The influence of land cover roughness on the results of high resolution tsunami inundation modeling

In this paper a local case study is presented in which detailed inundation simulations have been performed to support damage analysis and risk assessment related to the 2004 tsunami in Phang Nga and Phuket, Thailand. Besides tsunami sources, bathymetry and topography, bottom roughness induced by vegetation and built environment is considered to influence inundation characteristics, such as water depths or flow velocities and therefore attracts major attention in this work. Plenty of information available on the 2004 tsunami event, high-resolution satellite imagery and extensive field measurements to derive land cover information and forest stand parameters facilitated the generation of topographic datasets, land cover maps and site-specific Manning values for the most prominent land cover classes in the study areas. The numerical models ComMIT and Mike 21 FM were used to hindcast the observed tsunami inundation and to draw conclusions on the influence of land cover on inundation patterns. Results show a strong influence of dense vegetation on flow velocities, which were reduced by up to 50% by mangroves, while the inundation extent is influenced only to a lesser extent. In urban areas, the disregard of buildings in the model led to a significant overestimation of the inundation extent. Hence different approaches to consider buildings were used and analyzed in the model. The case study highlights the importance and quantifies the effects of considering land cover roughness in inundation simulations used for local risk assessment

To Kick Against the Pricks: An Examination of the Oresteia and the Acts of the Apostles

The major themes found in the Oresteia and the books of Luke and Acts of the Apostles are compared. By focusing on the similarities found in the themes of Justice, Religion, and New versus Old, the reader may determine if the phrase in question is being used as a literary allusion in the book of Acts of the Apostles to the Oresteia trilogy. The author believes this to be the case and believes that to arrive at a full understanding of the literary meaning of the phrase in question, an understanding of the major themes of the Oresteia is necessary

phase i ii first in human trial with m7583 a bruton s tyrosine kinase inhibitor btki in patients with b cell malignancies

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Thermoelectric properties of lead chalcogenide core-shell nanostructures

We present the full thermoelectric characterization of nanostructured bulk PbTe and PbTe-PbSe samples fabricated from colloidal core-shell nanoparticles followed by spark plasma sintering. An unusually large thermopower is found in both materials, and the possibility of energy filtering as opposed to grain boundary scattering as an explanation is discussed. A decreased Debye temperature and an increased molar specific heat are in accordance with recent predictions for nanostructured materials. On the basis of these results we propose suitable core-shell material combinations for future thermoelectric materials of large electric conductivities in combination with an increased thermopower by energy filtering.Comment: 12 pages, 8 figure

Clinical response to Auron Misheil Therapy in a man with advanced multifocal hepatocellular carcinoma: A case report

<p>Abstract</p> <p>Introduction</p> <p>Auron Misheil Therapy was developed based on similarities between carcinogenesis and inflammation. Auron Misheil Therapy is a combination of natural and synthetic compounds, including anti-inflammatory drugs and insulin, expected to exhibit synergistic effects.</p> <p>Case presentation</p> <p>Here, we report the case of a 78-year-old Caucasian male patient who presented with multifocal hepatocellular carcinoma and chronic hepatitis C virus infection. Over a four-year period our patient was treated with radiofrequency ablation and transarterial chemoembolization. After these treatments there was tumor progression, with new hyperperfused lesions without evidence of extrahepatic tumor involvement. Our patient refused sorafenib therapy. Therefore, he received twice daily intramuscular injections of Auron Misheil Therapy on an outpatient basis for two months. Partial remission of the hepatic lesions was observed eight weeks after the start of treatment, and confirmed four weeks later. Unfortunately, at that time our patient refused therapy due to dizziness. During follow-up two target lesions remained stable, but one lesion increased in size. At the latest follow-up, one year later, there was still tumor control.</p> <p>Conclusion</p> <p>While the mechanisms underlying the antitumor effects of Auron Misheil Therapy are not fully understood, stable disease and remissions have been observed in different types of tumors, including hepatocellular carcinoma.</p

Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity

<p>Abstract</p> <p>Background</p> <p>Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling networks.</p> <p>Results</p> <p>Here we present evidence for such a scenario, involving retrogenes of Rap1 belonging to the Ras family of small GTPases. We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins. Markedly, human hRap1B-retro and mouse mRap1A-retro1 acquired mutations in the 12^thand 59^thamino acids, respectively, corresponding to residues mutated in constitutively active oncogenic Ras proteins. Statistical and structural analyses support a functional evolution scenario, where Rap1 isoforms of retrogenic origin are functionally distinct from their parental proteins. Indeed, all retrogene-encoded GTPases have an increased GTP/GDP binding ratio <it>in vivo</it>, indicating that their conformations resemble that of active GTP-bound Rap1. We furthermore demonstrate that these three Rap1 isoforms exhibit distinct affinities for the Ras-binding domain of RalGDS. Finally, when tested for their capacity to induce key cellular processes like integrin-mediated cell adhesion or cell spreading, marked differences are seen.</p> <p>Conclusions</p> <p>Together, these data lend strong support for an evolution scenario, where retrotransposition and subsequent mutation events generated species-specific Rap1 isoforms with differential signaling potential. Expression of the constitutively active human Rap1B-retro in cells like those derived from Ramos Burkitt's lymphoma and bone marrow from a patient with myelodysplastic syndrome (MDS) warrants further investigation into its role in disease development.</p

Determination of Ras-GTP and Ras-GDP in patients with acute myelogenous leukemia (AML), myeloproliferative syndrome (MPS), juvenile myelomonocytic leukemia (JMML), acute lymphocytic leukemia (ALL), and malignant lymphoma: assessment of mutational and indirect activation

The 21-kD protein Ras of the low-molecular-weight GTP-binding (LMWG) family plays an important role in transduction of extracellular signals. Ras functions as a ‘molecular switch’ in transduction of signals from the membrane receptors of many growth factors, cytokines, and other second messengers to the cell nucleus. Numerous studies have shown that in multiple malignant tumors and hematopoietic malignancies, faulty signal transduction via the Ras pathway plays a key role in tumorigenesis. In this work, a non-radioactive assay was used to quantify Ras activity in hematologic malignancies. Ras activation was measured in six different cell lines and 24 patient samples, and sequence analysis of N- and K-ras was performed. The 24 patient samples comprised of seven acute myelogenous leukemia (AML) samples, five acute lymphocytic leukemia (ALL) samples, four myeloproliferative disease (MPD) samples, four lymphoma samples, four juvenile myelomonocytic leukemia (JMML) samples, and WBC from a healthy donor. The purpose of this study was to compare Ras activity determined by percentage of Ras-GTP with the mutational status of the Ras gene in the hematopoietic cells of the patients. Mutation analysis revealed ras mutations in two of the seven AML samples, one in codon 12 and one in codon 61; ras mutations were also found in two of the four JMML samples, and in one of the four lymphoma samples (codon 12). We found a mean Ras activation of 23.1% in cell lines with known constitutively activating ras mutations, which was significantly different from cell lines with ras wildtype sequence (Ras activation of 4.8%). Two of the five activating ras mutations in the patient samples correlated with increased Ras activation. In the other three samples, Ras was probably activated through “upstream” or “downstream” mechanisms

Cell-Free Synthesis of the Mitochondrial ADP/ATP Carrier Protein of Neurospora crassa

ADP/ATP carrier protein was synthesized in heterologous cell-free systems programmed with Neurospora poly(A)-containing RNA and homologous cell-free systems from Neurospora. The apparent molecular weight of the product obtained in vitro was the same as that of the authentic mitochondrial protein. The primary translation product obtained in reticulocyte lysates starts with formylmethionine when formylated initiator methionyl-tRNA (fMet-tRNAfMet) was present. The product synthesized in vitro was released from the ribosomes into the postribosomal supernatant. The evidence presented indicates that the ADP/ATP carrier is synthesized as a polypeptide with the same molecular weight as the mature monomeric protein and does not carry an additional sequence

Dysregulation of a novel miR-23b/27b-p53 axis impairs muscle stem cell differentiation of humans with type 2 diabetes

Objective: MicroRNAs (miRNAs) are increasingly recognized as fine-tuning regulators of metabolism, and are dysregulated in several disease conditions. With their capacity to rapidly change gene expression, miRNAs are also important regulators of development and cell differentiation. In the current study, we describe an impaired myogenic capacity of muscle stem cells isolated from humans with type 2 diabetes (T2DM) and assess whether this phenotype is regulated by miRNAs. Methods: We measured global miRNA expression during in vitro differentiation of muscle stem cells derived from T2DM patients and healthy controls. Results: The mir-23b/27b cluster was downregulated in the cells of the patients, and a pro-myogenic effect of these miRNAs was mediated through the p53 pathway, which was concordantly dysregulated in the muscle cells derived from humans with T2DM. Conclusions: Our results indicate that we have identified a novel pathway for coordination of myogenesis, the miR-23b/27b-p53 axis that, when dysregulated, potentially contributes to a sustained muscular dysfunction in T2DM