Variable interaction in multi-objective optimization problems

14th International Conference on Parallel Problem Solving from Nature – PPSN XIV, 2016-09-17, 2016-09-21, Edinburgh, UK, pp. 399 - 409This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The final publication is available at link.springer.comVariable interaction is an important aspect of a problem, which reflects its structure, and has implications on the design of efficient optimization algorithms. Although variable interaction has been widely studied in the global optimization community, it has rarely been explored in the multi-objective optimization literature. In this paper, we empirically and analytically study the variable interaction structures of some popular multi-objective benchmark problems. Our study uncovers nontrivial variable interaction structures for the ZDT and DTLZ benchmark problems which were thought to be either separable or non-separable

A 95 GHz Class I Methanol Maser Survey Toward A Sample of GLIMPSE Point Sources Associated with BGPS Clumps

We report a survey with the Purple Mountain Observatory (PMO) 13.7-m radio telescope for class I methanol masers from the 95 GHz (8_0 - 7_1 A^+) transition. The 214 target sources were selected by combining information from both the Spitzer GLIMPSE and 1.1 mm BGPS survey catalogs. The observed sources satisfy both the GLIMPSE mid-IR criteria of [3.6]-[4.5]>1.3, [3.6]-[5.8]>2.5, [3.6]-[8.0]>2.5 and 8.0 um magnitude less than 10, and also have an associated 1.1 mm BGPS source. Class I methanol maser emission was detected in 63 sources, corresponding to a detection rate of 29% for this survey. For the majority of detections (43), this is the first identification of a class I methanol maser associated with these sources. We show that the intensity of the class I methanol maser emission is not closely related to mid-IR intensity or the colors of the GLIMPSE point sources, however, it is closely correlated with properties (mass and beam-averaged column density) of the BGPS sources. Comparison of measures of star formation activity for the BGPS sources with and without class I methanol masers indicate that the sources with class I methanol masers usually have higher column density and larger flux density than those without them. Our results predict that the criteria log(S_{int})22.1, which utilizes both the integrated flux density (S_{int}) and beam-averaged column density (N_{H_{2}}^{beam}) of the BGPS sources, are very efficient for selecting sources likely to have an associated class I methanol maser. Our expectation is that searches using these criteria will detect 90% of the predicted number of class I methanol masers from the full BGPS catalog (~ 1000), and do so with a high detection efficiency (~75%).Comment: Accepted for publication in ApJ Supplement. 58 pages, 12 figures, 7 table

RPGR protein complex regulates proteasome activity and mediates store-operated calcium entry

Ciliopathies are a group of genetically heterogeneous disorders, characterized by defects in cilia genesis or maintenance. Mutations in the RPGR gene and its interacting partners, RPGRIP1 and RPGRIP1L, cause ciliopathies, but the function of their proteins remains unclear. Here we show that knockdown (KD) of RPGR, RPGRIP1 or RPGRIP1L in hTERT-RPE1 cells results in abnormal actin cytoskeleton organization. The actin cytoskeleton rearrangement is regulated by the small GTPase RhoA via the planar cell polarity (PCP) pathway. RhoA activity was upregulated in the absence of RPGR, RPGRIP1 or RPGRIP1L proteins. In RPGR, RPGRIP1 or RPGRIP1L KD cells, we observed increased levels of DVl2 and DVl3 proteins, the core components of the PCP pathway, due to impaired proteasomal activity. RPGR, RPGRIP1 or RPGRIP1L KD cells treated with thapsigargin (TG), an inhibitor of sarcoendoplasmic reticulum Ca2+ - ATPases, showed impaired store-operated Ca2+ entry (SOCE), which is mediated by STIM1 and Orai1 proteins. STIM1 was not localized to the ER-PM junction upon ER store depletion in RPGR, RPGRIP1 or RPGRIP1L KD cells. Our results demonstrate that the RPGR protein complex is required for regulating proteasomal activity and for modulating SOCE, which may contribute to the ciliopathy phenotype

What does inflation really predict?

If the inflaton potential has multiple minima, as may be expected in, e.g., the string theory "landscape", inflation predicts a probability distribution for the cosmological parameters describing spatial curvature (Omega_tot), dark energy (rho_Lambda, w, etc.), the primordial density fluctuations (Omega_tot, dark energy (rho_Lambda, w, etc.). We compute this multivariate probability distribution for various classes of single-field slow-roll models, exploring its dependence on the characteristic inflationary energy scales, the shape of the potential V and and the choice of measure underlying the calculation. We find that unless the characteristic scale Delta-phi on which V varies happens to be near the Planck scale, the only aspect of V that matters observationally is the statistical distribution of its peaks and troughs. For all energy scales and plausible measures considered, we obtain the predictions Omega_tot ~ 1+-0.00001, w=-1 and rho_Lambda in the observed ballpark but uncomfortably high. The high energy limit predicts n_s ~ 0.96, dn_s/dlnk ~ -0.0006, r ~ 0.15 and n_t ~ -0.02, consistent with observational data and indistinguishable from eternal phi^2-inflation. The low-energy limit predicts 5 parameters but prefers larger Q and redder n_s than observed. We discuss the coolness problem, the smoothness problem and the pothole paradox, which severely limit the viable class of models and measures. Our findings bode well for detecting an inflationary gravitational wave signature with future CMB polarization experiments, with the arguably best-motivated single-field models favoring the detectable level r ~ 0.03. (Abridged)Comment: Replaced to match accepted JCAP version. Improved discussion, references. 42 pages, 17 fig

Diet and Physical Activity for the Prevention of Noncommunicable Diseases in Low- and Middle-Income Countries: A Systematic Policy Review

Background: Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low-and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time. Methods and Findings: We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers. Conclusions: This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

Diphenylamine-substituted osmanaphthalyne complexes: structural, bonding, and redox properties of unusual donor–bridge–acceptor systems

Diarylamine-substituted osmanaphthalyne complexes that feature two redox centers linked by the rigid skeleton of the metallacycle (C^C+), specifically, [OsCl2(PPh3)2{(C^C+)NAr2}][BF4 ] (Ar=Ph (1 a), p-MeOPh (1 b)) and their open-ring precursors [OsHCl2(PPh3)2{(CC(PPh3 +)= CHPh)NR2}][BF4 ] (Ar=Ph (2 a), p-MeOPh (2 b)), were successfully synthesized and characterized by 1 H, 13C, and 31P NMR spectroscopy, ESI-MS, and elemental analysis. The solid-state molecular structures of complexes 1 a and 2 a were ascertained by single-crystal X-ray diffraction. The OsC bond length in both complexes 1 a and 2 a fell within the range reported for similar osmanaphthalynes and osmium carbyne complexes, respectively. The structural parameters determined for complex 1 a, which were successfully reproduced by theoretical calculations, point to a p-delocalized metallacycle structure. The purple color of compounds 1 a and b was explained by the diarylamine!Os(metallacycle) chargetransfer absorption in the visible region. The neutral, oneelectron-oxidized and one-electron-reduced states of compounds 1 a, b, and a reference complex that lacked the diarylamine substituent, [OsCl2(PPh3)2{(C^C+)}][BF4] (1’), were investigated by cyclic and square-wave voltammetry, UV/Vis/NIR spectroelectrochemistry, and DFT calculations. The spin density in singly oxidized complexes [1 a]+ and [1 b]+ predominantly resided on the aminyl segment, with osmium involvement controlled by the diphenylamine substitution. Spin density in stable, singly-reduced [1’] was distributed mainly over the osmanaphthalyne metallacycle

Bone Marrow Transplantation for Feline Mucopolysaccharidosis I

Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107–1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-l-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT