Many real-world optimisation problems approached by evolutionary algorithms are subject to noise. When noise is present, the evolutionary selection process may become unstable and the convergence of ...the optimisation adversely affected. In this paper, we present a new technique that efficiently deals with noise in multi-objective optimisation. This technique aims at preventing the propagation of inferior solutions in the evolutionary selection due to noisy objective values. This is done by using an iterative resampling procedure that reduces the noise until the likelihood of selecting the correct solution reaches a given confidence level. To achieve an efficient utilisation of resources, the number of samples used per solution varies based on the amount of noise in the present area of the search space. The proposed algorithm is evaluated on the ZDT benchmark problems and two complex real-world problems of manufacturing optimisation. The first real-world problem concerns the optimisation of engine component manufacturing in aviation industry, while the second real-world problem concerns the optimisation of a camshaft machining line in automotive industry. The results from the optimisations indicate that the proposed technique is successful in reducing noise, and it competes successfully with other noise handling techniques.
Many real-world manufacturing problems are too complex to be modelled analytically. For these problems, simulation can be a powerful tool for system analysis and optimisation. While traditional ...optimisation methods have been unable to cope with the complexities of many problems approached by simulation, evolutionary algorithms have proven to be highly useful. This paper describes how simulation and evolutionary algorithms have been combined to improve a manufacturing cell at Volvo Aero in Sweden. This cell produces high-technology engine components for civilian and military airplanes, and also for space rockets. Results from the study show that by using simulation and evolutionary algorithms, it is possible to increase the overall utilisation of the cell and at the same time decrease the number of overdue components.
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Background
Periconceptional consumption of folic acid can reduce a woman's risk of having a neural tube defect (NTD)‐affected pregnancy, particularly in high‐prevalence areas such as ...northern China; however, information about the effect of folic acid on sex‐specific or phenotype‐specific spina bifida prevalence is lacking.
Methods
We used data from the China‐U.S. NTD Prevention Project during which women were asked to take a daily pill containing 400 μg of folic acid without other vitamins to reduce their risk of having an NTD‐affected pregnancy. We used data from birth defect surveillance and births from 1993 through 1996 from a high‐prevalence region located in five counties in northern China to evaluate these effects. We also examined the distribution of spina bifida phenotypes‐‐categorizing lesions in the cervicothoracic region as high lesions and those in the lumbosacral region as low lesions.
Results
Among 21,536 women who took folic acid at any time before and during early pregnancy and 56,541 women who did not take folic acid, we identified 18 and 115 women, respectively, with spina bifida‐affected pregnancies of ≥ 20 weeks’ gestation. Among the women who did and did not take any folic acid, the prevalences of spina bifida were 8.4 per 10,000 pregnancies and 20.3 per 10,000, respectively (risk reduction ~59%). Among women who did and did not take any folic acid as part of the prevention project, the spina bifida prevalences among female offspring were 8.8 and 24.2 per 10,000 pregnancies, respectively (risk reduction ~64%), and the prevalences among male offspring were 8.0 and 17.0 per 10,000, respectively (risk reduction ~53%). Among women who did and did not take any folic acid, the prevalences of high spina bifida lesions among offspring were 3.3 and 11.0 per 10,000 pregnancies, respectively (risk reduction ~70%), and prevalences of low spina bifida lesions among offspring were 4.6 and 8.5 per 10,000 pregnancies, respectively (risk reduction ~45%). This difference was statistically significant at p<0.01 and among women with female offspring, the risk reduction was even greater for high lesions vs. low lesions.
Discussion and Conclusions
These findings suggest that the folic acid effect on neural tube closure is not limited to any one spina bifida phenotype; however, it appears that the effect may differ by level of lesion and offspring sex. Among women who consumed 400 μg of folic acid daily, compared with those with male offspring those with female offspring experienced a greater reduction in risk of spina bifida this reduction in risk among female offspring was greater for high lesions than for low lesions. The findings are also consistent with observations in seven Canadian provinces where the proportion of cervicothoracic lesions decreased in all regions after fortification. Examination of these variations in folic acid effects may be helpful in identifying factors important in the pathogenesis of spina bifida and other neural tube defects.
Support or Funding Information
CDC internal funding only
Malignant pleural mesothelioma is a particularly aggressive and locally invasive malignancy with a poor prognosis despite advances in understanding of cancer cell biology and development of new ...therapies. At the cellular level, cultured mesothelioma cells present a mesenchymal appearance and a strong capacity for local cellular invasion. One important but underexplored area of mesothelioma cell biology is intercellular communication. Our group has previously characterized in multiple histological subtypes of mesothelioma a unique cellular protrusion known as tunneling nanotubes (TnTs). TnTs are long, actin filament-based, narrow cytoplasmic extensions that are non-adherent when cultured in vitro and are capable of shuttling cellular cargo between connected cells. Our prior work confirmed the presence of nanotube structures in tumors resected from patients with human mesothelioma. In our current study, we quantified the number of TnTs/cell among various mesothelioma subtypes and normal mesothelial cells using confocal microscopic techniques. We also examined changes in TnT length over time in comparison to cell proliferation. We further examined potential approaches to the in vivo study of TnTs in animal models of cancer. We have developed novel approaches to study TnTs in aggressive solid tumor malignancies and define fundamental characteristics of TnTs in malignant mesothelioma. There is mounting evidence that TnTs play an important role in intercellular communication in mesothelioma and thus merit further investigation of their role in vivo.
Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice ...disrupts gut homeostasis, characterized by increased proportions of colonic CX3CR1hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3CR1hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis.
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•Imiquimod-induced psoriasis (IMQ-pso) induces gut microbiota dysbiosis•Gut microbiota in IMQ-pso secretes high levels of succinate•High succinate in IMQ-pso induces proliferation of colonic CX3CR1hi macrophages•Impaired gut homeostasis in IMQ-pso aggravates DSS-induced colitis in mice
Patients with psoriasis often develop inflammatory bowel disease. Pinget et al. show that psoriasis disrupts the gut microbiota, increasing microbial production of succinate and pro-inflammatory ligands, inducing the proliferation and activation of colonic CX3CR1hi macrophages. The authors propose a model linking psoriasis and inflammatory bowel disease.
BioBin is a bioinformatics software package developed to automate the process of binning rare variants into groups for statistical association analysis using a biological knowledge-driven framework. ...BioBin collapses variants into biological features such as genes, pathways, evolutionary conserved regions (ECRs), protein families, regulatory regions, and others based on user-designated parameters. BioBin provides the infrastructure to create complex and interesting hypotheses in an automated fashion thereby circumventing the necessity for advanced and time consuming scripting.
In this manuscript, we describe the software package for BioBin, along with type I error and power simulations to demonstrate the strengths and various customizable features and analysis options of this variant binning tool.
Simulation testing highlights the utility of BioBin as a fast, comprehensive and expandable tool for the biologically-inspired binning and analysis of low-frequency variants in sequence data.
The BioBin software package has the capability to transform and streamline the analysis pipelines for researchers analyzing rare variants. This automated bioinformatics tool minimizes the manual effort of creating genomic regions for binning such that time can be spent on the much more interesting task of statistical analyses. This software package is open source and freely available from http://ritchielab.com/software/biobin-download.
Developmental reprogramming techniques have been used to generate induced pluripotent stem (iPS) cells from both normal and malignant cells. The derivation of iPS cells from cancer has the potential ...to provide a unique scientific tool to overcome challenges associated with the establishment of cell lines from primary patient samples and a readily expandable source of cells that may be used to model the initial disease. In the current study we developmentally reprogrammed a metastatic Ewing sarcoma (EWS) cell line to a meta-stable embryonic stem (ES)-like state sharing molecular and phenotypic features with previously established ES and iPS cell lines. EWS-iPS cells exhibited a pronounced drug resistant phenotype despite persistent expression of the oncogenic EWS-FLI1 fusion transcript. This included resistance to compounds that specifically target downstream effector pathways of EWS-FLI1, such as MAPK/ERK and PI3K/AKT, which play an important role in EWS pathogenesis. EWS-iPS cells displayed tumor initiation abilities in vivo and formed tumors exhibiting characteristic Ewing histopathology. In parallel, EWS-iPS cells re-differentiated in vitro recovered sensitivity to molecularly targeted chemotherapeutic agents, which reiterated pathophysiological features of the cells from which they were derived. These data suggest that EWS-iPS cells may provide an expandable disease model that could be used to investigate processes modulating oncogenesis, metastasis, and chemotherapeutic resistance in EWS.
Many power-system-related effects and sources of man-made noise cause impulsive interference. Due to its wideband nature, this type of interference is difficult to remove by filtering. This paper ...presents a system that is capable of locating and characterizing sources of impulsive interference. It is based on three separate asynchronous receiving units. The operating principle of the location system is outlined, and a prototype practical implementation is described. The location accuracies achieved both in the laboratory and in practical field trials are reported.
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4006
Background: Some studies in patients with resected pancreatic cancer have suggested that expression of the human equilibrative nucleoside transporter (hENT1) may be predictive of ...improved survival from gemcitabine but these have either been based on retrospective non-randomized studies or in one study the principal treatment was chemoradiation. The samples collected from the adjuvant ESPAC1/3 randomized trials have provided a unique opportunity to assess to REMARK standards the therapeutic predictability of hENT1 in patients undergoing resection for pancreatic cancer. Methods: Tissue Microarrays (TMAs) were prepared using paraffin embedded tumor specimens from patients randomized to gemcitabine or 5FU/Folinic acid in the ESPAC-1 and -3 trials. Cores were given an H-Score depending on the level of staining with the 10D7G2 anti-hENT1 antibody. Groups were compared using Kaplan-Meier and Cox proportional hazards. Results: Scores were obtained for 176 gemcitabine treated and 176 5FU treated patients. The overall median H-Score was 48 and patients were classified as having high hENT1 if the mean score for their cores was above this. Median overall survival for gemcitabine treated patients was 23.4 (95% CI: 18.3, 26.0) months versus 23.5 (95% CI: 19.8, 27.3) months for 5FU treated patients (χ
2
1
= 0.24, P = 0.623). In the gemcitabine group A significantly lower survival (χ
2
1
= 9.87, P = 0.002) was noted with low hENT1 (median survival 17.1 (95% CI: 14.3, 23.8) versus 26.2 (95% CI: 21.2, 31.4) months). Median survival was 25.6 (95% CI: 20.1, 27.9) and 21.9 (95% CI: 16.0, 28.3) months respectively for high and low hENT1 in the 5FU group, a non-significant difference (χ
2
1
= 0.83, P = 0.362). Multivariate analysis confirmed hENT1 expression as a predictive marker in gemcitabine (Wald χ
2
= 7.10, P = 0.008) but not 5-fluorouracil (Wald χ
2
=0.34, P = 0.560) groups. Conclusions: The study supports use of gemcitabine in patients with high tumor hENT1 expression and 5-fluorouracil in patients with low hENT1.
The latest in a series exploring twenty-first-century governance, this new volume examines the use of market means to pursue public goals. ¡°Market-based governance¡± includes both the delegation of ...traditionally governmental functions to private players, and the importation into government of market-style management approaches and mechanisms of accountability. The contributors (all from Harvard University) assess market-based governance from four perspectives: The ¡°demand side¡± deals with new, revised, or newly important forms of interaction between government and the market where the public sector is the ¡°customer.¡± Chapters in this section include Steve Kelman on federal procurement reform, Karen Eggleston and Richard Zeckhauser on contracting for health care, and Peter Frumkin. The ¡°supply side¡± section deals with unsettled questions about government¡¯s role as a provider (rather than a purchaser) within the market system. Contributors include Georges de Menil, Frederick Schauer and Virginia Wise. A third section explores experiments with market-based arrangements for orchestrating accountabilityoutsidegovernment by altering the incentives that operate inside market institutions. Chapters include Robert Stavins on market-based environmental policy, Archon Fung on ¡°social markets,¡± and Cary Coglianese and David Lazer. The final section examines both the upside and the downside of the market-based approach to improving governance. Contributors include Elaine Kamarck, John D. Donahue, Mark Moore, and Robert Behn. An introduction by John D. Donahue frames market-based governance as an effort to engineer into public work some of the ¡°intensive¡± accountability that characterizes markets without surrendering the ¡°extensive¡± accountability of conventional government. A preface by Joseph S. Nye Jr. sets the book in the context of a larger inquiry into the future of governance.
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