12 resultados para LKM


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A routing protocol in a mobile ad hoc network (MANET) should be secure against both the outside attackers which do not hold valid security credentials and the inside attackers which are the compromised nodes in the network. The outside attackers can be prevented with the help of an efficient key management protocol and cryptography. However, to prevent inside attackers, it should be accompanied with an intrusion detection system (IDS). In this paper, we propose a novel secure routing with an integrated localized key management (SR-LKM) protocol, which is aimed to prevent both inside and outside attackers. The localized key management mechanism is not dependent on any routing protocol. Thus, unlike many other existing schemes, the protocol does not suffer from the key management - secure routing interdependency problem. The key management mechanism is lightweight as it optimizes the use of public key cryptography with the help of a novel neighbor based handshaking and Least Common Multiple (LCM) based broadcast key distribution mechanism. The protocol is storage scalable and its efficiency is confirmed by the results obtained from simulation experiments.

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Redd counting is an integral part of most Fishery Officers duties. The number and distribution of salmonid redds throughout salmonid catchments provides invaluable information on the range and extent of spawning by both salmon and sea trout. A project was initiated by the Fisheries Science and Management Team of Central Area, North West Region in England in liaison with the Flood Defence function. The main objective of this project was to assess redd count data for Central Area and attempt to quantify these data in order to produce a grading system that would highlight key salmonid spawning areas. By showing which were the main areas for salmon and sea trout spawning, better informed decisions could be made on whether or not in-stream Flood Defence works should be given the go-ahead. The main salmonid catchments in Central Area were broken into individual reaches, approximately 1 km in length. The number of redds in these individual reaches were then calculated and a density per lkm value was obtained for each reach. A grading system was devised which involved looking at the range of density per km values and dividing this by five to produce 5 classes, A - E. A sixth class (F) was used where the density per Ion value was 0.00. This grading system was calculated at two levels of detail. Grades for salmon and sea trout were produced for each individual catchment and also on an Area-wide level. Maps were produced using a range of colours to represent the grade for each reach. These maps provide a highly useful overview of the status of salmonid spawning for each catchment over individual years and highlight the key salmon and sea trout spawning areas in each catchment. These maps and the associated summary data should now provide Flood Defence and Fisheries staff with a fairly detailed overview of the status of spawning in any location within the. main salmonid catchments in Central Area. Although these maps are very useful they should only be used as a guide. The current practice of consulting with the local Fishery Officer should be continued to ensure that expert local knowledge is taken into account.

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The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment. (c) 2012 Wiley Periodicals, Inc.

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Liver kidney microsomal type 1 (LKM-1) antibodies have been shown to decrease the CYP2D6 activity in vitro and are present in a minority of patients with chronic hepatitis C infection. We investigated whether LKM-1 antibodies might reduce the CYP2D6 activity in vivo. All patients enrolled in the Swiss Hepatitis C Cohort Study and tested for LKM-1 antibodies were assessed (n = 1723): 10 eligible patients were matched with patients without LKM-1 antibodies. Patients were genotyped for CYP2D6 variants to exclude individuals with a poor metabolizer genotype. CYP2D6 activity was measured by a specific substrate using the dextromethorphan/dextrorphan metabolic ratio to classify patients into four activity phenotypes. All patients had a CYP2D6 extensive metabolizer genotype. The observed phenotype was concordant with the CYP2D6 genotype in most LKM-negative patients, whereas only three LKM-1 positive patients had a concordant phenotype (six presented an intermediate and one a poor metabolizer phenotype). The median DEM/DOR ratio was sixfold higher in LKM-1 positive than in LKM-1 negative patients (0.096 vs. 0.016, P = 0.004), indicating that CYP2D6 metabolic function was significantly reduced in the presence of LKM-1 antibodies. In chronic hepatitis C patients with LKM-1 antibodies, the CYP2D6 metabolic activity was on average reduced by 80%. The impact of LKM-1 antibodies on CYP2D6-mediated drug metabolism pathways warrants further translational studies.

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Pancreatic cancer is the 4th most common cause for cancer death in the United States, accompanied by less than 5% five-year survival rate based on current treatments, particularly because it is usually detected at a late stage. Identifying a high-risk population to launch an effective preventive strategy and intervention to control this highly lethal disease is desperately needed. The genetic etiology of pancreatic cancer has not been well profiled. We hypothesized that unidentified genetic variants by previous genome-wide association study (GWAS) for pancreatic cancer, due to stringent statistical threshold or missing interaction analysis, may be unveiled using alternative approaches. To achieve this aim, we explored genetic susceptibility to pancreatic cancer in terms of marginal associations of pathway and genes, as well as their interactions with risk factors. We conducted pathway- and gene-based analysis using GWAS data from 3141 pancreatic cancer patients and 3367 controls with European ancestry. Using the gene set ridge regression in association studies (GRASS) method, we analyzed 197 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Using the logistic kernel machine (LKM) test, we analyzed 17906 genes defined by University of California Santa Cruz (UCSC) database. Using the likelihood ratio test (LRT) in a logistic regression model, we analyzed 177 pathways and 17906 genes for interactions with risk factors in 2028 pancreatic cancer patients and 2109 controls with European ancestry. After adjusting for multiple comparisons, six pathways were marginally associated with risk of pancreatic cancer ( P < 0.00025): Fc epsilon RI signaling, maturity onset diabetes of the young, neuroactive ligand-receptor interaction, long-term depression (Ps < 0.0002), and the olfactory transduction and vascular smooth muscle contraction pathways (P = 0.0002; Nine genes were marginally associated with pancreatic cancer risk (P < 2.62 × 10−5), including five reported genes (ABO, HNF1A, CLPTM1L, SHH and MYC), as well as four novel genes (OR13C4, OR 13C3, KCNA6 and HNF4 G); three pathways significantly interacted with risk factors on modifying the risk of pancreatic cancer (P < 2.82 × 10−4): chemokine signaling pathway with obesity ( P < 1.43 × 10−4), calcium signaling pathway (P < 2.27 × 10−4) and MAPK signaling pathway with diabetes (P < 2.77 × 10−4). However, none of the 17906 genes tested for interactions survived the multiple comparisons corrections. In summary, our current GWAS study unveiled unidentified genetic susceptibility to pancreatic cancer using alternative methods. These novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer, once confirmed, will shed promising light on the prevention and treatment of this disease. ^

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Mode of access: Internet.

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Pennsylvania Department of Transportation, Bureau of Materials, Testing and Research, Harrisburg

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Pennsylvania Department of Transportation, Harrisburg

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Federal Highway Administration, Washington, D.C.