Little Boxes: A Dynamic Optimization Approach for Enhanced Cloud Infrastructures

The increasing demand for diverse, mobile applications with various degrees of Quality of Service requirements meets the increasing elasticity of on-demand resource provisioning in virtualized cloud computing infrastructures. This paper provides a dynamic optimization approach for enhanced cloud infrastructures, based on the concept of cloudlets, which are located at hotspot areas throughout a metropolitan area. In conjunction, we consider classical remote data centers that are rigid with respect to QoS but provide nearly abundant computation resources. Given fluctuating user demands, we optimize the cloudlet placement over a finite time horizon from a cloud infrastructure provider's perspective. By the means of a custom tailed heuristic approach, we are able to reduce the computational effort compared to the exact approach by at least three orders of magnitude, while maintaining a high solution quality with a moderate cost increase of 5.8% or less

M+D: conceptual guidelines for compiling a materials library

This article proposes to present a study conducted by the Raw Materials research group, the results of which comprise the conceptual guidelines for compiling an M+D material library. The study includes the topic, materials and design taking the impact of the changes that came into being in the post industrial era on project methodologies and the search for information regarding materials. Taking into account the importance and complexity that these relationships have taken on currently, we have studied the issue of materials based on Manzini (1983) and Ashby and Johnson (2002). Afterward different databases and materials libraries located in the Brazil, the United States, France and Italy geared toward design professionals and students were analyzed to understand what information and means of access to them were available. The project methodologies were approached based on Löbach (1991), Bürdeck (1994), Schulmann (1994), Baxter (1998), Dantas (1998 and 2005) and Papanek (1995 and 2000). This study sought to identify the key elements of the role of materials in the project process today, to serve as a parameter for the analysis of the models studied. A comparative analysis of the models investigated enabled identification of positive and negative aspects to adapt to the needs previously mentioned and identify conceptual guidelines for compiling a collection of materials for use in design projects. Keywords: Design, Materials, Project Methodology, Library</p

Exploring societal solidarity in the context of extreme prematurity

QUESTION: Extreme prematurity can result in long-term disabilities. Its impact on society is often not taken into account and deemed controversial. Our study examined attitudes of the Swiss population regarding extreme prematurity and people’s perspectives regarding the question of solidarity with disabled people. METHODS: We conducted a nationwide representative anonymous telephone survey with 1210 Swiss residents aged 18 years or older. We asked how people estimate their own personal solidarity, the solidarity of their social environment and the solidarity across the country with disabled persons. Spearman’s correlation calculations were used to assess if a correlation exists between solidarity and setting financial limits to intensive care and between solidarity and withholding neonatal intensive care. RESULTS: According to 36.0% of the respondents intensive medical care should not be withheld from extremely preterm infants, even if their chances for an acceptable quality of life were poor. For 28.8%, intensive care should be withheld from these infants, and 26.9% held an intermediate position depending on the situation. A total of 31.5% were against setting a financial limit to treatment of extremely preterm newborns with an uncertain future quality of life, 34.2% were in favour and 26.9% were deliberating. A majority (88.8%) considered their solidarity toward disabled people as substantial; the solidarity of their personal environment and of the society at large was estimated as high by 79.1% and 48.6%, respectively. CONCLUSIONS: The Swiss population expressed a high level of solidarity which may alleviate some pressure on parents and health care providers in the decision-making process in neonatal intensive care units. In addition, there was no relationship between solidarity and people’s willingness to pay for the care or withholding treatment of extremely preterm babies

Leukemia Gene Atlas – A Public Platform for Integrative Exploration of Genome-Wide Molecular Data

Leukemias are exceptionally well studied at the molecular level and a wealth of high-throughput data has been published. But further utilization of these data by researchers is severely hampered by the lack of accessible integrative tools for viewing and analysis. We developed the Leukemia Gene Atlas (LGA) as a public platform designed to support research and analysis of diverse genomic data published in the field of leukemia. With respect to leukemia research, the LGA is a unique resource with comprehensive search and browse functions. It provides extensive analysis and visualization tools for various types of molecular data. Currently, its database contains data from more than 5,800 leukemia and hematopoiesis samples generated by microarray gene expression, DNA methylation, SNP and next generation sequencing analyses. The LGA allows easy retrieval of large published data sets and thus helps to avoid redundant investigations. It is accessible at www.leukemia-gene-atlas.org

Heterogeneous in vitro effects of doxorubicin on gene expression in primary human liposarcoma cultures

<p>Abstract</p> <p>Background</p> <p>Doxorubicin is considered one of the most potent established chemotherapeutics in the treatment of liposarcoma; however, the response rates usually below 30%, are still disappointing. This study was performed to identify gene expression changes in liposarcoma after doxorubicin treatment.</p> <p>Methods</p> <p>Cells of 19 primary human liposarcoma were harvested intraoperatively and brought into cell culture. Cells were incubated with doxorubicin for 24 h, RNA was isolated and differential gene expression was analysed by the microarray technique.</p> <p>Results</p> <p>A variety of genes involved in apoptosis were up and down regulated in different samples revealing a heterogeneous expression pattern of the 19 primary tumor cell cultures in response to doxorubicin treatment. However, more than 50% of the samples showed up-regulation of pro-apoptotic genes such as <it>TRAIL Receptor2</it>, <it>CDKN1A</it>, <it>GADD45A</it>, <it>FAS</it>, <it>CD40</it>, <it>PAWR</it>, <it>NFKBIA</it>, <it>IER3</it>, <it>PSEN1</it>, <it>RIPK2</it>, and <it>CD44</it>. The anti-apoptotic genes <it>TNFAIP3</it>, <it>PEA15</it>, <it>Bcl2A1</it>, <it>NGFB</it>, and <it>BIRC3 </it>were also up-regulated. The pro-apoptotic <it>CD14</it>, <it>TIA1</it>, and <it>ITGB2 </it>were down-regulated in more than 50% of the tumor cultures after treatment with doxorubicin, as was the antiapoptotic <it>YWHAH</it>.</p> <p>Conclusion</p> <p>Despite a correlation of the number of differentially regulated genes to the tumor grading and to a lesser extent histological subtype, the expression patterns varied strongly; however, especially among high grade tumors the responses of selected apoptosis genes were similar. The predescribed low clinical response rates of low grade liposarcoma to doxorubicin correspond to our results with only little changes on gene expression level and also divergent findings concerning the up- and down-regulation of single genes in the different sarcoma samples.</p

Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.</p

TRAIL and Taurolidine induce apoptosis and decrease proliferation in human fibrosarcoma

<p>Abstract</p> <p>Background</p> <p>Disseminated soft tissue sarcoma still represents a therapeutic dilemma because effective cytostatics are missing. Therefore we tested TRAIL and Tarolidine (TRD), two substances with apoptogenic properties on human fibrosarcoma (HT1080).</p> <p>Methods</p> <p>Viability, apoptosis and necrosis were visualized by TUNEL-Assay and quantitated by FACS analysis (Propidiumiodide/AnnexinV staining). Gene expression was analysed by RNA-Microarray and the results validated for selected genes by rtPCR. Protein level changes were documented by Western Blot analysis. NFKB activity was analysed by ELISA and proliferation assays (BrdU) were performed.</p> <p>Results and discussion</p> <p>The single substances TRAIL and TRD induced apoptotic cell death and decreased proliferation in HT1080 cells significantly. Gene expression of several genes related to apoptotic pathways (TRAIL: <it>ARHGDIA</it>, <it>NFKBIA</it>, <it>TNFAIP3</it>; TRD: <it>HSPA1A/B</it>, <it>NFKBIA</it>, <it>GADD45A</it>, <it>SGK</it>, <it>JUN</it>, <it>MAP3K14</it>) was changed. The combination of TRD and TRAIL significantly increased apoptotic cell death compared to the single substances and lead to expression changes in a variety of genes (<it>HSPA1A/B</it>, <it>NFKBIA</it>, <it>PPP1R15A</it>, <it>GADD45A</it>, <it>AXL</it>, <it>SGK</it>, <it>DUSP1</it>, <it>JUN</it>, <it>IRF1</it>, <it>MYC</it>, <it>BAG5</it>, <it>BIRC3</it>). NFKB activity assay revealed an antipodal regulation of the several subunits of NFKB by TRD and TRD+TRAIL compared to TRAIL alone.</p> <p>Conclusion</p> <p>TRD and TRAIL are effective to induce apoptosis and decrease proliferation in human fibrosarcoma. A variety of genes seems to be involved, pointing to the NFKB pathway as key regulator in TRD/TRAIL-mediated apoptosis.</p

Bone drilling with fiber guided excimer laser beam

Zur Ermittlung einer optimalen Parametereinstellung des Excimerlasers für die Bearbeitung von Knochengewebe, testeten wir bei drei unterschiedlichen Impulslängen den Einfluß von Austrittsenergie und Repetitionsrate auf die Ablationstiefe.An experiment is presented which shows the relationship between energy, repetition rate and pulse width to the bone ablation rate using a fiber guided excimer laser beam

Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer’s disease brain

Background Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer’s disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden have both been associated with neurodegenerative diseases and cognitive decline. This study aims to systematically identify which common brain pathologies in the aged human brain are associated with mitochondrial recalibrations and to disentangle the relationship between these pathologies, mtDNAcn, mtDNA heteroplasmy, aging, neuronal loss, and cognitive function. Methods Whole-genome sequencing data from n = 1361 human brain samples from 5 different regions were used to quantify mtDNAcn as well as heteroplasmic mtDNA point mutations and small indels. Brain samples were assessed for 10 common pathologies. Annual cognitive test results were used to assess cognitive function proximal to death. For a subset of samples, neuronal proportions were estimated from RNA-seq profiles, and mass spectrometry was used to quantify the mitochondrial protein content of the tissue. Results mtDNAcn was 7–14% lower in AD relative to control participants. When accounting for all 10 common neuropathologies, only tau was significantly associated with lower mtDNAcn in the dorsolateral prefrontal cortex. In the posterior cingulate cortex, TDP-43 pathology demonstrated a distinct association with mtDNAcn. No changes were observed in the cerebellum, which is affected late by pathologies. Neither age nor gender was associated with mtDNAcn in the studied brain regions when adjusting for pathologies. Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. In contrast, mtDNA heteroplasmy levels increased by 1.5% per year of life in the cortical regions, but displayed no association with any of the pathologies or cognitive function. Conclusions We studied mtDNA quantity and quality in relation to mixed pathologies of aging and showed that tau and not amyloid-β is primarily associated with reduced mtDNAcn. In the posterior cingulate cortex, the association of TDP-43 with low mtDNAcn points to a vulnerability of this region in limbic-predominant age-related TDP-43 encephalopathy. While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases