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HEARTS OF DARKNESS

MALAÏSE France

LIVE! LIVE! LIVE!VEN.02 JUIN à METZ, La Chaouée w/ TOTAL VICTORY + OROMOCTO DIAMONDTO ... CATCH A THIEF: www.youtube.com/watch?v=mN72W7Xo9eA Live Göteborg, Sweden: www.youtube.com/watch?v=YyX1lhVo6Kc ... more more

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"We believe we have defenses to the claims and will respond accordingly," GE said.

Alstom corruption case: GE acquired Alstom's power business in 2015, a deal that has backfired by increasing its exposure to slumping coal. GE faces legal proceedings related to alleged anti-competitive conduct and improper payments by Alstom linked to projects in Israel and Slovenia.

Alstom corruption case:

The Alstom conduct in question took place before GE bought the business. GE has set aside $858 million for potential losses here, but it has warned that the losses could be higher.

Offshore wind turbines : GE said it is still cooperating with a European Commission investigation into the company's proposed takeover of LM Wind, a Danish maker of rotor blades. Regulators have alleged that during a review of the deal, GE provided incorrect or misleading information about its offshore wind turbine research and development activities. GE faces a fine up to 1% of its annual revenue, or about $1.2 billion, if the EC finds the violations were intentional or negligent.

Offshore wind turbines

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Dr. Bassin joined the faculty of Department of Emergency Medicine in 2009 after completing residency training at the University of Cincinnati where he served as Chief Resident. His academic interests include improving the quality, delivery and standardization of care to critically ill patients, advanced airway interventions, and the development of computerized clinical decision support tools. Additionally, he has a focus on LEAN healthcare facility design and utilizing process improvement and workflow optimization to maximize effectiveness of the built environment. He was an integral member of the planning, design and implementation team for the first ED ICU in the country, the U-M Emergency Critical Care Center (EC3). He is one of less than 10 physicians in the country to hold the Evidenced-Based Design Accreditation and Certification (EDAC) from the Center for Healthcare Design and currently is on the Lean Facility Design Steering Committee for the new Clinical Inpatient Tower at UMHS. He currently serves as the Director of Critical Care Operations, the Associate Medical Director for Critical Care Transport and the Associate Service Chief for the Department of Emergency Medicine. In these roles, he has an established track record of administrative leadership in process improvement, optimization of the delivery of ED-based critical care, quality assurance, risk mitigation, and throughput optimization utilizing lean-based strategies.

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Aberrant energy metabolism represents a hallmark of cancer and contributes to numerous aggressive behaviors of cancer cells, including cell death and survival. Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable development of drug resistance, metabolic reprograming of MCL cells remains an unexplored area. Posttranslational modification of proteins via O- GlcNAcylation is an ideal sensor for nutritional changes mediated by O -GlcNAc transferase (OGT) and is removed by O -GlcNAcase (OGA). Using various small-molecule inhibitors of OGT and OGA, we found for the first time that O- GlcNAcylation potentiates MCL response to bortezomib. CRISPR interference of MGEA5 (encoding OGA) validated the apoptosis sensitization by O- GlcNAcylation and OGA inhibition. To identify the potential clinical candidates, we tested MCL response to drug-like OGA inhibitor, ketoconazole, and verified that it exerts similar sensitizing effect on bortezomib-induced apoptosis. Investigations into the underlying molecular mechanisms reveal that bortezomib and ketoconazole act in concert to cause the accumulation of truncated Bid (tBid). Not only does ketoconazole potentiate tBid induction, but also increases tBid stability through O- GlcNAcylation that interferes with tBid ubiquitination and proteasomal degradation. Remarkably, ketoconazole strongly enhances bortezomib-induced apoptosis in de novo bortezomib-resistant MCL cells and in patient-derived primary cells with minimal cytotoxic effect on normal peripheral blood mononuclear cells and hepatocytes, suggesting its potential utility as a safe and effective adjuvant for MCL. Together, our findings provide novel evidence that combination of bortezomib and ketoconazole or other OGA inhibitors may present a promising strategy for the treatment of drug-resistant MCL. Mol Cancer Ther; 17(2); 484–96. ©2017 AACR .

Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

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