The Particle Spectrum of Heterotic Compactifications

Techniques are presented for computing the cohomology of stable, holomorphic vector bundles over elliptically fibered Calabi-Yau threefolds. These cohomology groups explicitly determine the spectrum of the low energy, four-dimensional theory. Generic points in vector bundle moduli space manifest an identical spectrum. However, it is shown that on subsets of moduli space of co-dimension one or higher, the spectrum can abruptly jump to many different values. Both analytic and numerical data illustrating this phenomenon are presented. This result opens the possibility of tunneling or phase transitions between different particle spectra in the same heterotic compactification. In the course of this discussion, a classification of SU(5) GUT theories within a specific context is presented.Comment: 77 pages, 3 figure

Socioeconomic Variation in the Prevalence, Introduction, Retention, and Removal of Smoke-Free Policies among Smokers: Findings from the International Tobacco Control (ITC) Four Country Survey

Introduction: Exposure to secondhand smoke causes premature death and disease in non-smokers and indoor smoke-free policies have become increasingly prevalent worldwide. Although socioeconomic disparities have been documented in tobacco use and cessation, the association between socioeconomic status (SES) and smoke-free policies is less well studied. Methods: Data were obtained from the 2006 and 2007 Waves of the International Tobacco Control Four Country Survey (ITC-4), a prospective study of nationally representative samples of smokers in Canada, the United States, the United Kingdom, and Australia. Telephone interviews were administered to 8,245 current and former adult smokers from October 2006 to February 2007. Between September 2007 and February 2008, 5,866 respondents were re-interviewed. Self-reported education and annual household income were used to create SES tertiles. Outcomes included the presence, introduction, and removal of smoke-free policies in homes, worksites, bars, and restaurants. Results: Smokers with high SES had increased odds of both having [OR: 1.54, 95% CI: 1.27–2.87] and introducing [OR: 1.49, 95% CI: 1.04–2.13] a total ban on smoking in the home compared to low SES smokers. Continuing smokers with high SES also had decreased odds of removing a total ban [OR: 0.44, 95% CI: 0.26–0.73]. No consistent association was observed between SES and the presence or introduction of bans in worksites, bars, or restaurants. Conclusions: The presence, introduction, and retention of smoke-free homes increases with increasing SES, but no consistent socioeconomic variation exists in the presence or introduction of total smoking bans in worksites, bars, or restaurants. Opportunities exist to reduce SES disparities in smoke-free homes, while the lack of socioeconomic differences in public workplace, bar, and restaurant smoke-free policies suggest these measures are now equitably distributed in these four countries

Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide

BACKGROUND: N-butylidenephthalide (BP) exhibits antitumor effect in a variety of cancer cell lines. The objective of this study was to obtain additional insights into the mechanisms involved in BP induced cell death in human prostate cancer cells. METHODS/PRINCIPAL FINDINGS: Two human prostate cancer cell lines, PC-3 and LNCaP, were treated with BP, and subsequently evaluated for their viability and cell cycle profiles. BP caused cell cycle arrest and cell death in both cell lines. The G0/G1 phase arrest was correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. To determine the mechanisms of BP-induced growth arrest and cell death in prostate cancer cell lines, we performed a microarray study to identify alterations in gene expression induced by BP in the LNCaP cells. Several BP-induced genes, including the GADD153/CHOP, an endoplasmic reticulum stress (ER stress)-regulated gene, were identified. BP-induced ER stress was evidenced by increased expression of the downstream molecules GRP78/BiP, IRE1-α and GADD153/CHOP in both cell lines. Blockage of IRE1-α or GADD153/CHOP expression by siRNA significantly reduced BP-induced cell death in LNCaP cells. Furthermore, blockage of JNK1/2 signaling by JNK siRNA resulted in decreased expression of IRE1-α and GADD153/CHOP genes, implicating that BP-induced ER stress may be elicited via JNK1/2 signaling in prostate cancer cells. BP also suppressed LNCaP xenograft tumor growth in NOD-SCID mice. It caused 68% reduction in tumor volume after 18 days of treatment. CONCLUSIONS: Our results suggest that BP can cause G0/G1 phase arrest in prostate cancer cells and its cytotoxicity is mediated by ER stress induction. Thus, BP may serve as an anticancer agent by inducing ER stress in prostate cancer

Occupational exposure to magnetic fields and breast cancer among Canadian men

Occupational magnetic field (MF) exposure has been suggested as a risk factor for breast cancer in both men and women. Due to the rarity of this disease in men, most epidemiologic studies investigating this relationship have been limited by small sample sizes. Herein, associations of several measures of occupational MF exposure with breast cancer in men were investigated using data from the population-based case-control component of the Canadian National Enhanced Cancer Surveillance System. Lifetime job histories were provided by 115 cases and 570 controls. Average MF exposure of individual jobs was classified into three categories (<0.3, 0.3 to <0.6, or ≥0.6 μT) through expert blinded review of participant's lifetime occupational histories. The impact of highest average and cumulative MF exposure, as well as exposure duration and specific exposure-time windows, on cancer risk was examined using logistic regression. The proportion of cases (25%) with a highest average exposure of ≥0.3 μT was higher than among controls (22%)

Translocations as Experiments in the Ecological Resilience of an Asocial Mega-Herbivore

Species translocations are remarkable experiments in evolutionary ecology, and increasingly critical to biodiversity conservation. Elaborate socio-ecological hypotheses for translocation success, based on theoretical fitness relationships, are untested and lead to complex uncertainty rather than parsimonious solutions. We used an extraordinary 89 reintroduction and 102 restocking events releasing 682 black rhinoceros (Diceros bicornis) to 81 reserves in southern Africa (1981–2005) to test the influence of interacting socio-ecological and individual characters on post-release survival. We predicted that the socio-ecological context should feature more prominently after restocking than reintroduction because released rhinoceros interact with resident conspecifics. Instead, an interaction between release cohort size and habitat quality explained reintroduction success but only individuals' ages explained restocking outcomes. Achieving translocation success for many species may not be as complicated as theory suggests. Black rhino, and similarly asocial generalist herbivores without substantial predators, are likely to be resilient to ecological challenges and robust candidates for crisis management in a changing world

Endocrine therapy resistant ESR1 variants revealed by genomic characterization of breast cancer derived xenografts

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation

Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study

Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI &gt;28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI &gt;28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.</p

Novel Avian Influenza H7N3 Strain Outbreak, British Columbia

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a novel insertion in the HA0 cleavage site of the human and HPAI isolate. This insertion likely occurred by recombination between the hemagglutination and matrix genes in the LPAI virus