A low-rank matrix equation method for solving PDE-constrained optimization problems

PDE-constrained optimization problems arise in a broad number of applications such as hyperthermia cancer treatment and blood flow simulation. Discretization of the optimization problem and using a Lagrangian approach result in a large-scale saddle-point system, which is challenging to solve, and acquiring a full space-time solution is often infeasible. We present a new framework to efficiently compute a low-rank approximation to the solution by reformulating the KKT system into a Sylvester-like matrix equation. This matrix equation is subsequently projected onto a small subspace via an iterative rational Krylov method, and we obtain a reduced problem by imposing a Galerkin condition on its residual. In our work we discuss implementation details and dependence on the various problem parameters. Numerical experiments illustrate the performance of the new strategy also when compared to other low-rank approaches

Clustered alignments of gene-expression time series data

Motivation: Characterizing and comparing temporal gene-expression responses is an important computational task for answering a variety of questions in biological studies. Algorithms for aligning time series represent a valuable approach for such analyses. However, previous approaches to aligning gene-expression time series have assumed that all genes should share the same alignment. Our work is motivated by the need for methods that identify sets of genes that differ in similar ways between two time series, even when their expression profiles are quite different

From a fossil-fuel to a biobased economy : the politics of industrial biotechnology

Industrial biotechnology involves the replacement of petrochemical processes and inputs with more energy-efficient and renewable biological ones. It is already being used in the production of biofuels and bioplastics and has been touted as a means by which modern economies can be shifted toward a more competitive, low-carbon growth model. This paper does two things. First, it outlines the policy framework established in the European Union and the narrative of a knowledge-based bioeconomy (KBBE) underpinning this. Second, it argues that the ‘win – win’ rhetoric contained within the KBBE narrative is misleading. Among the different groups commenting on the use of industrial biotechnology, the paper locates cleavages between farmers and agribusiness, between those convinced and those sceptical of environmental technofixes, and between procorporate and anticorporate NGOs. Taken together, they show the purported transition from a fossil-fuel to a bio-based economy to be a resolutely political one

Genetic relationship between longevity and objectively or subjectively assessed performance traits in sheep using linear censored models

Genetic parameters of longevity in crossbred mule ewes, and genetic relationships among longevity, growth, body composition, and subjectively assessed traits on mule lambs and ewes have been estimated using Bayesian linear censored models. Additionally, the genetic associations between longevity and culling reasons were examined. Data comprised 1,797 observations of mule ewes for longevity, culling reasons, growth, body composition, mouth scores, and type traits. Longevity was defined as the time (in years) from 2 yr of age (the age at first lambing of most ewes) to culling or death. Censored data (i.e., observations for which only the lower bound of the true longevity is known, such as when the animals are still alive) comprised 24% of all observations for longevity. Bivariate analyses were used to analyze the longevity of the ewe with each performance trait by fitting linear Bayesian models considering censored observations. Longevity was split into 3 different sub-traits: age at culling due to teeth/mouth conditions, age at culling due to udder conditions, and age at culling due to other culling reasons. These sub-traits and their aggregation into the overall trait of longevity were analyzed in a multiple-trait model. The heritability of longevity was moderate at 0.27, whereas heritabilities of the growth and body composition traits ranged from 0.11 for average of shoulder, loin, and gigot conformation to 0.36 for ewe BW at first premating. Mouth scores and type traits had heritabilities ranging from 0.13 for jaw position to 0.39 for fleece quality. All analyzed traits showed low genetic correlations with longevity, ranging from –0.20 for average conformation scores in live animals to 0.18 for tooth angle. Teeth/mouth conditions resulted in the greatest heritability (0.15) among the sub-traits based on the separate culling reasons. Genetic correlations between separate culling reasons were low to high (0.12 to 0.63 for teeth/mouth conditions with udder conditions and other culling reasons, respectively). Longevity may be preferred as a selection criterion because of (i) its moderate heritability compared with its component sub-traits based on specific culling reasons, and (ii) its moderate to high genetic correlation with these component sub-traits. The moderate heritability for longevity reflects the potential of this trait for genetic improvement, especially when longevity is based on clearly defined culling reasons

Index selection in terminal sires improves lamb performance at finishing

Lamb meat is often perceived by consumers as fatty, and consumption has decreased in recent decades. A lean growth index was developed in the UK for terminal sire breeds to increase carcass lean content and constrain fat content at a constant age end point. The purposes of this study were 1) to evaluate the effects of index selection of terminal sires on their crossbred offspring at finishing and 2) to evaluate its effectiveness within terminal sire breeds. Approximately 70% of lambs marketed in the UK have been sired by rams of breeds typically thought of as specialized terminal sires. The most widely used are Charollais, Suffolk, and Texel. These breeds participated in sire referencing schemes from the early 1990s by sharing rams among flocks selected on the lean growth index. From 1999 to 2002 approximately 15 “high” and 15 “low” lean growth index score rams were selected from within their sire referencing schemes and mated to Welsh and Scottish Mule ewes. Their crossbred offspring were commercially reared on 3 farms in the UK. Lambs were finished to an estimated 11% subcutaneous fat by visual evaluation. At finishing, lambs were weighed, ultrasonically scanned, and assessed for condition score and conformation. Records were obtained for 6,356 lambs on finishing BW (FWT), ultrasonic muscle depth (UMD), ultrasonic fat depth, overall condition score (OCS), and conformation of gigot, loin, and shoulder. Ultrasonic fat depth was log transformed (logUFD) to approach normality. High-index-sired lambs were heavier at finishing (1.2 ± 0.2 kg) with thicker UMD (0.7 ± 0.2 mm) and less logUFD (0.08 ± 0.01 mm; P \u3c 0.05). There were no differences in OCS or conformation based on the sire index or breed (P \u3e 0.08). Suffolk-sired lambs were heavier than Charollais (1.0 ± 0.3 kg), which were heavier than Texel (0.9 ± 0.3 kg; P \u3c 0.001). Texel-sired lambs had thicker UMD than Charollais (0.7 ± 0.2 mm; P \u3c 0.001) but were not different than Suffolk. Charollais-sired lambs had greater logUFD than both Texel (0.098 ± 0.016 mm) and Suffolk (0.061 ± 0.017 mm) sired lambs (P \u3c 0.001). Within a breed, high- and low-index-sired lambs differed in performance with the exceptions of FWT and UMD in Suffolks. Index selection produced heavier and leaner lambs at finishing. Producers have flexibility in choosing the terminal sire that best fits their production system

Index selection in terminal sires improves early lamb growth

The use of terminal sires (TS) for crossbreeding is integral to the UK sheep industry where approximately 71% of market lambs are sired by TS rams. Early growth of these crossbred lambs affects profitability. The objectives of this study were i) to evaluate the effectiveness of index selection among TS on BW and ADG of their crossbred offspring; and ii) to compare the efficacy of that selection within TS breeds. The most widely used TS breeds in the United Kingdom are Charollais, Suffolk, and Texel. These participated in sire referencing schemes in which they were evaluated on a lean growth index designed to increase carcass lean weight at a given age. From 1999 to 2002, approximately 15 high and 15 low lean growth index rams per breed (93 in total, differing in index on average by 4.6 SD) were selected from within their sire referencing schemes and mated to Welsh and Scottish Mule ewes. Their crossbred offspring were reared commercially on 3 experimental farms in England, Scotland, and Wales. A total of 6,515 lambs were born between 2000 and 2003. Lambs were weighed at birth (BWT), 5 wk (5WT), and 10 wk (10WT), and their ADG from birth to 10 wk was calculated. Lambs sired by high index rams were on average, across breeds, heavier at all ages (P \u3c 0.01) with 0.07 ± 0.03, 0.3 ± 0.1, and 0.4 ± 0.1 kg greater BWT, 5WT, and 10WT, respectively. Their ADG was 5.1 ± 1.9 g/d greater than low-index-sired lambs (P \u3c 0.01). Suffolk-sired lambs were on average heavier at all ages, with greater ADG, whereas Charollais-sired lambs were lightest with smallest ADG. Overall, there was no significant interaction between sire index and sire breed (P \u3e 0.10). Within Suffolk-sired lambs, there was little difference between high and low index sires for the traits studied (P \u3e 0.3). High and low index Charollais-sired lambs differed in BWT (0.09 ± 0.04 kg) and 5WT (0.3 ± 0.1 kg), and Texel-sired lambs differed in 5WT (0.5 ± 0.1 kg), 10WT (0.9 ± 0.2 kg), and ADG (10.2 ± 3.3 g/d; P \u3c 0.01). Lambs from Scottish Mule dams were heavier, with greater ADG, than lambs born to Welsh Mules (P \u3c 0.01). Lambs reared in Scotland were heavier at all ages (P \u3c 0.01). The results suggest that using index selection in TS can improve the growth of their commercial offspring reared on grass

Drug-Associated Changes in Amino Acid Residues in Gag p2, p7\u3csup\u3eNC\u3c/sup\u3e, and p6\u3csup\u3eGag\u3c/sup\u3e/p6\u3csup\u3ePol\u3c/sup\u3e in Human Immunodeficiency Virus Type 1 (HIV-1) Display a Dominant Effect on Replicative Fitness and Drug Response

Regions of HIV-1 gag between p2 and p6Gag/p6Pol, in addition to protease (PR), develop genetic diversity in HIV-1 infected individuals who fail to suppress virus replication by combination protease inhibitor (PI) therapy. To elucidate functional consequences for viral replication and PI susceptibility by changes in Gag that evolve in vivo during PI therapy, a panel of recombinant viruses was constructed. Residues in Gag p2/p7NC cleavage site and p7NC, combined with residues in the flap of PR, defined novel fitness determinants that restored replicative capacity to the posttherapy virus. Multiple determinants in Gag have a dominant effect on PR phenotype and increase susceptibility to inhibitors of drug-resistant or drug-sensitive PR genes. Gag determinants of drug sensitivity and replication alter the fitness landscape of the virus, and viral replicative capacity can be independent of drug sensitivity. The functional linkage between Gag and PR provides targets for novel therapeutics to inhibit drug-resistant viruses

Sensitivity analysis of circadian entrainment in the space of phase response curves

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations.Comment: 22 pages, 8 figures. Correction of a mistake in Definition 2.1. arXiv admin note: text overlap with arXiv:1206.414

Drug-associated changes in amino acid residues in Gag p2, p7NC, and p6Gag/p6Pol in human immunodeficiency virus type 1 (HIV-1) display a dominant effect on replicative fitness and drug response

AbstractRegions of HIV-1 gag between p2 and p6Gag/p6Pol, in addition to protease (PR), develop genetic diversity in HIV-1 infected individuals who fail to suppress virus replication by combination protease inhibitor (PI) therapy. To elucidate functional consequences for viral replication and PI susceptibility by changes in Gag that evolve in vivo during PI therapy, a panel of recombinant viruses was constructed. Residues in Gag p2/p7NC cleavage site and p7NC, combined with residues in the flap of PR, defined novel fitness determinants that restored replicative capacity to the posttherapy virus. Multiple determinants in Gag have a dominant effect on PR phenotype and increase susceptibility to inhibitors of drug-resistant or drug-sensitive PR genes. Gag determinants of drug sensitivity and replication alter the fitness landscape of the virus, and viral replicative capacity can be independent of drug sensitivity. The functional linkage between Gag and PR provides targets for novel therapeutics to inhibit drug-resistant viruses

Genetic evaluation of days to harvest in crossbred lambs

Days to harvest (DTH) is the number of days a lamb is fed before reaching a target level of fatness. Although economically relevant, this trait has not been thoroughly evaluated in sheep. Most lambs harvested in the United Kingdom are crossbreds sired by purebred terminal sires, with Charollais, Suffolk, and Texel most commonly used. Sires from these breeds were selected on an index designed to increase lean growth while constraining fat. The purpose of this research was to 1) evaluate the effects of index selection in terminal sires on DTH and 2) evaluate the feasibility of incorporating DTH into genetic evaluation programs. Charollais, Suffolk, and Texel sheep had participated in sire referencing schemes where genetic links among flocks were established by sharing rams. Rams with high or low index scores were chosen from these schemes and mated to crossbred ewes at 3 farms in the United Kingdom. Lambs were harvested at a target 11% subcutaneous fat. Records on DTH from 6,350 lambs were analyzed in 2 ways: 1) as time to harvest fitting a survival model and 2) as a normally distributed variable in a bivariate analysis with weight at harvest. The survival analysis was stratified by rearing type (single or twin). In both approaches, sires were fitted using a multivariate normal distribution with a relationship matrix. Regardless of model fitted, sire index did not affect DTH (P \u3e 0.10). However, Texel-sired lambs reached harvest faster (P \u3c 0.01) than either Charollais- or Suffolk-sired lambs although DTH in those 2 breed types did not differ (P \u3e 0.1). Ewe lambs reached harvest faster than wethers (P \u3c 0.01). Lambs from older ewes were harvested faster (P \u3c 0.001). The heritability of DTH was 0.21 from the survival model and 0.20 from the bivariate model. Rank correlation of sire EBV between methods was 0.9, suggesting strong agreement. The use of high or low index sires did not extend DTH in lambs harvested at a target fatness. Importantly, there is no antagonism between improving carcass merit and extending the grazing season. Furthermore, DTH is moderately heritable. If economically justified within a breeding program, it could be reduced through genetic selection