Hydrogel against Infections with the Emerging “Superbug” Yeast Candida auris

The pathogenic yeast Candida auris has received increasing attention due to its ability to cause fatal infections, its resistance toward important fungicides, and its ability to persist on surfaces including medical devices in hospitals. To brace health care systems for this considerable risk, alternative therapeutic approaches such as antifungal peptides are urgently needed. In clinical wound care, a significant focus has been directed toward novel surgical (wound) dressings as first defense lines against C. auris. Inspired by Cerberus the Greek mythological “hound of Hades” that prevents the living from entering and the dead from leaving hell, the preparation of a gatekeeper hybrid hydrogel is reported featuring lectin-mediated high-affinity immobilization of C. auris cells from a collagen gel as a model substratum in combination with a release of an antifungal peptide drug to kill the trapped cells. The vision is an efficient and safe two-layer medical composite hydrogel for the treatment of severe wound infections that typically occur in hospitals. Providing this new armament to the repertoire of possibilities for wound care in critical (intensive care) units may open new routes to shield and defend patients from infections and clinical facilities from spreading and invasion of C. auris and probably other fungal pathogens

ifo Konjunkturprognose 2005/2006: Nur zögerliche Erholung

Die Weltwirtschaft hat im laufenden Jahr merklich an Dynamik eingebüßt, nachdem sie 2004 außerordentlich stark gewachsen war. In Deutschland fehlen die binnenwirtschaftlichen Auftriebskräfte immer noch fast vollständig. Die gesamtwirtschaftliche Produktion kommt sofort aus dem Tritt, sobald vom Ausland geringere Impulse ausgehen. Für die deutsche Wirtschaft ist eine fundamentale Wachstumsschwäche zu diagnostizieren; das Produktionspotential steigt derzeit nur um 1%, das ist halb so hoch wie im restlichen Euroraum. Die Entwicklung dieses und des kommenden Jahres wird ungefähr dem Trend folgen. Das reale Bruttoinlandsprodukt dürfte im Jahresdurchschnitt 2005 um 0,8% expandieren, nach 1,6% im Jahr 2004. Im nächsten Jahr dürfte sich das Expansionstempo der gesamtwirtschaftlichen Produktion parallel zur Besserung der Weltkonjunktur wieder leicht beschleunigen; die Zuwachsrate des realen Bruttoinlandsprodukts dürfte sich dann auf 1,2% belaufen. Damit wird die gesamtwirtschaftliche Auslastung der Produktionskapazitäten wieder zunehmen. Die Inflationsrate dürfte trotz des Ölpreisschubs im Durchschnitt des Prognosezeitraums unter der 2-Prozentmarke liegen. Auf dem deutschen Arbeitsmarkt ist bisher keine Wende eingetreten. Im Mai dieses Jahres gab es 4,81 Mill. registrierte Arbeitslose; das entspricht einem Anstieg von 510 000 gegenüber dem vergleichbaren Vorjahresmonat. Der überwiegende Teil dieser Zunahme (ca. 360 000) ist auf die im Zuge der Hartz-IV-Gesetzgebung erfolgte Zusammenlegung von Arbeitslosen- und Sozialhilfe zurückzuführen. Rechnet man dagegen, dass inzwischen rund 155 000 Zusatzjobs die Statistik entlasten, so dürfte die rein konjunkturelle Zunahme der Arbeitslosigkeit rund 300 000 betragen haben. Erst im nächsten Jahr ist eine leichte Besserung auf dem Arbeitsmarkt zu erwarten. Unter der Annahme, dass bis zum Jahresende 2006 etwa 300 000 Zusatzjobs geschaffen werden, dürfte sich die Zahl der registrierten Arbeitslosen in diesem Jahr auf 4,86 Millionen belauf

ifo Konjunkturprognose 2007/2008: Aufschwung mit niedrigerem Tempo

Die Weltwirtschaft befindet sich im vierten Jahr eines konjunkturellen Aufschwungs und expandierte auch im Frühjahr 2007 kräftig. Das Bruttoinlandsprodukt legte infolge der günstigen Ertragslage der Unternehmen, höherer Aktienkurse und der zwar zuletzt gestiegenen, aber immer noch vergleichsweise niedrigen langfristigen Zinsen dynamisch zu. Und auch im Prognosezeitraum wird die Expansion der Weltwirtschaft schwungvoll bleiben, sich jedoch etwas abflachen. In der Eurozone setzt sich der Aufschwung zunächst schwungvoll fort, verliert aber im nächsten Jahr etwas an Dynamik. In den Industrieländern wird das Bruttoinlandsprodukt im Jahr 2007 um 2,5% und im Jahr 2008 um 2,8% zunehmen. Der Welthandel wird in diesem Jahr um 7,5% und im nächsten Jahr um 8,0% expandieren. In Deutschland hat sich der Aufschwung nach der Jahreswende trotz der Erhöhung der Mehrwertsteuer fortgesetzt. Saisonbereinigt ist die gesamtwirtschaftliche Produktion im ersten Quartal mit einer laufenden Jahresrate von 2,1% gestiegen, zuvor hatte das Expansionstempo allerdings noch bei 4,0% gelegen. Im Prognosezeitraum dürfte sich der konjunkturelle Aufschwung fortsetzen, dabei aber nicht mehr die hohe Dynamik des vergangenen Jahres erreichen. Die gesamtwirtschaftliche Produktion wird im laufenden Jahr um 2,6% expandieren; arbeitstäglich bereinigt um 2,8%. Im Jahr 2008 tritt der konjunkturelle Aufschwung in seine Spätphase ein.Weltkonjunktur, Konjunkturprognose, Wirtschaftslage, Wirtschaftswachstum, Deutschland, Welt

Toxic Epidermal Necrolysis after Pemetrexed and Cisplatin for Non-Small Cell Lung Cancer in a Patient with Sharp Syndrome

Background: Pemetrexed is an antifolate drug approved for maintenance and second-line therapy, and, in combination with cisplatin, for first-line treatment of advanced nonsquamous non-small cell lung cancer. The side-effect profile includes fatigue, hematological and gastrointestinal toxicity, an increase in hepatic enzymes, sensory neuropathy, and pulmonary and cutaneous toxicity in various degrees. Case Report: We present the case of a 58-year-old woman with history of Sharp's syndrome and adenocarcinoma of the lung, who developed toxic epidermal necrolysis after the first cycle of pemetrexed, including erythema, bullae, extensive skin denudation, subsequent systemic inflammation and severe deterioration in general condition. The generalized skin lesions occurred primarily in the previous radiation field and responded to immunosuppressive treatment with prednisone. Conclusion: Although skin toxicity is a well-known side effect of pemetrexed, severe skin reactions after pemetrexed administration are rare. Caution should be applied in cases in which pemetrexed is given subsequent to radiation therapy, especially in patients with pre-existing skin diseases