From Permanence to Total Availability: A Quantum Conceptual Upgrade

We consider the classical concept of time of permanence and observe that its quantum equivalent is described by a bona fide self-adjoint operator. Its interpretation, by means of the spectral theorem, reveals that we have to abandon not only the idea that quantum entities would be characterizable in terms of spatial trajectories but, more generally, that they would possess the very attribute of spatiality. Consequently, a permanence time shouldn’t be interpreted as a “time” in quantum mechanics, but as a measure of the total availability of a quantum entity in participating to a process of creation of a spatial localization.     

Change in living arrangements following death of a partner in England and Wales, 1971 to 2001

Understanding trends and changes in the circumstances of couples separated by death is important for policy initiatives to reduce vulnerabilities associated with end of life care and for those who live on. This article uses widow(er)hood statistics and census data from the Office for National Statistics Longitudinal Study. It examines changes in couples' living arrangements and households at four successive censuses from 1971 to 2001 and shows how these differ by age and gender on the death of a spouse or partner. Findings draw attention to the effects of ageing and mortality improvements as well as wider social and economic trends in family and household formation, residential independence in older age, and policy developments on long-term care provision for older people.     

Changes in family structure in early childhood in the Millennium Cohort Study

This article develops a typology of family change over the first five years of children's lives using data from the Millennium Cohort Study. It examines the changes over time of parental living arrangements and describes a range of social, economic and well-being indicators. It shows that nearly three quarters of this sample of young children have not experienced changes in family structures. The most advantaged group appears to be children living with continuously married parents, followed by those who live with cohabiting parents who marry. Children who experienced changes in family structure are a diverse group. Coupled parents who separate suffer the largest drop in income over five years. Lone parents who partner gain the most income. However, their incomes are still much lower than continuously partnered parents. This article suggests that using static or overly simplified measures of family structure hides important variations in the experiences of children.     

Ablation of kallikrein 7 (KLK7) in adipose tissue ameliorates metabolic consequences of high fat diet-induced obesity by counteracting adipose tissue inflammation in vivo

Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function. Therefore, we have inactivated the Klk7 gene in adipose tissue using conditional gene-targeting strategies in mice. Klk7-deficient mice (ATKlk7 ^?/?) exhibited less weight gain, predominant expansion of subcutaneous adipose tissue and improved whole body insulin sensitivity under a high fat diet (HFD). ATKlk7 ^?/? mice displayed higher energy expenditure and food intake, most likely due to altered adipokine secretion including lower circulating leptin. Pro-inflammatory cytokine expression was significantly reduced in combination with an increased percentage of alternatively activated (anti-inflammatory) M2 macrophages in epigonadal adipose tissue of ATKlk7 ^?/?. Taken together, by attenuating adipose tissue inflammation, altering adipokine secretion and epigonadal adipose tissue expansion, Klk7 deficiency in adipose tissue partially ameliorates the adverse effects of HFD-induced obesity. In summary, we provide first evidence for a previously unrecognized role of KLK7 in adipose tissue with effects on whole body energy expenditure and insulin sensitivity.     

Deletions and epimutations affecting the human 14q32.2 imprinted region in individuals with paternal and maternal upd(14)-like phenotypes

Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1 and maternally expressed genes (MEGs) such as MEG3 (also known as GTL2), RTL1as (RTL1 antisense) and MEG8 (refs. 1,2), together with the intergenic differentially methylated region (IG-DMR) and the MEG3-DMR. Consistent with this, paternal and maternal uniparental disomy for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. We studied eight individuals (cases 1-8) with a upd(14)pat-like phenotype and three individuals (cases 9-11) with a upd(14)mat-like phenotype in the absence of upd(14) and identified various deletions and epimutations affecting the imprinted region. The results, together with recent mouse data, imply that the IG-DMR has an important cis-acting regulatory function on the maternally inherited chromosome and that excessive RTL1 expression and decreased DLK1 and RTL1 expression are relevant to upd(14)pat-like and upd(14)mat-like phenotypes, respectively.     

NAD(P)H:quinone oxidoreductase 1 NQO1*2 genotype (P187S) is a strong prognostic and predictive factor in breast cancer

NQO1 guards against oxidative stress and carcinogenesis and stabilizes p53. We find that a homozygous common missense variant (NQO1(*)2, rs1800566(T), NM_000903.2:c.558C>T) that disables NQO1 strongly predicts poor survival among two independent series of women with breast cancer (P = 0.002, N = 1,005; P = 0.005, N = 1,162), an effect particularly evident after anthracycline-based adjuvant chemotherapy with epirubicin (P = 7.52 x 10(-6)) and in p53-aberrant tumors (P = 6.15 x 10(-5)). Survival after metastasis was reduced among NQO1(*)2 homozygotes, further implicating NQO1 deficiency in cancer progression and treatment resistance. Consistently, response to epirubicin was impaired in NQO1(*)2-homozygous breast carcinoma cells in vitro, reflecting both p53-linked and p53-independent roles of NQO1. We propose a model of defective anthracycline response in NQO1-deficient breast tumors, along with increased genomic instability promoted by elevated reactive oxygen species (ROS), and suggest that the NQO1 genotype is a prognostic and predictive marker for breast cancer.