Fast & Scalable I/O for Emulated HPUX

HPE has positioned containerized solution called c-UX (code named Kiran) which runs HPUX in emulated (Itanium hardware emulation on x86) mode as a futuristic solution for the margin rich UNIX business. The value of containerized HPUX is that it allows customers using legacy HPUX applications to continue running on x86 hardware. Significant effort has been expended to increase the effectiveness of hardware resource utilization on c-UX. The next step in fully optimizing I/O in c-UX environment is to provide truly scalable high-performance, by enabling a single I/O device to provide DMA for multiple VMs. This scalability challenge can be solved using Single Root I/O Virtualization (SR-IOV) technology, delivering near-native I/O performance for multiple c-UX instances, while also providing memory and traffic isolation for security and high availability, accelerating live migrations, and reducing the cost and complexity of I/O solutions. Network and Storage adapters from various vendors can be used to realize SR-IOV on c-UX, which otherwise was not possible on native HPUX due to hardware and firmware limitations. This paper talks about an innovative mechanism to enable SR-IOV on emulated HPUX OS using Virtual Function I/O framework (VFIO) available in Linux. Disclosed is an approach of achieving highly scalable performance in c-UX application by allowing the guest OS direct access to parts of the I/O subsystem of the host and handle various aspects of the communication like DMA and interrupts. It also throws light on the network I/O performance gains achieved using this method

Natural Terpenes Prevent Mitochondrial Dysfunction, Oxidative Stress and Release of Apoptotic Proteins during Nimesulide-Hepatotoxicity in Rats

Nimesulide, an anti-inflammatory and analgesic drug, is reported to cause severe hepatotoxicity. In this study, molecular mechanisms involved in deranged oxidant-antioxidant homeostasis and mitochondrial dysfunction during nimesulide-induced hepatotoxicity and its attenuation by plant derived terpenes, camphene and geraniol has been explored in male Sprague-Dawley rats. Hepatotoxicity due to nimesulide (80 mg/kg BW) was evident from elevated SGPT, SGOT, bilirubin and histo-pathological changes. Antioxidants and key redox enzymes (iNOS, mtNOS, Cu/Zn-SOD, Mn-SOD, GPx and GR) were altered significantly as assessed by their mRNA expression, Immunoblot analysis and enzyme activities. Redox imbalance along with oxidative stress was evident from decreased NAD(P)H and GSH (56% and 74% respectively; P<0.001), increased superoxide and secondary ROS/RNS generation along with oxidative damage to cellular macromolecules. Nimesulide reduced mitochondrial activity, depolarized mitochondria and caused membrane permeability transition (MPT) followed by release of apoptotic proteins (AIF; apoptosis inducing factor, EndoG; endonuclease G, and Cyto c; cytochrome c). It also significantly activated caspase-9 and caspase-3 and increased oxidative DNA damage (level of 8-Oxoguanine glycosylase; P<0.05). A combination of camphene and geraniol (CG; 1∶1), when pre-administered in rats (10 mg/kg BW), accorded protection against nimesulide hepatotoxicity in vivo, as evident from normalized serum biomarkers and histopathology. mRNA expression and activity of key antioxidant and redox enzymes along with oxidative stress were also normalized due to CG pre-treatment. Downstream effects like decreased mitochondrial swelling, inhibition in release of apoptotic proteins, prevention of mitochondrial depolarization along with reduction in oxidized NAD(P)H and increased mitochondrial electron flow further supported protective action of selected terpenes against nimesulide toxicity. Therefore CG, a combination of natural terpenes prevented nimesulide induced cellular damage and ensuing hepatotoxicity

Functional outcome following excision of a tumour and reconstruction of the distal radius

We retrospectively studied the functional and oncological results of 15 patients after reconstruction of the distal radius with osteoarticular allograft or non-vascularised fibular graft following wide excision of an aggressive benign or malignant tumour. Eight patients underwent osteoarticular allograft and seven patients had a non-vascularised autogenous fibular graft reconstruction. The average time for incorporation of the graft was 6 and 5 months in each reconstruction respectively. There was no tumour recurrence after follow up over 41.5–95.5 (average 60.5) months. All patients had good and excellent functional results. Three patients in the group reconstructed with osteoarticular allograft had plate loosening and graft fractures which were successfully treated subsequently

Mechanisms of drug-induced liver injury

The idiosyncratic nature and poor prognosis of drug-induced liver injury (DILI) make this type of reaction a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The key to predicting and preventing DILI is understanding the underlying mechanisms. DILI is initiated by direct hepatotoxic effects of a drug, or a reactive metabolite of a drug. Parenchymal cell injury induces activation of innate and/or adaptive immune cells, which, in turn, produce proinflammatory and tissue hepatotoxic mediators, and/or mount immune reactions against drug-associated antigens. Understanding the molecular and cellular elements associated with these pathways can help identify risk factors and may ultimately facilitate the development of strategies to predict and prevent DILI