An investigation of using an RQP based method to calculate parameter sensitivity derivatives

Estimation of the sensitivity of problem functions with respect to problem variables forms the basis for many of our modern day algorithms for engineering optimization. The most common application of problem sensitivities has been in the calculation of objective function and constraint partial derivatives for determining search directions and optimality conditions. A second form of sensitivity analysis, parameter sensitivity, has also become an important topic in recent years. By parameter sensitivity, researchers refer to the estimation of changes in the modeling functions and current design point due to small changes in the fixed parameters of the formulation. Methods for calculating these derivatives have been proposed by several authors (Armacost and Fiacco 1974, Sobieski et al 1981, Schmit and Chang 1984, and Vanderplaats and Yoshida 1985). Two drawbacks to estimating parameter sensitivities by current methods have been: (1) the need for second order information about the Lagrangian at the current point, and (2) the estimates assume no change in the active set of constraints. The first of these two problems is addressed here and a new algorithm is proposed that does not require explicit calculation of second order information

An investigation of new methods for estimating parameter sensitivities

The method proposed for estimating sensitivity derivatives is based on the Recursive Quadratic Programming (RQP) method and in conjunction a differencing formula to produce estimates of the sensitivities. This method is compared to existing methods and is shown to be very competitive in terms of the number of function evaluations required. In terms of accuracy, the method is shown to be equivalent to a modified version of the Kuhn-Tucker method, where the Hessian of the Lagrangian is estimated using the BFS method employed by the RQP algorithm. Initial testing on a test set with known sensitivities demonstrates that the method can accurately calculate the parameter sensitivity

Measurement of Branching Fractions and Rate Asymmetries in the Rare Decays B -> K(*) l+ l-

In a sample of 471 million BB events collected with the BABAR detector at the PEP-II e+e- collider we study the rare decays B -> K(*) l+ l-, where l+ l- is either e+e- or mu+mu-. We report results on partial branching fractions and isospin asymmetries in seven bins of di-lepton mass-squared. We further present CP and lepton-flavor asymmetries for di-lepton masses below and above the J/psi resonance. We find no evidence for CP or lepton-flavor violation. The partial branching fractions and isospin asymmetries are consistent with the Standard Model predictions and with results from other experiments.Comment: 16 pages, 14 figures, accepted by Phys. Rev.

Measurement of CP Asymmetries and Branching Fractions in Charmless Two-Body B-Meson Decays to Pions and Kaons

We present improved measurements of CP-violation parameters in the decays $B^0 \to \pi^+ \pi^-$, $B^0 \to K^+ \pi^-$, and $B^0 \to \pi^0 \pi^0$, and of the branching fractions for $B^0 \to \pi^0 \pi^0$ and $B^0 \to K^0 \pi^0$. The results are obtained with the full data set collected at the $\Upsilon(4S)$ resonance by the BABAR experiment at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory, corresponding to $467 \pm 5$ million $B\bar B$ pairs. We find the CP-violation parameter values and branching fractions $S_{\pi^+\pi^-} = -0.68 \pm 0.10 \pm 0.03, C_{\pi^+\pi^-} = -0.25 \pm 0.08 \pm 0.02, A_{K^-\pi^+} = -0.107 \pm 0.016 ^{+0.006}_{-0.004}, C_{\pi^0\pi^0} = -0.43 \pm 0.26 \pm 0.05, Br(B^0 \to \pi^0 \pi^0) = (1.83 \pm 0.21 \pm 0.13) \times 10^{-6}, Br(B^0 \to K^0 \pi^0) = (10.1 \pm 0.6 \pm 0.4) \times 10^{-6},$ where in each case, the first uncertainties are statistical and the second are systematic. We observe CP violation with a significance of 6.7 standard deviations for $B^0 \to\pi^+\pi^-$ and 6.1 standard deviations for $B^0 \to K^+ \pi^-$, including systematic uncertainties. Constraints on the Unitarity Triangle angle $\alpha$ are determined from the isospin relations among the $B \to \pi\pi$ rates and asymmetries. Considering only the solution preferred by the Standard Model, we find $\alpha$ to be in the range $[71^\circ,109^\circ]$ at the 68% confidence level.Comment: 18 pages, 11 postscript figures, submitted to Phys. Rev.

Whole genome sequencing and phylogenetic analysis of strains of the agent of Lyme disease Borrelia burgdorferi from Canadian emergence zones

Lyme disease is emerging in southern Canada due to range expansion of the tick vector, followed by invasion of the agent of Lyme disease Borrelia burgdorferi sensu stricto. Strain diversity, as determined by Multi Locus Sequence Typing, occurs in this zone of emergence, and this may have its origins in adaptation to ecological niches, and have phenotypic consequences for pathogenicity and serological test performance. Sixty-four unique strains were cultured from ticks collected in southern Canada and the genomes sequenced using the Illumina MiSeq platform. A maximum likelihood phylogenetic tree of the chromosome revealed two large clades with multiple subclades. Consistent with previous studies on this species, the clades were not geographically defined, and some Canadian strains were highly divergent from previously sequenced US strains. There was evidence for recombination in the chromosome but this did not affect the phylogeny. Analysis of chromosomal genes indicated that these are under intense purifying selection. Phylogenies of the accessory genome and chromosome were congruent. Therefore strain differences identified in the phylogeny of chromosomal genes likely act as a proxy for genetic determinants of phenotypic differences amongst strains that are harboured in the accessory genome. Further studies on health implications of strain diversity are needed

Environmental controls, oceanography and population dynamics of pathogens and harmful algal blooms: connecting sources to human exposure

© 2008 Author et al. This is an open access article distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Environmental Health 7 (2008): S5, doi:10.1186/1476-069X-7-S2-S5.Coupled physical-biological models are capable of linking the complex interactions between environmental factors and physical hydrodynamics to simulate the growth, toxicity and transport of infectious pathogens and harmful algal blooms (HABs). Such simulations can be used to assess and predict the impact of pathogens and HABs on human health. Given the widespread and increasing reliance of coastal communities on aquatic systems for drinking water, seafood and recreation, such predictions are critical for making informed resource management decisions. Here we identify three challenges to making this connection between pathogens/HABs and human health: predicting concentrations and toxicity; identifying the spatial and temporal scales of population and ecosystem interactions; and applying the understanding of population dynamics of pathogens/HABs to management strategies. We elaborate on the need to meet each of these challenges, describe how modeling approaches can be used and discuss strategies for moving forward in addressing these challenges.The authors acknowledge the financial support for the NSF/NIEHS and NOAA Centers for Oceans and Human Healt

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 x 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 x 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 x 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 x 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 x 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 x 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies

Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.

Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology

Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene

A Precision Measurement of the Lambda_c Baryon Mass

The $\Lambda_c^+$ baryon mass is measured using $\Lambda_c^+\to\Lambda K^0_S K^+$ and $\Lambda_c^+\to\Sigma^0 K^0_S K^+$ decays reconstructed in 232 fb$^{-1}$ of data collected with the BaBar detector at the PEP-II asymmetric-energy $e^+e^-$ storage ring. The $\Lambda_c^+$ mass is measured to be $2286.46\pm0.14\mathrm{MeV}/c^2$. The dominant systematic uncertainties arise from the amount of material in the tracking volume and from the magnetic field strength.Comment: 14 pages, 8 postscript figures, submitted to Phys. Rev.