Fail-safe optimization of viscous dampers for seismic retrofitting

This paper presents a new optimization approach for designing minimum-cost fail-safe distributions of fluid viscous dampers for seismic retrofitting. Failure is modeled as either complete damage of the dampers or partial degradation of the dampers' properties. In general, this leads to optimization problems with large number of constraints. Thus, the use of a working-set optimization algorithm is proposed. The main idea is to solve a sequence of relaxed optimization sub-problems with a small sub-set of all constraints. The algorithm terminates once a solution of a sub-problem is found that satisfies all the constraints of the problem. The retrofitting cost is minimized with constraints on the inter-story drifts at the peripheries of frame structures. The structures considered are subjected to a realistic ensemble of ground motions, and their response is evaluated with time-history analyses. The transient optimization problem is efficiently solved with a gradient-based sequential linear programming algorithm. The gradients of the response functions are calculated with a consistent adjoint sensitivity analysis procedure. Promising results attained for 3-D irregular frames are presented and discussed. The numerical results highlight the fact that the optimized layout and size of the dampers can change significantly even for moderate levels of damage

Analysis of gene expression profiles in HeLa cells in response to overexpression or siRNA-mediated depletion of NASP

<p>Abstract</p> <p>Background</p> <p>NASP (Nuclear Autoantigenic Sperm Protein) is a linker histone chaperone required for normal cell division. Changes in NASP expression significantly affect cell growth and development; loss of gene function results in embryonic lethality. However, the mechanism by which NASP exerts its effects in the cell cycle is not understood. To understand the pathways and networks that may involve NASP function, we evaluated gene expression in HeLa cells in which NASP was either overexpressed or depleted by siRNA.</p> <p>Methods</p> <p>Total RNA from HeLa cells overexpressing NASP or depleted of NASP by siRNA treatment was converted to cRNA with incorporation of Cy5-CTP (experimental samples), or Cy3-CTP (control samples). The labeled cRNA samples were hybridized to whole human genome microarrays (Agilent Technologies, Wilmington, Delaware, USA). Various gene expression analysis techniques were employed: Significance Analysis of Microarrays (SAM), Expression Analysis Systematic Explorer (EASE), and Ingenuity Pathways Analysis (IPA).</p> <p>Results</p> <p>From approximately 36 thousand genes present in a total human genome microarray, we identified a set of 47 up-regulated and 7 down-regulated genes as a result of NASP overexpression. Similarly we identified a set of 56 up-regulated and 71 down-regulated genes as a result of NASP siRNA treatment. Gene ontology, molecular network and canonical pathway analysis of NASP overexpression demonstrated that the most significant changes were in proteins participating in organismal injury, immune response, and cellular growth and cancer pathways (major "hubs": TNF, FOS, EGR1, NFκB, IRF7, STAT1, IL6). Depletion of NASP elicited the changed expression of proteins involved in DNA replication, repair and development, followed by reproductive system disease, and cancer and cell cycle pathways (major "hubs": E2F8, TP53, FGF, FSH, FST, hCG, NFκB, TRAF6).</p> <p>Conclusion</p> <p>This study has demonstrated that NASP belongs to a network of genes and gene functions that are critical for cell survival. We have confirmed the previously reported interactions between NASP and HSP90, HSP70, histone H1, histone H3, and TRAF6. Overexpression and depletion of NASP identified overlapping networks that included TNF as a core protein, confirming that both high and low levels of NASP are detrimental to cell cycle progression. Networks with cancer-related functions had the highest significance, however reproductive networks containing follistatin and FSH were also significantly affected, which confirmed NASP's important role in reproductive tissues. This study revealed that, despite some overlap, each response was associated with a unique gene signature and placed NASP in important cell regulatory networks.</p

Temporal Patterns of Medications Dispensed to Children and Adolescents in a National Insured Population

This study aimed to comprehensively describe prevalence and temporal dispensing patterns for medications prescribed to children and adolescents in the United States. Participants were 1.6 million children (49% female) under 18 years old enrolled in a nation-wide, employer-provided insurance plan. All medication claims from 1999–2006 were reviewed retrospectively. Drugs were assigned to 16 broad therapeutic categories. Effects of trend over time, seasonality, age and gender on overall and within category prevalence were examined. Results: Mean monthly prevalence for dispensed medications was 23.5% (range 19.4–27.5), with highest rates in winter and lowest in July. The age group with the highest prevalence was one-year-old children. On average each month, 17.1% of all children were dispensed a single drug and 6.4% were dispensed two or more. Over time, prevalence for two or more drugs did not change, but the proportion of children dispensed a single drug decreased (slope -.02%, p = .001). Overall, boys had higher monthly rates than girls (average difference 0.9%, p = .002). However, differences by gender were greatest during middle childhood, especially for respiratory and central nervous system agents. Contraceptives accounted for a large proportion of dispensed medication to older teenage girls. Rates for the drugs with the highest prevalence in this study were moderately correlated (average Pearson r.66) with those from a previously published national survey. Conclusion: On average, nearly one quarter of a population of insured children in the United States was dispensed medication each month. This rate decreased somewhat over time, primarily because proportionally fewer children were dispensed a single medication. The rate for two or more drugs dispensed simultaneously remained steady

Case-control study on uveal melanoma (RIFA): rational and design

BACKGROUND: Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation. METHODS/DESIGN: We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding

Characterization of Leishmania donovani MCM4: Expression Patterns and Interaction with PCNA

Events leading to origin firing and fork elongation in eukaryotes involve several proteins which are mostly conserved across the various eukaryotic species. Nuclear DNA replication in trypanosomatids has thus far remained a largely uninvestigated area. While several eukaryotic replication protein orthologs have been annotated, many are missing, suggesting that novel replication mechanisms may apply in this group of organisms. Here, we characterize the expression of Leishmania donovani MCM4, and find that while it broadly resembles other eukaryotes, noteworthy differences exist. MCM4 is constitutively nuclear, signifying that, unlike what is seen in S.cerevisiae, varying subcellular localization of MCM4 is not a mode of replication regulation in Leishmania. Overexpression of MCM4 in Leishmania promastigotes causes progress through S phase faster than usual, implicating a role for MCM4 in the modulation of cell cycle progression. We find for the first time in eukaryotes, an interaction between any of the proteins of the MCM2-7 (MCM4) and PCNA. MCM4 colocalizes with PCNA in S phase cells, in keeping with the MCM2-7 complex being involved not only in replication initiation, but fork elongation as well. Analysis of a LdMCM4 mutant indicates that MCM4 interacts with PCNA via the PIP box motif of MCM4 - perhaps as an integral component of the MCM2-7 complex, although we have no direct evidence that MCM4 harboring a PIP box mutation can still functionally associate with the other members of the MCM2-7 complex- and the PIP box motif is important for cell survival and viability. In Leishmania, MCM4 may possibly help in recruiting PCNA to chromatin, a role assigned to MCM10 in other eukaryotes

Remarks on the Cauchy functional equation and variations of it

This paper examines various aspects related to the Cauchy functional equation $f(x+y)=f(x)+f(y)$, a fundamental equation in the theory of functional equations. In particular, it considers its solvability and its stability relative to subsets of multi-dimensional Euclidean spaces and tori. Several new types of regularity conditions are introduced, such as a one in which a complex exponent of the unknown function is locally measurable. An initial value approach to analyzing this equation is considered too and it yields a few by-products, such as the existence of a non-constant real function having an uncountable set of periods which are linearly independent over the rationals. The analysis is extended to related equations such as the Jensen equation, the multiplicative Cauchy equation, and the Pexider equation. The paper also includes a rather comprehensive survey of the history of the Cauchy equation.Comment: To appear in Aequationes Mathematicae (important remark: the acknowledgments section in the official paper exists, but it appears before the appendix and not before the references as in the arXiv version); correction of a minor inaccuracy in Lemma 3.2 and the initial value proof of Theorem 2.1; a few small improvements in various sections; added thank

Global, regional, and national burden of stroke, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Stroke is a leading cause of mortality and disability worldwide and the economic costs of treatment and post-stroke care are substantial. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic, comparable method of quantifying health loss by disease, age, sex, year, and location to provide information to health systems and policy makers on more than 300 causes of disease and injury, including stroke. The results presented here are the estimates of burden due to overall stroke and ischaemic and haemorrhagic stroke from GBD 2016. Methods: We report estimates and corresponding uncertainty intervals (UIs), from 1990 to 2016, for incidence, prevalence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs). DALYs were generated by summing YLLs and YLDs. Cause-specific mortality was estimated using an ensemble modelling process with vital registration and verbal autopsy data as inputs. Non-fatal estimates were generated using Bayesian meta-regression incorporating data from registries, scientific literature, administrative records, and surveys. The Socio-demographic Index (SDI), a summary indicator generated using educational attainment, lagged distributed income, and total fertility rate, was used to group countries into quintiles. Findings: In 2016, there were 5·5 million (95% UI 5·3 to 5·7) deaths and 116·4 million (111·4 to 121·4) DALYs due to stroke. The global age-standardised mortality rate decreased by 36·2% (−39·3 to −33·6) from 1990 to 2016, with decreases in all SDI quintiles. Over the same period, the global age-standardised DALY rate declined by 34·2% (−37·2 to −31·5), also with decreases in all SDI quintiles. There were 13·7 million (12·7 to 14·7) new stroke cases in 2016. Global age-standardised incidence declined by 8·1% (−10·7 to −5·5) from 1990 to 2016 and decreased in all SDI quintiles except the middle SDI group. There were 80·1 million (74·1 to 86·3) prevalent cases of stroke globally in 2016; 41·1 million (38·0 to 44·3) in women and 39·0 million (36·1 to 42·1) in men. Interpretation: Although age-standardised mortality rates have decreased sharply from 1990 to 2016, the decrease in age-standardised incidence has been less steep, indicating that the burden of stroke is likely to remain high. Planned updates to future GBD iterations include generating separate estimates for subarachnoid haemorrhage and intracerebral haemorrhage, generating estimates of transient ischaemic attack, and including atrial fibrillation as a risk factor. Funding: Bill & Melinda Gates Foundatio