Exploring tradeoffs in pleiotropy and redundancy using evolutionary computing

Evolutionary computation algorithms are increasingly being used to solve optimization problems as they have many advantages over traditional optimization algorithms. In this paper we use evolutionary computation to study the trade-off between pleiotropy and redundancy in a client-server based network. Pleiotropy is a term used to describe components that perform multiple tasks, while redundancy refers to multiple components performing one same task. Pleiotropy reduces cost but lacks robustness, while redundancy increases network reliability but is more costly, as together, pleiotropy and redundancy build flexibility and robustness into systems. Therefore it is desirable to have a network that contains a balance between pleiotropy and redundancy. We explore how factors such as link failure probability, repair rates, and the size of the network influence the design choices that we explore using genetic algorithms.Comment: 10 pages, 6 figure

Validation of a French language version of the Early Childhood Oral Health Impact Scale (ECOHIS)

© 2008 Li et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Optimal dimensional synthesis of a symmetrical five-bar planar upper-extremity neuromotor device

Individuals with hemiplegia suffer from impaired arm movements that appear as a marked change in arm stiffness. A quantitative measure of arm stiffness would characterize rehabilitation therapy effectively, while little mechanism is designed to implement the function. A symmetrical five-bar linkage consisting of two revolute joints and three prismatic joints is presented. Inverse kinematics and forward kinematics are obtained first. Then inverse singularities and direct singularities of the mechanism are gained. Based on the results of kinematics analysis, the global stiffness index is defined. Finally, optimal dimensional synthesis of the mechanism in terms of maximum stiffness is conducted by genetic algorithms. The calculation results shows that when length of both the two linkage a=830 mm, interacting angle of the two guides 2d=4.48 radian, and maximum range of displacement of the two carriers dmax=940 mm, the mechanism achieves highest rigidity and its workspace is singularity-free, which covers the human left and right arm range of motion. The proposed novel mechanism featuring high rigidity and a singularity-free workspace can provides rehabilitation training, but also solves the problem of quantitative measure of arm stiffness

Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women.

IntroductionYoung women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women.MethodsData for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010.ResultsWith up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease.ConclusionsAmong AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women

Large capacitance enhancement and negative compressibility of two-dimensional electronic systems at LaAlO3_3/SrTiO3_3 interfaces

Novel electronic systems forming at oxide interfaces comprise a class of new materials with a wide array of potential applications. A high mobility electron system forms at the LaAlO$_3$/SrTiO$_3$ interface and, strikingly, both superconducts and displays indications of hysteretic magnetoresistance. An essential step for device applications is establishing the ability to vary the electronic conductivity of the electron system by means of a gate. We have fabricated metallic top gates above a conductive interface to vary the electron density at the interface. By monitoring capacitance and electric field penetration, we are able to tune the charge carrier density and establish that we can completely deplete the metallic interface with small voltages. Moreover, at low carrier densities, the capacitance is significantly enhanced beyond the geometric capacitance for the structure. In the same low density region, the metallic interface overscreens an external electric field. We attribute these observations to a negative compressibility of the electronic system at the interface. Similar phenomena have been observed previously in semiconducting two-dimensional electronic systems. The observed compressibility result is consistent with the interface containing a system of mobile electrons in two dimensions.Comment: 4 figures in main text; 4 figures in the supplemen

The Relationship Between Patient Safety Outcomes and Hospital Characteristics

To augment the discussion of the extent to which quality is universal, this study presents the results of an analysis of 13.5 million inpatient discharges from 1,640 general hospitals from 16 states. Factor analysis was performed on 588 general U.S. hospitals and 18 PSIs were reduced to seven factors. Hospital tiers were profiled utilizing demographic variables. Contrary to expectations the best quality hospitals tended to be smaller, non-teaching hospitals whereas larger, teaching hospitals tended to be poor quality performers. This analysis provided evidence patient safety quality rates may not be universal and organizational context may be an important influencing factor

Engineered Fn3 Protein has Targeted Therapeutic Effect on Mesothelin-Expressing Cancer Cells and Increases Tumor Cell Sensitivity to Chemotherapy

Mesothelin is a protein expressed at high levels on the cell surface in a variety of cancers, with limited expression in healthy tissues. The presence of mesothelin on tumor tissue correlates with increased invasion and metastasis, and resistance to traditional chemotherapies, through mechanisms that remain poorly understood. Molecules that specifically recognize mesothelin and interrupt its contribution to tumor progression have significant potential for targeted therapy and targeted drug delivery applications. A number of mesothelin-targeting therapies are in preclinical and clinical development, although none are currently approved for routine clinical use. In this work, we report the development of a mesothelin-targeting protein based on the fibronectin type-III non-antibody protein scaffold, which offers opportunities for applications where antibodies have limitations. We engineered protein variants that bind mesothelin with high affinity and selectively initiate apoptosis in tumor cells expressing mesothelin. Interestingly, apoptosis does not occur through a caspase-mediated pathway and does not require downregulation of cell-surface mesothelin, suggesting a currently unknown pathway through which mesothelin contributes to cancer progression. Importantly, simultaneous treatment with mesothelin-binding protein and chemotherapeutic mitomycin C had a greater cytotoxic effect on mesothelin-positive cells compared to either molecule alone, underscoring the potential for combination therapy including biologics targeting mesothelin

A Review of Family-Based Tests for Linkage Disequilibrium between a Quantitative Trait and a Genetic Marker

Quantitative trait transmission/disequilibrium tests (quantitative TDTs) are commonly used in family-based genetic association studies of quantitative traits. Despite the availability of various quantitative TDTs, some users are not aware of the properties of these tests and the relationships between them. This review aims at outlining the broad features of the various quantitative TDT procedures carried out in the frequently used QTDT and FBAT packages. Specifically, we discuss the “Rabinowitz” and the “Monks-Kaplan” procedures, as well as the various “Abecasis” and “Allison” regression-based procedures. We focus on the models assumed in these tests and the relationships between them. Moreover, we discuss what hypotheses are tested by the various quantitative TDTs, what testing procedures are best suited to various forms of data, and whether the regression-based tests overcome population stratification problems. Finally, we comment on power considerations in the choice of the test to be used. We hope this brief review will shed light on the similarities and differences of the various quantitative TDTs

Towards an Intelligent Database System Founded on the SP Theory of Computing and Cognition

The SP theory of computing and cognition, described in previous publications, is an attractive model for intelligent databases because it provides a simple but versatile format for different kinds of knowledge, it has capabilities in artificial intelligence, and it can also function like established database models when that is required. This paper describes how the SP model can emulate other models used in database applications and compares the SP model with those other models. The artificial intelligence capabilities of the SP model are reviewed and its relationship with other artificial intelligence systems is described. Also considered are ways in which current prototypes may be translated into an 'industrial strength' working system