Unusual Behaviour of an Earth-Rockhill Dam

The post-construction behaviour of a 47.5 m high and 700 m long earth-rockfill dam, located in northwestern Iran, is described. The embankment dam is founded on Tertiary rock on both abutments, but in the river channel it rests on alluvial deposits of variable composition and thickness. Since the first impoundment, the dam has undergone large deformations, both in vertical and in horizontal directions. These have resulted in unusual differential settlements, visible along the crest, and have produced wide longitudinal cracks in the asphalt pavement of the crest road. The principle features of the dam are described and selected monitoring results of the crest movements for a sixteen year period are presented. Based on the analysis of the available data and taking into account the geotechnical characteristics of the foundation and the fill materials, an interpretation of the unusual behaviour has been attempted

Antidepressant-like Effect of Extracts From Urtica Dioica in Mice Model of Depression

Urtica dioica (Stinging nettle) leaves have been used as a traditional medicine to treatrheumatoid arthritis, to alleviate rheumatic pain benign prostatic hyperplasia (BPH), diuretic and prevention of kidney stones by local people in Middle East region especially in Iran, Turkey and East Europe. Hence, this investigation evaluates the antidepressant effect of selected crude extracts in the forced swimming test (FST) and tail suspension test (TST), two models predictive of antidepressant activity. The acute treatment of mice with extracts by intra-peritoneal (i.p.) route significantly reduced the immobility time in the FST (50 and 100 mg/kg) and TST (50 and 100 mg/kg), as compared to positive controls (haloperidol and fluoxetine) at 1 and 10 mg/kg, respectively. On the third day of experiment, a significant decrease of mobility was observed for chloroform extract (CE I) and butanol extract (BE II) compared to first day. CE I and BE II led to reduction of immobility time, as the selected extracts with two doses administered were different compared to the control, in the FST method by 65.37% and53.92% for 100 mg/kg, respectively. However, CE I showed the best result compared to our positive controls. Similar results of increased antidepressant effect, that was, of immobility time depending on the concentration administered, were obtained with the TST method. Also our data showed that there was no significant differences between doses (50 and 100 mg/kg). The results suggested that the antidepressant action of the butanol extract and of U. dioica its fraction (BE II2) was mediated by an interaction with 5-hydroxytrptamine (5-HT). U. dioica showed a potential source for the isolation of important natural products with antidepressant-like properties. However, further studies are still require

Coined quantum walks on percolation graphs

Quantum walks, both discrete (coined) and continuous time, form the basis of several quantum algorithms and have been used to model processes such as transport in spin chains and quantum chemistry. The enhanced spreading and mixing properties of quantum walks compared with their classical counterparts have been well-studied on regular structures and also shown to be sensitive to defects and imperfections in the lattice. As a simple example of a disordered system, we consider percolation lattices, in which edges or sites are randomly missing, interrupting the progress of the quantum walk. We use numerical simulation to study the properties of coined quantum walks on these percolation lattices in one and two dimensions. In one dimension (the line) we introduce a simple notion of quantum tunneling and determine how this affects the properties of the quantum walk as it spreads. On two-dimensional percolation lattices, we show how the spreading rate varies from linear in the number of steps down to zero, as the percolation probability decreases to the critical point. This provides an example of fractional scaling in quantum walk dynamics.Comment: 25 pages, 14 figures; v2 expanded and improved presentation after referee comments, added extra figur

Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney

Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag[superscript −/−] mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag[superscript −/−] mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag[superscript −/−] liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.National Institutes of Health (U.S.) (Grant R01-CA055042)National Institutes of Health (U.S.) (Grant R01-CA149261)National Institutes of Health (U.S.) (Grant P30-ES02109)Ellison Medical Foundatio

Prophet Inequalities for IID Random Variables from an Unknown Distribution

A central object in optimal stopping theory is the single-choice prophet inequality for independent, identically distributed random variables: given a sequence of random variables X1, . . . , Xn drawn independently from a distribution F , the goal is to choose a stopping time τ so as to maximize α such that for all distributions F we have E[Xτ ] ≥ α · E[maxt Xt ]. What makes this problem challenging is that the decision whether τ = t may only depend on the values of the random variables X1, . . . , Xt and on the distribution F . For a long time the best known bound for the problem had been α ≥ 1 − 1/e ≈ 0.632, but quite recently a tight bound of α ≈ 0.745 was obtained. The case where F is unknown, such that the decision whether τ = t may depend only on the values of the random variables X1, . . . , Xt , is equally well motivated but has received much less attention. A straightforward guarantee for this case of α ≥ 1/e ≈ 0.368 can be derived from the solution to the secretary problem, where an arbitrary set of values arrive in random order and the goal is to maximize the probability of selecting the largest value. We show that this bound is in fact tight. We then investigate the case where the stopping time may additionally depend on a limited number of samples from F , and show that even with o(n) samples α ≤ 1/e. On the other hand, n samples allow for a significant improvement, while O(n2) samples are equivalent to knowledge of the distribution: specifically, with n samples α ≥ 1 − 1/e ≈ 0.632 and α ≤ ln(2) ≈ 0.693, and with O(n2) samples α ≥ 0.745 − ε for any ε > 0

Expanding clinical phenotype and novel insights into the pathogenesis of ICOS deficiency

Background: Inducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novel ICOS mutations resulting in a common variable immunodeficiency (CVID)–like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte–associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition. Methods: A combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA. Results: Four novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+ T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy. Conclusions: ICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation

Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials

Background: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). Objective: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. Methods: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti–thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. Results: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of −2.07 (95% confidence interval: −6.04 to 1.90) for positive antibodies versus 0.89 (−1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores—adjusted between-group difference 1.75 (−3.60 to 7.09) for positive antibodies versus 1.14 (−1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. Conclusions: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4

Does it look safe? An eye tracking study into the visual aspects of fear of crime

Studies of fear of crime often focus on demographic and social factors, but these can be difficult to change. Studies of visual aspects have suggested that features reflecting incivilities, such as litter, graffiti, and vandalism increase fear of crime, but methods often rely on participants actively mentioning such aspects, and more subtle, less conscious aspects may be overlooked. To address these concerns, the present study examined people’s eye movements while they judged scenes for safety. Forty current and former university students were asked to rate images of day-time and night-time scenes of Lincoln, UK (where they studied) and Egham, UK (unfamiliar location) for safety, maintenance and familiarity, while their eye movements were recorded. Another twenty-five observers not from Lincoln or Egham rated the same images in an internet survey. Ratings showed a strong association between safety and maintenance and lower safety ratings for night-time scenes for both groups, in agreement with earlier findings. Eye movements of the Lincoln participants showed increased dwell times on buildings, houses, and vehicles during safety judgments, and increased dwell times on streets, pavements, and markers of incivilities for maintenance. Results confirm that maintenance plays an important role in perceptions of safety, but eye movements suggest that observers also look for indicators of current or recent presence of people

Evaluation of a robotic technique for transrectal MRI-guided prostate biopsies

Item does not contain fulltextOBJECTIVES: To evaluate the accuracy and speed of a novel robotic technique as an aid to perform magnetic resonance image (MRI)-guided prostate biopsies on patients with cancer suspicious regions. METHODS: A pneumatic controlled MR-compatible manipulator with 5 degrees of freedom was developed in-house to guide biopsies under real-time imaging. From 13 consecutive biopsy procedures, the targeting error, biopsy error and target displacement were calculated to evaluate the accuracy. The time was recorded to evaluate manipulation and procedure time. RESULTS: The robotic and manual techniques demonstrated comparable results regarding mean targeting error (5.7 vs 5.8 mm, respectively) and mean target displacement (6.6 vs 6.0 mm, respectively). The mean biopsy error was larger (6.5 vs 4.4 mm) when using the robotic technique, although not significant. Mean procedure and manipulation time were 76 min and 6 min, respectively using the robotic technique and 61 and 8 min with the manual technique. CONCLUSIONS: Although comparable results regarding accuracy and speed were found, the extended technical effort of the robotic technique make the manual technique - currently - more suitable to perform MRI-guided biopsies. Furthermore, this study provided a better insight in displacement of the target during in vivo biopsy procedures.01 februari 201