Cross-validation for change-point regression: Pitfalls and solutions

Cross-validation is the standard approach for tuning parameter selection in many non-parametric regression problems. However its use is less common in change-point regression, perhaps as its prediction error-based criterion may appear to permit small spurious changes and hence be less well-suited to estimation of the number and location of change-points. We show that in fact the problems of cross-validation with squared error loss are more severe and can lead to systematic under- or over-estimation of the number of change-points, and highly suboptimal estimation of the mean function in simple settings where changes are easily detectable. We propose two simple approaches to remedy these issues, the first involving the use of absolute error rather than squared error loss, and the second involving modifying the holdout sets used. For the latter, we provide conditions that permit consistent estimation of the number of change-points for a general change-point estimation procedure. We show these conditions are satisfied for optimal partitioning using new results on its performance when supplied with the incorrect number of change-points. Numerical experiments show that the absolute error approach in particular is competitive with common change-point methods using classical tuning parameter choices when error distributions are well-specified, but can substantially outperform these in misspecified models. An implementation of our methodology is available in the R package crossvalidationCP on CRAN

A Framework for Improving the Sharing of Manufacturing Knowledge through Micro-Blogging

The purpose of this paper is to report on an industrial investigation, conducted within a leading power generation manufacturer, to better understand the organisational processes and challenges present in relation to the management and sharing of knowledge during product manufacturing. Findings reveal that the organisation is failing to fully benefit from web 2.0 technologies and particularly micro-blogging. Details of the investigation results are presented and a conceptual framework is proposed to demonstrate how organisations may enhance the sharing of explicit manufacturing knowledge using micro-blogging tools

Influence of uniaxial tensile stress on the mechanical and piezoelectric properties of short-period ferroelectric superlattice

Tetragonal ferroelectric/ferroelectric BaTiO3/PbTiO3 superlattice under uniaxial tensile stress along the c axis is investigated from first principles. We show that the calculated ideal tensile strength is 6.85 GPa and that the superlattice under the loading of uniaxial tensile stress becomes soft along the nonpolar axes. We also find that the appropriately applied uniaxial tensile stress can significantly enhance the piezoelectricity for the superlattice, with piezoelectric coefficient d33 increasing from the ground state value by a factor of about 8, reaching 678.42 pC/N. The underlying mechanism for the enhancement of piezoelectricity is discussed

Spliceosome-mediated decay (SMD) regulates expression of nonintronic genes in budding yeast

We uncovered a novel role for the spliceosome in regulating mRNA expression levels that involves splicing coupled to RNA decay, which we refer to as spliceosome-mediated decay (SMD). Our transcriptome-wide studies identified numerous transcripts that are not known to have introns but are spliced by the spliceosome at canonical splice sites in Saccharomyces cerevisiae. Products of SMD are primarily degraded by the nuclear RNA surveillance machinery. We demonstrate that SMD can significantly down-regulate mRNA levels; splicing at canonical splice sites in the bromodomain factor 2 (BDF2) transcript reduced transcript levels roughly threefold by generating unstable products that are rapidly degraded by the nuclear surveillance machinery. Regulation of BDF2 mRNA levels by SMD requires Bdf1, a functionally redundant Bdf2 paralog that plays a role in recruiting the spliceosome to the BDF2 mRNA. Interestingly, mutating BDF2 5' splice site and branch point consensus sequences partially suppresses the bdf1Δ temperature-sensitive phenotype, suggesting that maintaining proper levels of Bdf2 via SMD is biologically important. We propose that the spliceosome can also repress protein-coding gene expression by promoting nuclear turnover of spliced RNA products and provide an insight for coordinated regulation of Bdf1 and Bdf2 levels in the cell

Loss of the RNA polymerase III repressor MAF1 confers obesity resistance.

MAF1 is a global repressor of RNA polymerase III transcription that regulates the expression of highly abundant noncoding RNAs in response to nutrient availability and cellular stress. Thus, MAF1 function is thought to be important for metabolic economy. Here we show that a whole-body knockout of Maf1 in mice confers resistance to diet-induced obesity and nonalcoholic fatty liver disease by reducing food intake and increasing metabolic inefficiency. Energy expenditure in Maf1(-/-) mice is increased by several mechanisms. Precursor tRNA synthesis was increased in multiple tissues without significant effects on mature tRNA levels, implying increased turnover in a futile tRNA cycle. Elevated futile cycling of hepatic lipids was also observed. Metabolite profiling of the liver and skeletal muscle revealed elevated levels of many amino acids and spermidine, which links the induction of autophagy in Maf1(-/-) mice with their extended life span. The increase in spermidine was accompanied by reduced levels of nicotinamide N-methyltransferase, which promotes polyamine synthesis, enables nicotinamide salvage to regenerate NAD(+), and is associated with obesity resistance. Consistent with this, NAD(+) levels were increased in muscle. The importance of MAF1 for metabolic economy reveals the potential for MAF1 modulators to protect against obesity and its harmful consequences

Effects of repleting organic phosphates in banked erythrocytes on plasma metabolites and vasoactive mediators after red cell exchange transfusion in sickle cell disease

Background - Red blood cell (RBC) exchange (RCE) transfusion therapy is indicated for certain patients with sickle cell disease (SCD). Although beneficial, this therapy is costly and inconvenient to patients, who may require it monthly or more often. Identification of blood and plasma biomarkers that could improve or help individualise RCE therapy is of interest. Here we examined relevant blood and plasma metabolites and biomarkers of vasoactivity and RBC fragility in a pilot study of SCD patients undergoing RCE using either standard RBC units or RBC units treated with a US Food and Drug Administration (FDA)-approved additive solution containing phosphate, inosine, pyruvate, and adenine ("PIPA"). Materials and methods - In this prospective, single-blind, cross-over pilot clinical trial, patients were randomised to receive either standard RBC exchange or PIPA-treated RBC exchange transfusion with each RCE session over a 6-month treatment period. Pre- and post-transfusion blood samples were obtained and analysed for RBC O2 affinity, ATP, purine metabolites, RBC microparticles, and cell free haemoglobin. Results - Red blood cell O2 affinity was maintained after PIPA-RCE in contrast to standard RCE, after which P50 fell (net O2 affinity rose). Plasma ATP did not change significantly after RCE using either of the RBC unit types. Exchange transfusion with PIPA-treated RBC units led to modest increases in plasma inosine and hypoxanthine. Plasma cell free haemoglobin fell after either standard or PIPA-treated RBC exchange transfusion (novel findings), and to a similar extent. RBC-derived microparticles in the plasma fell significantly and similarly after both standard and PIPA-treated RCE transfusion. Discussion - In summary, treatment of RBCs with PIPA prior to RCE elicited favourable or neutral changes in key metabolic and vascular biomarkers. Further study of its efficacy and safety is recommended and could ultimately serve to improve outcomes in chronically transfused SCD patients

The Labour of Love: Seasonal Migration from Jharkhand to the Brick Kilns of Other States in India

Seasonal casual labour migration in India has conventionally been understood as the result of extreme poverty whereby villagers are forced to become migrants for the dry six months to subsist or merely survive. This article draws on fieldwork in a village in Jharkhand and a brick kiln in West Bengal to argue that migrants do not understand their movement in economic terms alone. Many see the brick kilns as a temporary space of freedom to escape problems back home, explore a new country, gain independence from parents or live out prohibited amorous relationships. It is suggested that Jharkhandi activists and policy-makers’ construction of such migration as a ‘problem’ is as much about their vision of how the new tribal state ought to be as about exploitation. Migration to the kilns is seen by them as a threat to the purity and regulation of the social and sexual tribal citizen. This moralising perspective creates a climate that paradoxically encourages many young people to flee to the brick kilns where they can live ‘freely’. In this way, the new puritanism at home helps to reproduce the conditions for capitalist exploitation and the extraction of surplus value

The role of cytokine gene polymorphisms in the pathogenesis of abdominal aortic aneurysms: A case-control study

AbstractBackground: Cytokines are the primary mediators of inflammation and also influence matrix metalloproteinase expression, both of which are important in development of abdominal aortic aneurysm (AAA). A significant, but as yet unknown, familial factor contributes to the pathogenesis of AAA. Many cytokine genes contain polymorphic sites, some of which affect cytokine production in vitro. Cytokine gene polymorphisms may therefore influence the pathogenesis of AAA. The purpose of this study was to determine whether there is any association between cytokine gene polymorphisms and AAA. Methods and Results: This case-control study comprised 100 patients with AAA and 100 age-matched and sex-matched control subjects. For each case and control subject in the study, genotypes at the following cytokine gene polymorphic loci were determined: interleukin (IL)-1β +3953, IL-6 −174, IL-10 −1082, IL-10 −592, and tumor necrosis factors-α −308. Allele and genotype frequencies were compared between AAA and control groups, and odds ratios (OR) were calculated for the presence of AAA with each allele at each locus examined as risk factors. The IL-10 −1082 A allele was significantly more common in the AAA group than the control group (P =.03). The OR for the IL-10 −1082 A allele as a risk factor for AAA was 1.8 (95% confidence interval, 0.9-3.6). Discussion: These associations suggest a significant role for IL-10 in the pathogenesis of AAA. This association of AAA with the IL-10 −1082 A allele is also biologically plausible; the IL-10 −1082 A allele is associated with low IL-10 secretion, and it may be that AAA develops in patients who are unable to mount the same anti-inflammatory response as those who do not have AAA. (J Vasc Surg 2003;37:999-1005.

Local optical spectroscopy of semiconductor nanostructures in the linear regime

We present a theoretical approach to calculate the local absorption spectrum of excitons confined in a semiconductor nanostructure. Using the density-matrix formalism, we derive a microscopic expression for the nonlocal susceptibility, both in the linear and nonlinear regimes, which includes a three-dimensional description of electronic quantum states and their Coulomb interaction. The knowledge of the nonlocal susceptibility allows us to calculate a properly defined local absorbed power, which depends on the electromagnetic field distribution. We report on explicit calculations of the local linear response of excitons confined in single and coupled T-shaped quantum wires with realistic geometry and composition. We show that significant interference effects in the interacting electron-hole wave function induce new features in the space-resolved optical spectra, particularly in coupled nanostructures. When the spatial extension of the electromagnetic field is comparable to the exciton Bohr radius, Coulomb effects on the local spectra must be taken into account for a correct assignment of the observed features

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.