Adapting a HEP Application for Running on the Grid

The goal of the EU IST int.eu.grid project is to build middleware facilities which enable the execution of real-time and interactive applications on the Grid. Within this research, relevant support for the HEP application is provided by Virtual Organization, monitoring system, and real-time dispatcher (RTD). These facilities realize the pilot jobs idea that allows to allocate grid resources in advance and to analyze events in real time. In the paper we present HEP Virtual Organization, the details of monitoring, and RTD. We present the way of running the HEP application using the above facilities to fit into the real-time application requirements

THE ATLAS EXPERIMENT ON-LINE MONITORING AND FILTERING AS AN EXAMPLE OF REAL-TIME APPLICATION

The ATLAS detector, recording LHC particles’ interactions, produces events with rate of40 MHz and size of 1.6 MB. The processes with new and interesting physics phenomena arevery rare, thus an efficient on-line filtering system (trigger) is necessary. The asynchronouspart of that system relays on few thousands of computing nodes running the filtering software.Applying refined filtering criteria results in increase of processing times what may lead tolack of processing resources installed on CERN site. We propose extension to this part ofthe system based on submission of the real-time filtering tasks into the Grid

Immunohistochemical expression of mitochondrial membrane complexes (MMCs) I, III, IV and V in malignant and benign periampullary epithelium: a potential target for drug therapy of periampullary cancer?

<p>Abstract</p> <p>Background</p> <p>Mitochondrial membrane complexes (MMCs) are key mediators of cellular oxidative phosphorylation, and inhibiting them could lead to cell death. No published data are available on the relative abundance of MMCs in different periampullary cancers. Therefore, we studied the expression profile of MMCs I, III, IV and V in periampullary cancers, reactive pancreatitis, normal pancreas and chronic pancreatitis.</p> <p>Methods</p> <p>This was a retrospective study on tissue microarrays constructed from formalin-fixed paraffin-embedded tissue from 126 consecutive patients (cancer = 104, chronic pancreatitis = 22) undergoing pancreatic resections between June 2001 and June 2006. 78 specimens of chronic pancreatitis tissue were obtained adjacent to areas of cancer. Normal pancreatic tissue was obtained from the resection specimens in a total of 30 patients. Metastatic tumours in 61 regional lymph nodes from 61 patients were also studied.</p> <p>Results</p> <p>MMCs I, III, IV and V were highly expressed (p < 0.05) in all primary periampullary cancers compared with metastatic lymph nodes and adjacent benign pancreas. MMCs III, IV and V were highly expressed in all cancers regardless of type compared with chronic pancreatitis (p < 0.05). Higher expression of MMCs I and V was associated with better survival and may, in part, relate to lower expression of these MMCs in poorly differentiated tumours compared with well and moderately differentiated tumours.</p> <p>Conclusions</p> <p>Differential expression of MMCs III, IV and V in primary periampullary cancers compared with adjacent benign periampullary tissue and chronic pancreatitis is a novel finding, which may render them attractive anticancer targets.</p

Impaired Mitochondrial Respiratory Functions and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks). These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I) and succinate:ubiquinone oxidoreductase (Complex II) were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications

Hydrogen Peroxide Acts on Sensitive Mitochondrial Proteins to Induce Death of a Fungal Pathogen Revealed by Proteomic Analysis

How the host cells of plants and animals protect themselves against fungal invasion is a biologically interesting and economically important problem. Here we investigate the mechanistic process that leads to death of Penicillium expansum, a widespread phytopathogenic fungus, by identifying the cellular compounds affected by hydrogen peroxide (H2O2) that is frequently produced as a response of the host cells. We show that plasma membrane damage was not the main reason for H2O2-induced death of the fungal pathogen. Proteomic analysis of the changes of total cellular proteins in P. expansum showed that a large proportion of the differentially expressed proteins appeared to be of mitochondrial origin, implying that mitochondria may be involved in this process. We then performed mitochondrial sub-proteomic analysis to seek the H2O2-sensitive proteins in P. expansum. A set of mitochondrial proteins were identified, including respiratory chain complexes I and III, F1F0 ATP synthase, and mitochondrial phosphate carrier protein. The functions of several proteins were further investigated to determine their effects on the H2O2-induced fungal death. Through fluorescent co-localization and the use of specific inhibitor, we provide evidence that complex III of the mitochondrial respiratory chain contributes to ROS generation in fungal mitochondria under H2O2 stress. The undesirable accumulation of ROS caused oxidative damage of mitochondrial proteins and led to the collapse of mitochondrial membrane potential. Meanwhile, we demonstrate that ATP synthase is involved in the response of fungal pathogen to oxidative stress, because inhibition of ATP synthase by oligomycin decreases survival. Our data suggest that mitochondrial impairment due to functional alteration of oxidative stress-sensitive proteins is associated with fungal death caused by H2O2

Mitochondrial targeted catalase suppresses invasive breast cancer in mice

<p>Abstract</p> <p>Background</p> <p>Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential.</p> <p>Methods</p> <p>Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined.</p> <p>Results</p> <p>PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm²/cm²of lung tissue compared with 1.3 mm²/cm²of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects.</p> <p>Conclusion</p> <p>Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer.</p> <p>Please see related commentary article: <url>http://www.biomedcentral.com/1741-7015/9/62</url></p

Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

Hypoxia-inducible factor (HIF) is a nuclear transcription factor that responds to environmental and pathological hypoxia to induce metabolic adaptation, vascular growth, and cell survival. Here we found that HIF subunits and HIF2α in particular were normally expressed in the mediobasal hypothalamus of mice. Hypothalamic HIF was up-regulated by glucose to mediate the feeding control of hypothalamic glucose sensing. Two underlying molecular pathways were identified, including suppression of PHDs by glucose metabolites to prevent HIF2α degradation and the recruitment of AMPK and mTOR/S6K to regulate HIF2α protein synthesis. HIF activation was found to directly control the transcription of POMC gene. Genetic approach was then employed to develop conditional knockout mice with HIF inhibition in POMC neurons, revealing that HIF loss-of-function in POMC neurons impaired hypothalamic glucose sensing and caused energy imbalance to promote obesity development. The metabolic effects of HIF in hypothalamic POMC neurons were independent of leptin signaling or pituitary ACTH pathway. Hypothalamic gene delivery of HIF counteracted overeating and obesity under conditions of nutritional excess. In conclusion, HIF controls hypothalamic POMC gene to direct the central nutrient sensing in regulation of energy and body weight balance

Hypoxia-inducible Factor-1 Activation in Nonhypoxic Conditions: The Essential Role of Mitochondrial-derived Reactive Oxygen Species

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor for responses to low oxygen. Here we report that the generation of mitochondrial reactive oxygen species are essential for regulating HIF-1 in normal oxygen conditions in the vasculature

The taper of cast post preparation measured using innovative image processing technique

<p>Abstract</p> <p>Background</p> <p>No documentation in the literature about taper of cast posts. This study was conducted to measure the degree of cast posts taper, and to evaluate its suitability based on the anatomy aspects of the common candidate teeth for post reconstruction.</p> <p>Methods</p> <p>Working casts for cast posts, prepared using Gates Glidden drills, were collected. Impressions of post spaces were made using polyvinyl siloxan putty/wash technique. Digital camera with a 10' high quality lens was used for capturing two digital images for each impression; one in the Facio-Lingual (FL) and the other in the Mesio-Distal (MD) directions. Automated image processing program was developed to measure the degree of canal taper. Data were analyzed using Statistical Package for Social Sciences software and One way Analysis of Variance.</p> <p>Results</p> <p>Eighty four dies for cast posts were collected: 16 for each maxillary anterior teeth subgroup, and 18 for each maxillary and mandibular premolar subgroup. Mean of total taper for all preparations was 10.7 degree. There were no statistical differences among the total taper of all groups (P = .256) or between the MD and FL taper for each subgroup. Mean FL taper for the maxillary first premolars was lower significantly (P = .003) than the maxillary FL taper of the second premolars. FL taper was higher than the MD taper in all teeth except the maxillary first premolars.</p> <p>Conclusions</p> <p>Taper produced did not reflect the differences among the anatomy of teeth. While this technique deemed satisfactory in the maxillary anterior teeth, the same could not be said for the maxillary first premolars. Careful attention to the root anatomy is mandatory.</p