Siemens Jobs -UAE

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Purchasing ﹠ Supply Chain Manager - Energy Solar ﹠ Hydro Req ID 99722 - Posted 22/02/2012 - UAE  -  Dubai  -  Energy Sector SCM-Procurement/Logistics  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Executive Assistant Req ID 99510 - Posted 22/02/2012 - UAE  -  Dubai  -  Energy Sector Administration & Support  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
Senior Engineer - Substation Control ﹠ Monitoring Req ID 99486 - Posted 20/02/2012 - UAE  -  Abu Dhabi  -  Energy Sector Engineering  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Senior Engineer - Gas Insulated Switchgears Req ID 99489 - Posted 20/02/2012 - UAE  -  Dubai  -  Energy Sector Engineering  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Senior Engineer - Control ﹠ Protection (Gas Insulated Switchgears) Req ID 99490 - Posted 20/02/2012 - UAE  -  Dubai  -  Energy Sector Engineering  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Engineer - Substation Control ﹠ Monitoring Req ID 99491 - Posted 20/02/2012 - UAE  -  Dubai  -  Energy Sector Engineering  -  Early professional (1 - 3 years)  -  Permanent  -  Full time only	Select Action
Engineer - Control ﹠ Protection (Gas INsulated Switchgears) Req ID 99492 - Posted 20/02/2012 - UAE  -  Dubai  -  Energy Sector Engineering  -  Early professional (1 - 3 years)  -  Permanent  -  Full time only	Select Action
Head of ME Cluster Executive Office Req ID 99169 - Posted 15/02/2012 - UAE  -  Dubai  -  Regional Clusters Strategy  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Focus Account Manager Req ID 98153 - Posted 07/02/2012 - UAE  -  Industry Sector Sales  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Buyer Req ID 98152 - Posted 07/02/2012 - UAE  -  Corporate Units SCM-Procurement/Logistics  -  Early professional (1 - 3 years)  -  Limited  -  Full time only	Select Action

Lead Protection Engineer - Smart Grid Energy Automation Req ID 97258 - Posted 31/01/2012 - UAE  -  Abu Dhabi  -  Infrastructure and Cities Sector Engineering  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Head of HR Services - Lower Gulf Region Req ID 97252 - Posted 31/01/2012 - UAE  -  Jebel Ali  -  Corporate Units Human Resources  -  Experienced professional (10+ years)  -  Permanent  -  Full time only	Select Action
Auditor - Operational Practice Req ID 96453 - Posted 23/01/2012 - UAE  -  Dubai  -  Regional Clusters Audit  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
Auditor - Financial Practice Req ID 96452 - Posted 23/01/2012 - UAE  -  Dubai  -  Regional Clusters Audit  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
Siemens Graduate Program - UAE Req ID 95861 - Posted 18/01/2012 - UAE  -  Cross-Sector Businesses Administration & Support  -  Early professional (1 - 3 years)  -  Limited  -  Full time only	Select Action
Commercial Officer Req ID 95610 - Posted 17/01/2012 - UAE  -  Infrastructure and Cities Sector Finance  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
Paralegal Req ID 95658 - Posted 16/01/2012 - UAE  -  Corporate Units Legal & Compliance  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
Senior Legal Counsel Req ID 94377 - Posted 05/01/2012 - UAE  -  Dubai  -  Corporate Units Legal & Compliance  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only	Select Action
General Bid Manager (Energy Fossil) Req ID 41511 - Posted 03/01/2012 - UAE  -  Dubai  -  Energy Sector General Management  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Oil ﹠ Gas Development Manager (Vertical Market Management) Req ID 93646 - Posted 22/12/2011 - UAE  -  Industry Sector Sales  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action  Technical Manager - Fire Safety Systems Req ID 92222 - Posted 12/12/2011 - UAE  -  Infrastructure and Cities Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Sales Engineer - BMS ﹠ HVAC Systems Req ID 75936 - Posted 30/11/2011 - UAE  -  Abu Dhabi  -  Infrastructure and Cities Sector Sales  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Supply Chain Manager - Methods, Processes ﹠ Tools Req ID 74135 - Posted 24/11/2011 - UAE  -  Dubai  -  Corporate Units SCM-Procurement/Logistics  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action  Supply Chain Category Manager - Mobility Req ID 87468 - Posted 24/11/2011 - UAE  -  Dubai  -  Corporate Units SCM-Procurement/Logistics  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Service Manager - Building Technologies Req ID 83226 - Posted 24/11/2011 - UAE  -  Dubai  -  Infrastructure and Cities Sector Customer Services/Services  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Senior Technical Support Engineer (Fire Safety ﹠ Security) Req ID 74244 - Posted 24/11/2011 - UAE  -  Dubai  -  Infrastructure and Cities Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Senior Sales Engineer - BMS ﹠ HVAC Systems Req ID 75939 - Posted 24/11/2011 - UAE  -  Abu Dhabi  -  Infrastructure and Cities Sector Sales  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Senior Field Service Technician (CCTV) Req ID 87385 - Posted 24/11/2011 - UAE  -  Infrastructure and Cities Sector Customer Services/Services  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  SCADA Design/Estimation Engineer Req ID 75135 - Posted 24/11/2011 - UAE  -  Abu Dhabi  -  Industry Sector Sales  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Sales Engineers ﹠ Sales Managers Req ID 74754 - Posted 24/11/2011 - UAE  -  Dubai  -  Industry Sector Sales  -  Not defined  -  Permanent  -  Full time only Select Action  Sales Engineer - Low Voltage Systems Req ID 68475 - Posted 24/11/2011 - UAE  -  Dubai  -  Infrastructure and Cities Sector Sales  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Sales Account Manager - Process Analytics Req ID 32194 - Posted 24/11/2011 - UAE  -  Dubai  -  Industry Sector Sales  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Quality Controller Req ID 81479 - Posted 24/11/2011 - UAE  -  Dubai  -  Corporate Units Quality  -  Early professional (1 - 3 years)  -  Permanent  -  Full time only Select Action  Project Manager (m/f) I﹠C for Power Plant in Iraq and Middle East Req ID 84589 - Posted 24/11/2011 - UAE  -  Energy Sector PM@Siemens  -  Mid-level professional (>3 years)  -  N/A (imported)  -  Full time only Select Action  Project Engineers ﹠ Project Managers Req ID 74755 - Posted 24/11/2011 - UAE  -  Dubai  -  Industry Sector Engineering  -  Not defined  -  Permanent  -  Full time only Select Action  Pre Sales Petrochemical / Oil ﹠ Gas Engineer Req ID 38838 - Posted 24/11/2011 - UAE  -  Dubai  -  Industry Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Legal Secretary Req ID 26983 - Posted 24/11/2011 - UAE  -  Dubai  -  Corporate Units Administration & Support  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Lead Engineer - Automation Req ID 69737 - Posted 24/11/2011 - UAE  -  Abu Dhabi  -  Industry Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Lead Engineer (Gas Turbine ﹠ Steam Turbine Generator Sets) Req ID 38233 - Posted 24/11/2011 - UAE  -  Dubai  -  Energy Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Head of Expert House - Industry Customer Service Division Req ID 90083 - Posted 24/11/2011 - UAE  -  Industry Sector Customer Services/Services  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action  Field Service Technicians (HVAC ﹠ BMS) Req ID 76698 - Posted 24/11/2011 - UAE  -  Dubai  -  Infrastructure and Cities Sector Engineering  -  Early professional (1 - 3 years)  -  Permanent  -  Full time only Select Action  Field Service Technician - Fire ﹠ Security Req ID 85296 - Posted 24/11/2011 - UAE  -  Infrastructure and Cities Sector Customer Services/Services  -  Early professional (1 - 3 years)  -  Permanent  -  Full time only Select Action  Field Service Engineers ﹠ Senior Field Service Engineers Req ID 74750 - Posted 24/11/2011 - UAE  -  Dubai  -  Industry Sector Engineering  -  Not defined  -  Permanent  -  Full time only Select Action  Field Service Engineer Req ID 73760 - Posted 24/11/2011 - UAE  -  Dubai  -  Energy Sector Engineering  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Commodity Manager (Fleet, Marketing ﹠ Communications) Req ID 87471 - Posted 24/11/2011 - UAE  -  Corporate Units SCM-Procurement/Logistics  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Commodity Manager Req ID 87367 - Posted 24/11/2011 - UAE  -  Abu Dhabi  -  Energy Sector SCM-Procurement/Logistics  -  Mid-level professional (>3 years)  -  Permanent  -  Full time only Select Action  Business Development Manager - Ultrasound Req ID 70670 - Posted 24/11/2011 - UAE  -  Dubai  -  Healthcare Sector General Management  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action  Head of Service Delivery - Industry Customer Service Division Req ID 90085 - Posted 23/11/2011 - UAE  -  Industry Sector Customer Services/Services  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action  Head of Sales ﹠ Marketing - Industry Customer Service Division Req ID 90084 - Posted 23/11/2011 - UAE  -  Industry Sector Sales  -  Experienced professional (10+ years)  -  Permanent  -  Full time only Select Action

How chemotherapy becomes more effective

 by Biomechanism 

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Researchers from the University of Zurich have found a cellular brake that protects cancer cells from chemotherapy – and they demonstrate which medication can be used to render it inoperative.

Their study published in the journal “Natural Structural and Molecular Biology” provides the molecular basis for promising therapeutic advances.

Although many cancer drugs have already been in use for decades, their mode of action is still unknown. The new research results now challenge a mechanism of action that was previously proposed for a group of drugs and supported with experiments: the Topoisomerase I-inhibitor Camptothecin (Top1 inhibitor for short) and its derivatives used in chemotherapy, Topotecan and Irinotecan. Continue reading below…

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Problem: emergency cellular brake restricts effectiveness

In untreated cells, each parental DNA strand (P) is duplicated to form two identical daughter strands (T) by standard, three-pronged replication forks (black arrow). Upon treatment with top1 inhibitors, a fourth reversed arm (U) forms on the replication forks (red arrow). This molecular mechanism temporarily halts the replication process and protects the cancer cell from the cytotoxic effect of the drug.– (These pictures were taken with an electron microscope with a magnification of 46,000x. Copyright: UZH).

For a long time, the toxicity of the top1-inhibitors was attributed to discontinuities in the cancer cells’ DNA that inevitably caused breaks in the chromosomes during the duplication of the DNA.

The team headed by Professor Massimo Lopes at the University of Zurich’s Institute of Molecular Cancer Research has now identified a mechanism with which cancer cells protect themselves against damage caused by Top1 inhibitions: Using electron microscopy, the researchers were able to demonstrate that Top1 inhibitors can cause the replication forks that develop during the duplication of the DNA to be restructured. “Reversed” replication forks, or “chicken-foot” structures as they are also known, are formed.

This remodeling of the replication forks provides the cancer cells with the time they need to repair the lesion in the DNA and thus prevent disparately cytotoxic chromosomal breakage.

“Until now, the assumed mechanism of action of Top1 inhibitors was comparable to a train hurtling towards an obstacle without brakes that inevitably ends up derailing,” explains Massimo Lopes, commenting on the results. “What we have now discovered is the emergency brake, which the cells activate themselves to protect themselves from the inhibitor.” Arnab Ray-Chaudhuri, who made a considerable contribution to the study, draws the following conclusion: “Thanks to the discovery of this mechanism, we now understand why chemotherapy does not always work as expected with these drugs.”

The existence of such DNA structures was hypothesized many years ago, but it has only just been confirmed in human cells by Lopes’s group. These chicken-foot structures are even surprisingly common with clinically relevant doses of Top1 inhibitors.

Solution: render emergency brake inoperative

The new observations reveal an interesting coincidence: In pulling the emergency brake, a family of enzymes that recently attracted a great deal of interest as a potential target for new cancer therapies is involved in the restructuring: the poly-ADP-ribose polymerases, or PARPS for short. After all, PARP inhibitors increase the sensitivity of cancer cells to different drugs that harm the DNA, including Top1 inhibitors. The new study reveals why: PARP inhibition hinders the reversal of the replication forks and increases the number of chromosomal breaks caused by Top1 inhibitors. Massimo Lopes and his team thus provide a clear molecular basis for the clinical observations described and pave the way for promising therapeutic advances.

Massimo Lopes’s team is currently investigating whether the same or a similar mechanism is activated by other classes of chemotherapeutics and which cellular factors are involved in this molecular “emergency brake”. The aim is to identify tumors in which this mechanism is not active or inhibit the mechanism pharmacologically to improve the efficacy of chemotherapy.

Literature:

A. Ray Chaudhuri, Y. Hashimoto, R. Herrador, K.J. Neelsen, D. Fachinetti, R. Bermejo, A. Cocito, V. Costanzo and M. Lopes. Toposiomerase I poisoning results in PARP-mediated replication fork reversal. Nature Structural and Molecular Biology. 4 March, 2012. Doi: 10.1038/nsmb.2258

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Courtesy University of Zurich

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