From “business as usual” to sustainable “purpose‐driven business”: Challenges facing the purpose ecosystem in the United Kingdom and Australia

Purpose‐driven businesses have a stated objective to contribute to the welfare of society and the planet alongside generating shareholder value. As interest in purpose‐driven businesses grows, an emerging “purpose ecosystem” of advisers, investors, and enablers offers different types of support for businesses wanting to transition to sustainability. This paper examines how the transition towards purpose‐driven business in Australia and the United Kingdom requires addressing challenges facing this support ecosystem at three levels. First, at the individual level where support providers need to build the capabilities of managers who are experiencing tensions around integrating societal and environmental purpose while facing pressure for maximizing shareholder value. Second, the support providers working within the purpose ecosystem offering professional advice and finance face their own tensions between environmental or social objectives and commercial pressures. Third, there are challenges facing actors in the ecosystems aiming to change the wider policy and institutional environment but facing lobbying from those wanting to keep “business as usual.” We identify practical implications for those parts of the purpose‐driven business ecosystem providing support. This includes building capabilities to combine social, environmental, and commercial purpose; coordination among support providers; and creating an institutional environment to avoid “purpose wash.

Tsunami 2004

The Tsunami after the sea quake in Southeast Asia at the 26th of December 2004 represents one of the largest disasters in the modern World. Approximately 228,000 people from the countries surrounding the Indian Ocean have died. A large number of visitors from different European countries staying for their Christmas holidays in Thailand and Sri Lanka became victims of the natural disaster. The large number of foreign victims in these countries required additional forensic investigations which were organized by internationally working DVI (Disaster Victim Identification) teams. Victim identification was a great challenge due to the environmental conditions rapidly leading to heavily decomposed bodies. Thus the forensic medical investigations were very important to identify the victims. The different steps of forensic medical, odonto-stomatological and molecular genetic investigations beginning at the end of 2004 with the identification of a small number of victims and ending with the closing of the TTVI IMC (Thai Tsunami Victim Identification Information Management Center) in Phuket one year later are described and critically discussed. Up to 31 international DVI Teams worked in the TTVI IMC during 2005

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma

BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored. METHODS: We performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties of MACC1 overexpressing GBM cells. We quantified MACC1 dependent dynamics of 3D aggregate formation. For mechanistic studies we measured the expression of key adhesion molecules using qRT-PCR, and MACC1 dependent changes in short term adhesion to fibronectin and laminin. We then determined changes in sub-cellular distribution of integrins and actin in dependence of MACC1, but also in microtubule and intermediate filament organization. RESULTS: MACC1 increased the migratory speed and elastic modulus of GBM cells, but decreased cell-cell adhesion and inhibited the formation of 3D aggregates. These effects were not associated with altered mRNA expression of several key adhesion molecules or altered short-term affinity to laminin and fibronectin. MACC1 did neither change the organization of the microtubule nor intermediate filament cytoskeleton, but resulted in increased amounts of protrusive actin on laminin. CONCLUSION: MACC1 overexpression increases elastic modulus and migration and reduces adhesion of GBM cells thereby impeding 3D aggregate formation. The underlying molecular mechanism is independent on the organization of microtubules, intermediate filaments and several key adhesion molecules, but depends on adhesion to laminin. Thus, targeting re-organization of the cytoskeleton and cell motility via MACC1 may offer a treatment option to impede GBM spreading

Les reseaux hvdc multi-terminaux: des defies multipes en genie electrique high voltage direct current grid multiterminals: many challenges in electrical engineering

Electrical installation using high voltage need to be improve to make the exchanges of power under the sea with security and to connect the offshore sources. Alterative grid show limits in those applications. High voltage direct current (HVDC) installation can be a solution to those cases, if some technological and scientist problem are solved. Challenge are in every level of the electrical engineering work, in the whole system, with the material used, and the way their used. This article introduce the main challenges in the domain of electrical engineering to solve in case of the exploitation of a HVDC grid

Conceptual Design for Electromagnetic Guided Rotary Table in Machine Tools

Difficult-to-machine materials are still challenging the production industry. Examples are highly complex components of aircraft engines. Alongside innovative processes, also improved machine tool components are helping to comply with the demands of this task. This paper presents a design approach of a rotary table with an active magnetic bearing. Opportunities in machining through employing magnetic guides are presented and discussed in the beginning. In the following, a workflow for the magnetic bearing design in swivel rotary tables is proposed. The mentioned steps are executed based on a presently under design rotary table

Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freibur

MACC1-induced collective migration is promoted by proliferation rather than single cell biomechanics

Metastasis-associated in colon cancer 1 (MACC1) is a marker for metastasis, tumor cell migration, and increased proliferation in colorectal cancer (CRC). Tumors with high MACC1 expression show a worse prognosis and higher invasion into neighboring structures. Yet, many facets of the pro-migratory effects are not fully understood. Atomic force microscopy and single cell live imaging were used to quantify biomechanical and migratory properties in low- and high-MACC1-expressing CRC cells. Furthermore, collective migration and expansion of small, cohesive cell colonies were analyzed using live cell imaging and particle image velocimetry. Lastly, the impact of proliferation on collective migration was determined by inhibition of proliferation using mitomycin. MACC1 did not affect elasticity, cortex tension, and single cell migration of CRC cells but promoted collective migration and colony expansion in vitro. Measurements of the local velocities in the dense cell layers revealed proliferation events as regions of high local speeds. Inhibition of proliferation via mitomycin abrogated the MACC1-associated effects on the collective migration speeds. A simple simulation revealed that the expansion of cell clusters without proliferation appeared to be determined mostly by single cell properties. MACC1 overexpression does not influence single cell biomechanics and migration but only collective migration in a proliferation-dependent manner. Thus, targeting proliferation in high-MACC1-expressing tumors may offer additional effects on cell migration

The Impact of Starvation on the Microbiome and Gut-Brain Interaction in Anorexia Nervosa

Interactions between the gut microbiome and the brain are of increasing interest to both researchers and clinicians. Evidence is mounting on the causal role of an altered gut microbiome in inflammatory diseases such as arthritis, inflammatory bowel disease, obesity and diabetes, and psychiatric diseases like anxiety and depression. Mechanisms include altered energy harvest from food, hormonal changes, increased gut permeability, inflammation, immune response, and a direct influence on the brain and behavior. Anorexia nervosa (AN) is the third most common disease in adolescence and exacts a high burden on patients and caregivers. It often becomes chronic and has the highest mortality of all psychiatric diseases. As AN is characterized by nutritional restrictions, weight loss, and severe behavioral symptoms including weight phobia, comorbid anxiety and depression, accompanied by endocrine alterations, increased inflammation, and immune response, exploring the role of the gut microbiome is crucial. Here, we present an overview of the potential mechanisms of interaction between the gut microbiome, the host and particularly the brain in AN and summarize the initial findings of microbiome research on AN. We conclude by identifying future research directions and potential therapeutic approaches, including nutritional interventions, probiotics, prebiotics and food supplements, that could become important additions to current AN therapy

Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker

BACKGROUND: The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression. METHODS: MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan-Meier analyses. RESULTS: Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival. CONCLUSIONS: We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P