Influence of Morphological Changes in a Source Material on the Growth Interface of 4H-SiC Single Crystals

In this study, the change of mass distribution in a source material is tracked using an in situ computer tomography (CT) setup during the bulk growth of 4H- silicon carbide (SiC) via physical vapor depostion (PVT). The changing properties of the source material due to recrystallization and densification are evaluated. Laser flash measurement showed that the thermal properties of different regions of the source material change significantly before and after the growth run. The Si-depleted area at the bottom of the crucible is thermally insulating, while the residual SiC source showed increased thermal conductivity compared to the initially charged powder. Ex situ CT measurements revealed a needle-like structure with elongated pores causing anisotropic behavior for the heat conductivity. Models to assess the thermal conductivity are applied in order to calculate the changes in the temperature field in the crucible and the changes in growth kinetics are discussed

Asymptotically cylindrical 7-manifolds of holonomy G_2 with applications to compact irreducible G_2-manifolds

We construct examples of exponentially asymptotically cylindrical Riemannian 7-manifolds with holonomy group equal to G_2. To our knowledge, these are the first such examples. We also obtain exponentially asymptotically cylindrical coassociative calibrated submanifolds. Finally, we apply our results to show that one of the compact G_2-manifolds constructed by Joyce by desingularisation of a flat orbifold T^7/\Gamma can be deformed to one of the compact G_2-manifolds obtainable as a generalized connected sum of two exponentially asymptotically cylindrical SU(3)-manifolds via the method given by the first author (math.DG/0012189).Comment: 36 pages; v2: corrected trivial typos; v3: some arguments corrected and improved; v4: a number of improvements on presentation, paritularly in sections 4 and 6, including an added picture

Homage to Professor INUZUKA Susumu

千葉大学「人文研究」第41

Dung‐visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate

Dung beetles are important actors in the self‐regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space‐for‐time approach to test the effects of land use and climate on α‐diversity, local community specialization (H (2)′) on dung resources, and γ‐diversity of dung‐visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land‐use types: forests, grasslands, arable sites, and settlements, embedded in near‐natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung‐visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ‐diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung‐visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ‐diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung‐visiting beetle diversity and alter community networks. A decrease in dung‐visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage

On the origin of European sheep as revealed by the diversity of the Balkan breeds and by optimizing population-genetic analysis tools

Background: In the Neolithic, domestic sheep migrated into Europe and subsequently spread in westerly and northwesterly directions. Reconstruction of these migrations and subsequent genetic events requires a more detailed characterization of the current phylogeographic differentiation. Results: We collected 50 K single nucleotide polymorphism (SNP) profiles of Balkan sheep that are currently found near the major Neolithic point of entry into Europe, and combined these data with published genotypes from southwest-Asian, Mediterranean, central-European and north-European sheep and from Asian and European mouflons. We detected clines, ancestral components and admixture by using variants of common analysis tools: geography-informative supervised principal component analysis (PCA), breed-specific admixture analysis, across-breed f 4 profiles and phylogenetic analysis of regional pools of breeds. The regional Balkan sheep populations exhibit considerable genetic overlap, but are clearly distinct from the breeds in surrounding regions. The Asian mouflon did not influence the differentiation of the European domestic sheep and is only distantly related to present-day sheep, including those from Iran where the mouflons were sampled. We demonstrate the occurrence, from southeast to northwest Europe, of a continuously increasing ancestral component of up to 20% contributed by the European mouflon, which is assumed to descend from the original Neolithic domesticates. The overall patterns indicate that the Balkan region and Italy served as post-domestication migration hubs, from which wool sheep reached Spain and north Italy with subsequent migrations northwards. The documented dispersal of Tarentine wool sheep during the Roman period may have been part of this process. Our results also reproduce the documented 18th century admixture of Spanish Merino sheep into several central-European breeds. Conclusions: Our results contribute to a better understanding of the events that have created the present diversity pattern, which is relevant for the management of the genetic resources represented by the European sheep population

Nilotinib and Imatinib Are Comparably Effective in Reducing Growth of Human Eosinophil Leukemia Cells in a Newly Established Xenograft Model

We developed a xenograft model of human Chronic Eosinophilic Leukemia (CEL) to study disease progression and remission-induction under therapy with tyrosine kinase inhibitors using imatinib and nilotinib as examples. The FIP1L1/PDGFRA+ human CEL cell lineEOL-1 was injected intravenously into scid mice, and MR imaging and FACS analysis of mouse blood samples were performed to monitor disease development and the effects of imatinib and nilotinib. Organ infiltration was analyzed in detail by immunohistochemistry after sacrifice. All animals developed CEL and within one week of therapy, complete remissions were seen with both imatinib and nilotinib, resulting in reduced total tumor volumes by MR-imaging and almost complete disappearance of EOL-1 cells in the peripheral blood and in tissues. The new model system is feasible for the evaluation of new tyrosine kinase inhibitors and our data suggest that nilotinib may be a valuable additional targeted drug active in patients with FIP1L1/PDGFRA+ CEL

The importance of nerve microenvironment for schwannoma development

Schwannomas are predominantly benign nerve sheath neoplasms caused by Nf2 gene inactivation. Presently, treatment options are mainly limited to surgical tumor resection due to the lack of effective pharmacological drugs. Although the mechanistic understanding of Nf2 gene function has advanced, it has so far been primarily restricted to Schwann cell-intrinsic events. Extracellular cues determining Schwann cell behavior with regard to schwannoma development remain unknown. Here we show pro-tumourigenic microenvironmental effects on Schwann cells where an altered axonal microenvironment in cooperation with injury signals contribute to a persistent regenerative Schwann cell response promoting schwannoma development. Specifically in genetically engineered mice following crush injuries on sciatic nerves, we found macroscopic nerve swellings in mice with homozygous nf2 gene deletion in Schwann cells and in animals with heterozygous nf2 knockout in both Schwann cells and axons. However, patient-mimicking schwannomas could only be provoked in animals with combined heterozygous nf2 knockout in Schwann cells and axons. We identified a severe re-myelination defect and sustained macrophage presence in the tumor tissue as major abnormalities. Strikingly, treatment of tumor-developing mice after nerve crush injury with medium-dose aspirin significantly decreased schwannoma progression in this disease model. Our results suggest a multifactorial concept for schwannoma formation-emphasizing axonal factors and mechanical nerve irritation as predilection site for schwannoma development. Furthermore, we provide evidence supporting the potential efficacy of anti-inflammatory drugs in the treatment of schwannomas

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation