On formal specification of emergent behaviours in swarm robotic systems

It is a characteristic of swarm robotics that specifying overall emergent swarm behaviours in terms of the low-level behaviours of individual robots is very difficult. Yet if swarm robotics is to make the transition from the laboratory to real-world engineering realisation we need such specifications. This paper explores the use of temporal logic to formally specify, and possibly also prove, the emergent behaviours of a robotic swarm. The paper makes use of a simplified wireless connected swarm as a case study with which to illustrate the approach. Such a formal approach could be an important step toward a disciplined design methodology for swarm robotics

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals

Background. At present, it is difficult to visualize the internalization of surface receptors induced by ubiquitination that is taken place at the plasma membrane in mammals. This problem makes it difficult to reveal molecular basis for ubiquitinationmediated internalization in mammals. Methodology/Principle Findings. In order to overcome it, we have generated T-REx-c-MIR, a novel mammalian Tet-on B cell line using a constitutively active E3 ubiquitin ligase, c-MIR, and its artificial target molecule. By applying the surface biotinylation method to T-REx-c-MIR, we succeeded to monitor the fate of surface target molecules after initiation of ubiquitination process by doxycycline (Dox)-induced c-MIR expression. Target molecules that preexisted at the plasma membrane before induction of c-MIR expression were oligo-ubiquitinated and degraded by Dox-induced c-MIR expression. Dox-induced c-MIR expression initiated rapid internalization of surface target molecules, and blockage of the internalization induced the accumulation of the surface target molecules that were newly ubiquitinated by c-MIR. Inhibition of the surface ubiquitination by down-regulating ubiquitin conjugating enzyme E2 impaired the internalization of target molecules. Finally, a complex of c-MIR and target molecule was detected at the plasma membrane. Conclusions/ Significances. These results demonstrate that in T-REx-c-MIR, surface target molecule is ubiquitinated at the plasma membrane and followed by being internalized from the plasma membrane. Thus, T-REx-c-MIR is a useful experimental tool t

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98–1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03–1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00–2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16–2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07–1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted

High maternal mortality estimated by the sisterhood method in a rural area of Mali

<p>Abstract</p> <p>Background</p> <p>Maternal mortality is high in Mali. Nevertheless, there are few studies on this topic from rural areas, and current estimates are mostly based on studies from urban settings. Our objective was to estimate the maternal mortality ratio in Kita, rural Mali.</p> <p>Methods</p> <p>Using the "sisterhood method", we interviewed participants aged 15-50 years from 20 villages in Kita, Mali, and thereby created a retrospective cohort of their sisters in reproductive age. Based on population and fertility estimates, we calculated the lifetime risk of maternal death, and from that the estimated approximate maternal mortality ratio.</p> <p>Results</p> <p>The 2,039 respondents reported 4,628 sisters who had reached reproductive age. Of these 4,628 sisters, almost a third (1,233; 27%) had died, and 429 (9%) had died during pregnancy or childbirth. This corresponded to a lifetime risk of maternal death of 20% and a maternal mortality ratio of 3,131 per 100,000 live births (95% confidence interval 2,967-3,296), with a time reference around 1999.</p> <p>Conclusions</p> <p>We found a very high maternal mortality in rural Mali and this highlights the urgent need for obstetric services in the remote rural areas.</p

Evaluation of an influenza-like illness case definition in the diagnosis of influenza among patients with acute febrile illness in cambodia

<p>Abstract</p> <p>Background</p> <p>Influenza-like illness (ILI) is often defined as fever (>38.0°C) with cough or sore throat. In this study, we tested the sensitivity, specificity, and positive and negative predictive values of this case definition in a Cambodia patient population.</p> <p>Methods</p> <p>Passive clinic-based surveillance was established at nine healthcare centers to identify the causes of acute undifferentiated fever in patients aged two years and older seeking treatment. Fever was defined as tympanic membrane temperature >38°C lasting more than 24 hours and less than 10 days. Influenza virus infections were identified by polymerase chain reaction.</p> <p>Results</p> <p>From July 2008 to December 2008, 2,639 patients were enrolled. From 884 (33%) patients positive for influenza, 652 presented with ILI and 232 acute fever patients presented without ILI. Analysis by age group identified no significant differences between influenza positive patients from the two groups. Positive predictive values (PPVs) varied during the course of the influenza season and among age groups.</p> <p>Conclusion</p> <p>The ILI case definition can be used to identify a significant percentage of patients with influenza infection during the influenza season in Cambodia, assisting healthcare providers in its diagnosis and treatment. However, testing samples based on the criteria of fever alone increased our case detection by 34%.</p

Structure of a ubiquitin-loaded HECT ligase reveals the molecular basis for catalytic priming

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Role of prothrombotic polymorphisms in successful or unsuccessful aging

The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor V polymorphism (G1691A), and G20210A of prothrombin (FII) in three cohorts of subjects: patients with Alzheimer\u2019s disease (unsuccessful aging), nonagenarians (successful aging) and young healthy controls, to assess whether allelic variants associated to the modification of haemostatic system function, may play a role in the protection or susceptibility to Alzheimer disease, as well as to reach a successful aging. No significant differences were observed in the frequencies of the three groups studied. These results indicate that the presence or absence of the gene variants examined did not influence the achievement of advanced age and are not risk factors for Alzheimer\u2019s disease. The state of hypercoagulability and the possession of these risk alleles appear to be compatible with the achievement of longevity and are not implied as risk factors in Alzheimer disease development