Electronic and magnetic properties of substitutional Mn clusters in (Ga,Mn)As

The magnetization and hole distribution of Mn clusters in (Ga,Mn)As are investigated by all-electron total energy calculations using the projector augmented wave method within the density-functional formalism. It is found that the energetically most favorable clusters consist of Mn atoms surrounding one center As atom. As the Mn cluster grows the hole band at the Fermi level splits increasingly and the hole distribution gets increasingly localized at the center As atom. The hole distribution at large distances from the cluster does not depend significantly on the cluster size. As a consequence, the spin-flip energy differences of distant clusters are essentially independent of the cluster size. The Curie temperature $T_C$ is estimated directly from these spin-flip energies in the mean field approximation. When clusters are present estimated $T_C$ values are around 250 K independent of Mn concentration whereas for a uniform Mn distribution we estimate a $T_C$ of about 600 K.Comment: 7 pages, 5 figures, 2 tables; Revised manuscript 26. May 200

Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Advanced Non-Small Cell Lung Cancer after Neoadjuvant Therapy.

In recent years autophagy has attracted the attention of researchers from many medical fields, including cancer research, and certain anti-macroautophagy drugs in combination with cytotoxic or targeted therapies have entered clinical trials. In the present study, we focused on a less explored subtype of autophagy, i.e., chaperone-mediated autophagy (CMA), with the key proteins LAMP2A and HSPA8 (HSC70), and their immunohistochemical evaluation with previously extensively validated antibodies. We were interested in whether the marker expression is influenced by the antecedent therapy, and its correlation with survival on a cohort of patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and matched primary resected tumors. In concordance with our previous study, we did not find any intratumoral heterogeneity, nor correlation between the two parameters, nor correlation between the markers and any included pathological parameters. Surprisingly, the expression of both markers was also independent to tumor response or administered neoadjuvant treatment. In the survival analysis, the results were only significant for LAMP2A, where higher levels were associated with longer 5-year overall survival and disease-free survival for the mixed group of adenocarcinomas and squamous cell carcinomas (p < 0.0001 and p = 0.0019 respectively) as well as the squamous cell carcinoma subgroup (p = 0.0001 and p = 0.0001 respectively). LAMP2A was also an independent prognostic marker in univariate and multivariate analysis

Zukunftstrends im Tourismus

Trotz internationalem Terrorismus, extremen Wetterereignissen und wirtschaftlichen Krisensymptomen ist die Reiselust der Deutschen nicht nachhaltig beeinträchtigt. Das globale System Tourismus scheint sich – auch unter dem Einfluss von Strukturbrüchen und Krisen – flexibel an die Wirklichkeit der Risikogesellschaft zu adaptieren und wird seinem Ruf als Boombranche gerecht. Wie aber sieht die Zukunft des Tourismus aus? Kann er der Vision einer Leitökonomie des 21. Jahrhunderts auch weiterhin gerecht werden? Die Autoren skizzieren in diesem Band mögliche Entwicklungspfade und Zukünfte des Tourismus und erörtern hierauf bezogenen Forschungs- und Handlungsbedarf. Im Mittelpunkt stehen dabei drei thematische Felder von hoher Relevanz: Die Implikationen des soziodemografischen Wandels für den Tourismus; die Einflüsse, die von der EU-Erweiterung auf den Tourismus und die Strategien der Reiseanbieter ausgehen; sowie Fragen der Sicherheit – hier geht es u.a. um die Wahrnehmung und Kommunikation von Risiken mit ihren Auswirkungen für Reiseentscheidungen und um Konzepte der Krisenprävention und des Krisenmanagements auf Seiten der nationalen wie der internationalen Akteure

Potentiating vascular-targeted photodynamic therapy through CSF-1R modulation of myeloid cells in a preclinical model of prostate cancer

Vascular-targeted photodynamic therapy (VTP) induces rapid destruction of targeted tissues and is a promising therapy for prostate cancer. However, the resulting immune response, which may play an important role in either potentiating or blunting the effects of VTP, is still incompletely understood. Myeloid cells such as myeloid-derived suppressor cells (MDSCs) and macrophages are often found in tumors and are widely reported to be associated with cancer angiogenesis, tissue remodeling, and immunosuppression. These cells are also known to play a critical role in wound-healing, which is induced by rapid tissue destruction. In this study, we investigated the effects of VTP on the recruitment of tumor-infiltrating myeloid cells, specifically MDSCs and tumor-associated macrophages (TAMs), in the Myc-Cap and TRAMP C2 murine prostate cancer models. We report that VTP increased the infiltration of myeloid cells into the tumors, as well as their expression of CSF1R, a receptor required for myeloid differentiation, proliferation, and tumor migration. As anti-CSF1R treatment has previously been used to deplete these cells types in other murine models of prostate cancer, we hypothesized that combining anti-CSF1R with VTP therapy would lead to decreased tumor regrowth and improved survival. Importantly, we found that targeting myeloid cells using anti-CSF1R in combination with VTP therapy decreased the number of tumor MDSCs and TAMs, especially M2 macrophages, as well as increased CD8 T cell infiltration, decreased tumor growth and improved overall survival. These results suggest that targeting myeloid cells via CSF1R targeting is a promising strategy to potentiate the anti-tumor effects of VTP

E-Commerce in Deutschland : Eine kritische Bestandsaufnahme zum elektronischen Handel

Kann das Thema E-Commerce nicht ad acta gelegt werden, nachdem der Hype um die New Economy abgeklungen ist? Dieser Band zeigt, daß E-Commerce nichts von seiner enormen Bedeutung für die Modernisierung von Wirtschaft und Gesellschaft verloren hat und nach wie vor eine wichtige Herausforderung auch für die Politik darstellt. In vielen Bereichen ist der elektronische Handel bereits fest etabliert, und die dadurch mittel- und längerfristig ausgelösten Strukturveränderungen müssen bewältigt werden. Aber die Bedingungen für den elektronischen Handel unterscheiden sich grundlegend je nach Branche, Gütern, Akteuren und den ökonomischen und politischen Rahmenbedingungen. Dieser Erkenntnis folgend wurden acht Wirtschaftsbereiche für eine nähere Analyse ausgewählt, nämlich der Handel mit Lebensmitteln, Automobilen, Arzneimitteln, Medienprodukten (Buch, Tonträger, Video), Strom, Wertpapieren und Dienstleistungen sowie die Beschaffungsprozesse im öffentlichen Bereich. Ergänzt werden diese Detailuntersuchungen um Abschätzungen zu den Folgen des E-Commerce (z.B. Arbeitsmarkteffekte, verkehrliche und ökologische Folgen). Außerdem werden Handlungsfelder für Forschung und Politik benannt, die sich insbesondere an den Auftraggeber dieser Studie, den Deutschen Bundestag, richten

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis

A synthesis of atmospheric mercury depletion event chemistry in the atmosphere and snow

It was discovered in 1995 that, during the spring time, unexpectedly low concentrations of gaseous elemental mercury (GEM) occurred in the Arctic air. This was surprising for a pollutant known to have a long residence time in the atmosphere; however conditions appeared to exist in the Arctic that promoted this depletion of mercury (Hg). This phenomenon is termed atmospheric mercury depletion events (AMDEs) and its discovery has revolutionized our understanding of the cycling of Hg in Polar Regions while stimulating a significant amount of research to understand its impact to this fragile ecosystem. Shortly after the discovery was made in Canada, AMDEs were confirmed to occur throughout the Arctic, sub-Artic and Antarctic coasts. It is now known that, through a series of photochemically initiated reactions involving halogens, GEM is converted to a more reactive species and is subsequently associated to particles in the air and/or deposited to the polar environment. AMDEs are a means by which Hg is transferred from the atmosphere to the environment that was previously unknown. In this article we review Hg research taken place in Polar Regions pertaining to AMDEs, the methods used to collect Hg in different environmental media, research results of the current understanding of AMDEs from field, laboratory and modeling work, how Hg cycles around the environment after AMDEs, gaps in our current knowledge and the future impacts that AMDEs may have on polar environments. The research presented has shown that while considerable improvements in methodology to measure Hg have been made but the main limitation remains knowing the speciation of Hg in the various media. The processes that drive AMDEs and how they occur are discussed. As well, the role that the snow pack and the sea ice play in the cycling of Hg is presented. It has been found that deposition of Hg from AMDEs occurs at marine coasts and not far inland and that a fraction of the deposited Hg does not remain in the same form in the snow. Kinetic studies undertaken have demonstrated that bromine is the major oxidant depleting Hg in the atmosphere. Modeling results demonstrate that there is a significant deposition of Hg to Polar Regions as a result of AMDEs. Models have also shown that Hg is readily transported to the Arctic from source regions, at times during springtime when this environment is actively transforming Hg from the atmosphere to the snow and ice surfaces. The presence of significant amounts of methyl Hg in snow in the Arctic surrounding AMDEs is important because this species is the link between the environment and impacts to wildlife and humans. Further, much work on methylation and demethylation processes has occurred but these processes are not yet fully understood. Recent changes in the climate and sea ice cover in Polar Regions are likely to have strong effects on the cycling of Hg in this environment; however more research is needed to understand Hg processes in order to formulate meaningful predictions of these changes

MIR376A is a regulator of starvation-induced autophagy

Background: Autophagy is a vesicular trafficking process responsible for the degradation of long-lived, misfolded or abnormal proteins, as well as damaged or surplus organelles. Abnormalities of the autophagic activity may result in the accumulation of protein aggregates, organelle dysfunction, and autophagy disorders were associated with various diseases. Hence, mechanisms of autophagy regulation are under exploration. Methods: Over-expression of hsa-miR-376a1 (shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy-related targets of the miRNA were predicted using Microcosm Targets and MIRanda bioinformatics tools and experimentally validated. Endogenous miRNA was blocked using antagomirs and the effects on target expression and autophagy were analyzed. Luciferase tests were performed to confirm that 3’ UTR sequences in target genes were functional. Differential expression of MIR376A and the related MIR376B was compared using TaqMan quantitative PCR. Results: Here, we demonstrated that, a microRNA (miRNA) from the DlkI/Gtl2 gene cluster, MIR376A, played an important role in autophagy regulation. We showed that, amino acid and serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7 and Huh-7 cells. MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1). Indeed, 3’ UTR sequences in the mRNA of these autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir tests showed that, endogenous MIR376A was participating to the control of ATG4C and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A accelerated starvation-induced autophagic activity. Interestingly, MIR376A and MIR376B levels were increased with different kinetics in response to starvation stress and tissue-specific level differences were also observed, pointing out to an overlapping but miRNA-specific biological role. Conclusions: Our findings underline the importance of miRNAs encoded by the DlkI/Gtl2 gene cluster in stress-response control mechanisms, and introduce MIR376A as a new regulator of autophagy