Altered pathways in methylome and transcriptome longitudinal analysis of normal weight and bariatric surgery women

DNA methylation could provide a link between environmental, genetic factors and weight control and can modify gene expression pattern. This study aimed to identify genes, which are differentially expressed and methylated depending on adiposity state by evaluating normal weight women and obese women before and after bariatric surgery (BS). We enrolled 24 normal weight (BMI: 22.5 +/- 1.6 kg/m(2)) and 24 obese women (BMI: 43.3 +/- 5.7 kg/m(2)) submitted to BS. Genome-wide methylation analysis was conducted using Infinium Human Methylation 450 BeadChip (threshold for significant CpG sites based on delta methylation level with a minimum value of 5%, a false discovery rate correction (FDR) of q /=2.0 was used to detect differentially expressed probes). The integrative analysis of both array data identified four genes (i.e. TPP2, PSMG6, ARL6IP1 and FAM49B) with higher methylation and lower expression level in pre-surgery women compared to normal weight women: and two genes (i.e. ZFP36L1 and USP32) that were differentially methylated after BS. These methylation changes were in promoter region and gene body. All genes are related to MAPK cascade, NIK/NF-kappaB signaling, cellular response to insulin stimulus, proteolysis and others. Integrating analysis of DNA methylation and gene expression evidenced that there is a set of genes relevant to obesity that changed after BS. A gene ontology analysis showed that these genes were enriched in biological functions related to adipogenesis, orexigenic, oxidative stress and insulin metabolism pathways. Also, our results suggest that although methylation plays a role in gene silencing, the majority of effects were not correlated

Gas Dynamics and Star Formation in the Galaxy Pair NGC1512/1510

(abridged) Here we present HI line and 20-cm radio continuum data of the nearby galaxy pair NGC1512/1510 as obtained with the Australia Telescope Compact Array. These are complemented by GALEX UV-, SINGG Halpha- and Spitzer mid-infrared images, allowing us to compare the distribution and kinematics of the neutral atomic gas with the locations and ages of the stellar clusters within the system. For the barred, double-ring galaxy NGC1512 we find a very large HI disk, about 4x its optical diameter, with two pronounced spiral/tidal arms. Both its gas distribution and the distribution of the star-forming regions are affected by gravitational interaction with the neighbouring blue compact dwarf galaxy NGC1510. The two most distant HI clumps, at radii of about 80 kpc, show signs of star formation and are likely tidal dwarf galaxies. Star formation in the outer disk of NGC1512 is revealed by deep optical- and two-color ultraviolet images. Using the latter we determine the properties of about 200 stellar clusters and explore their correlation with dense HI clumps in the even larger 2XHI disk. The multi-wavelength analysis of the NGC1512/1510 system, which is probably in the first stages of a minor merger having started about 400 Myr ago, links stellar and gaseous galaxy properties on scales from one to 100 kpc.Comment: accepted in MNRAS (please find the high-resolution pdf file and further information at http://www.atnf.csiro.au/people/bkoribal/ngc1512

Detection and dynamics of circulating tumor cells in patients with high-risk prostate cancer treated with radiotherapy and hormones: a prospective phase II study

BACKGROUND: Circulating tumor cells (CTCs) are an established prognostic marker in castration-resistant prostate cancer but have received little attention in localized high-risk disease. We studied the detection rate of CTCs in patients with high-risk prostate cancer before and after androgen deprivation therapy and radiotherapy to assess its value as a prognostic and monitoring marker. PATIENTS AND METHODS: We performed a prospective analysis of CTCs in the peripheral blood of 65 treatment-naive patients with high-risk prostate cancer. EpCAM-positive CTCs were enumerated using the CELLSEARCH system at 4 timepoints. A cut off of 0 vs >/= 1 CTC/7.5 ml blood was defined as a threshold for negative versus positive CTCs status. RESULTS: CTCs were detected in 5/65 patients (7.5%) at diagnosis, 8/62 (12.9%) following neoadjuvant androgen deprivation and 11/59 (18.6%) at the end of radiotherapy, with a median CTC count/7.5 ml of 1 (range, 1-136). Only 1 patient presented a positive CTC result 9 months after radiotherapy. Positive CTC status (at any timepoint) was not significantly associated with any clinical or pathologic factors. However, when we analyzed variations in CTC patterns following treatment, we observed a significant association between conversion of CTCs and stages T3 (P = 0.044) and N1 (P = 0.002). Detection of CTCs was not significantly associated with overall survival (P > 0.40). CONCLUSIONS: Our study showed a low detection rate for CTCs in patients with locally advanced high-risk prostate cancer. The finding of a de novo positive CTC count after androgen deprivation therapy is probably due to a passive mechanism associated with the destruction of the tumor. Further studies with larger samples and based on more accurate detection of CTCs are needed to determine the potential prognostic and therapeutic value of this approach in non-metastatic prostate cancer. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01800058

Plan de negocio para el desarrollo de una empresa que brinde servicio educativo del idioma ingl?s basado en tecnolog?a de realidad virtual, Inteligencia artificial y Machine Learning

En el Per? hemos evidenciado una falta de capacitaci?n en el idioma ingl?s a pesar de existir un mercado en educaci?n que genera m?s de US$ 50 millones de d?lares en Lima. Es en este escenario que identificamos una oportunidad de negocio. En esta tesis proponemos un plan de negocio para la creaci?n de IVET por sus siglas en ingl?s ?Innovative Virtual English Tutor? empresa dedicada a la capacitaci?n de idioma ingl?s con el uso de realidad virtual, inteligencia artificial y machine learning. Nuestra propuesta de valor es una aplicaci?n educativa que permitir? aprender ingl?s de forma inmersiva con escenarios que propongan al estudiante ciertos retos a superar y lograr aprendizaje. Adem?s, te propondr? una ruta a seguir basado en tus gustos o preferencias y la realizaci?n de escenarios y temas en base a las debilidades detectadas en cada evaluaci?n. Este proyecto ha tomado un enfoque de desarrollo h?brido, en la primera etapa del proyecto y para validar la idea se utiliz? la metodolog?a Lean Startup y luego un estudio de mercado junto a planes complementarios donde podemos mencionar el de marketing, operaciones, TI, recursos humanos, financiero, etc

Identification of a novel synthetic lethal vulnerability in non-small cell lung cancer by co-targeting TMPRSS4 and DDR1

Finding novel targets in non-small cell lung cancer (NSCLC) is highly needed and identification of synthetic lethality between two genes is a new approach to target NSCLC. We previously found that TMPRSS4 promotes NSCLC growth and constitutes a prognostic biomarker. Here, through large-scale analyses across 5 public databases we identified consistent co-expression between TMPRSS4 and DDR1. Similar to TMPRSS4, DDR1 promoter was hypomethylated in NSCLC in 3 independent cohorts and hypomethylation was an independent prognostic factor of disease-free survival. Treatment with 5-azacitidine increased DDR1 levels in cell lines, suggesting an epigenetic regulation. Cells lacking TMPRSS4 were highly sensitive to the cytotoxic effect of the DDR1 inhibitor dasatinib. TMPRSS4/DDR1 double knock-down (KD) cells, but not single KD cells suffered a G0/G1 cell cycle arrest with loss of E2F1 and cyclins A and B, increased p21 levels and a larger number of cells in apoptosis. Moreover, double KD cells were highly sensitized to cisplatin, which caused massive apoptosis (~40%). In vivo studies demonstrated tumor regression in double KD-injected mice. In conclusion, we have identified a novel vulnerability in NSCLC resulting from a synthetic lethal interaction between DDR1 and TMPRSS4

Direct-acting Antivirals for the Treatment of Kidney Transplant Patients With Chronic Hepatitis C Virus Infection in Spain: A Long-term Prospective Observational Study

Background: Direct-acting antivirals (DAA) allow effective and safe eradication of hepatitis C virus (HCV) in most patients. There are limited data on the long-term effects of all-oral, interferon-free DAA combination therapies in kidney transplant (KT) patients infected with HCV. Here we evaluated the long-term tolerability, efficacy, and safety of DAA combination therapies in KT patients with chronic HCV infection. Methods: Clinical data from KT patients treated with DAA were collected before, during, and after the treatment, including viral response, immunosuppression regimens, and kidney and liver function. Results: Patients (N = 226) were mostly male (65.9%) aged 56.1 +/- 10.9 years, with a median time from KT to initiation of DAA therapy of 12.7 years and HCV genotype 1b (64.6%). Most patients were treated with sofosbuvir-based therapies. Rapid virological response at 1 month was achieved by 89.4% of the patients and sustained virological response by week 12 by 98.1%. Liver function improved significantly after DAA treatment. Tacrolimus dosage increased 37% from the beginning of treatment (2.5 +/- 1.7 mg/d) to 1 year after the start of DAA treatment (3.4 +/- 1.9 mg/d, P < 0.001). Median follow-up was 37.0 months (interquartile range, 28.4-41.9) and death-censored graft survival was 91.1%. Adverse events resulting from DAA treatment, especially anemia, were reported for 31.0% of the patients. Conclusions: Chronic HCV infection can be treated efficiently and safely with DAA therapy in KT patients. Most patients retained stable kidney function and improved liver function. Tacrolimus dose had to be increased in most patients, potentially as a result of better liver function

State-of-the-art of spatial arch bridges

The paper describes a new form of bridge called a spatial arch bridge. This bridge type was developed in response to the demand for landmark structures, which have started to appear in the modern urban landscape to provide a symbol of originality, innovation and progress. Spatial arch bridges are defined as bridges in which the vertical deck loads produce bending moments and shear forces not contained in the arch plane, owing to their geometrical and structural configuration. Moreover, the arch itself may not be contained in a plane. The different variables and geometries that create such a structural configuration have been studied and classified. A wide compilation of examples of this bridge type has been made in chronological order, according to their construction date, from Maillarts first concrete spatial arch bridges to the latest designs and materials

Wage inequality, segregation by skill and the price of capital in an assignment model

Some pieces of empirical evidence suggest that in the U.S., over the last few decades, (i) wage inequality between-plants has risen much more than wage inequality within-plants and (ii) there has been an increase in the segregation of workers by skill into separate plants. This paper presents a frictionless assignment model in which these two features can be explained simultaneously as the result of the decline in the relative price of capital. Additional implications of the model regarding the skill premium and the dispersion in labor productivity across plants are also consistent with the empirical evidence. [resumen de autor

Employment generation by small firms in Spain

Despite the relevance in terms of policy, we still know little in Spain about where and by whom jobs are created, and how that is affecting the size distribution of firms. The main innovation of this paper is to use a rich database that overcomes the problems encountered by other firm-level studies to shed some light on the employment generation of small firms in Spain. We find that small firms contribute to employment disproportionately across all sectors of the economy although the difference between their employment and job creation share is largest in the manufacturing sector. The job creators in that sector are both new and established firms whereas only new small firms outperform their larger counterparts in the service sector. The large annual job creation of the small firm size class is shifting the firm size distribution towards the very small production units, although not uniformly across industries of different technology intensit