Probing the evolution of the near-IR luminosity function of galaxies to z ~ 3 in the Hubble Deep Field South

[Abridged] We present the rest-frame Js-band and Ks-band luminosity function of a sample of about 300 galaxies selected in the HDF-S at Ks<23 (Vega). We use calibrated photometric redshift together with spectroscopic redshift for 25% of the sample. The sample has allowed to probe the evolution of the LF in the three redshift bins [0;0.8), [0.8;1.9) and [1.9;4) centered at the median redshift z_m ~ [0.6,1.2,3]. The values of alpha we estimate are consistent with the local value and do not show any trend with redshift. We do not see evidence of evolution from z=0 to z_m ~ 0.6 suggesting that the population of local bright galaxies was already formed at z<0.8. On the contrary, we clearly detect an evolution of the LF to z_m ~ 1.2 characterized by a brightening of M* and by a decline of phi*. To z_m ~ 1.2 M* brightens by about 0.4-0.6 mag and phi* decreases by a factor 2-3. This trend persists, even if at a less extent, down to z_m ~ 3 both in the Js-band and in the Ks-band LF. The decline of the number density of bright galaxies seen at z>0.8 suggests that a significant fraction of them increases their stellar mass at 1<z<2-3 and that they underwent a strong evolution in this redshift range. On the other hand, this implies also that a significant fraction of local bright/massive galaxies was already in place at z>3. Thus, our results suggest that the assembly of high-mass galaxies is spread over a large redshift range and that the increase of their stellar mass has been very efficient also at very high redshift at least for a fraction of them.Comment: 18 pages, 21 figures, Accepted for publication in MNRA

Induced-Coagulated Plasma-Fibrin Gels as a Biological Scaffold for Cell Attachment and Proliferation of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC)

Fibrin gels are an ideal natural biological scaffold for tissue engineering because they are biocompatible,biodegradable, and have many biological surface markers. However, most research on fi brin gels used commercialfi brin kits that could be costly and limited in some areas. In this study, fi brin gels were made by inducing bloodcoagulation by adding a common diagnostic kit to assess the time for blood to clot, called activated partialthromboplastin time (aPTT). This induced coagulated plasma (iCoplas)-fi brin gels was evaluated for its ability toenhance biological activity of umbilical cord-derived mesenchymal stem cell (UC-MSC), which were cell attachmentand proliferation. Fibrinogen concentration had infl uence on cell attachment, where only 50% of the cells couldattach to 77 mg/dl fi brinogen gels whereas 93% cells adhered to 154 mg/dl fi brin gels. There were no signifi cantdifferences in cell proliferation on polysterene culture dish and fi brin gels (p>0.05). These results showed thatiCoplas-fi brin gels could be used as a fi brin-based scaffold, yielding no signifi cant difference than polysterene-tissueculture dish cultures in cell attachment and cell proliferation on 154 mg/dl fi brinogen concentration

MGMT promoter methylation in plasma of glioma patients receiving temozolomide.

Promoter methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene plays a role in cellular response to alkylating agents. In the present study aimed to: (i) evaluate the concordance between MGMT promoter methylation status in tumor tissue and plasma; (ii) monitor MGMT promoter methylation status in plasma taken before and during temozolomide treatment; (iii) explore the value of MGMT promoter methylation status in plasma as a prognostic/predictive biomarker in glioma patients. We enrolled 58 patients with histologically confirmed glioma at different grades of malignancy. All patients underwent surgical resection and temozolomide treatment. Paraffin-embedded tumor tissue was available for 48 patients. Blood samples were collected from all patients before temozolomide treatment (baseline) and at each MRI examination for a 12-month period. MGMT promoter methylation status was assessed in both sample types by real time PCR with a specific probe. The frequency of MGMT promoter methylation was 60.4 % in tumor tissue and 41.38 % in plasma. MGMT promoter methylation status was concordant in the two sample types (Kappa = 0.75, 95 % confidence interval (CI) 0.57-0.93; p value <0.001). Overall and progression-free survival were longer in patients with methylated MGMT promoter. Mortality was higher in patients with unmethylated MGMT promoter, whether in tumor tissue [hazard ratio (HR) 2.21; 95 % CI 0.99-4.95] or plasma (HR 2.19; 95 % CI 1.02-4.68). Progression-free survival was shorter in patients with unmethylated MGMT promoter, whether in tissue (HR 2.30; 95 % CI 1.19-4.45) or plasma (HR 1.77; 95 % CI 0.95-3.30). The cumulative incidence of unmethylated MGMT promoter in plasma at baseline was 58 %, and reached virtually 100 % at 12 months. In conclusion MGMT promoter methylation status in tumor tissue and plasma was highly concordant, and both were associated with longer survival, supporting the role of the detection of methylated MGMT promoter in predicting treatment response. However we suggest caution in using plasma as a surrogate of tumor tissue due to possible false-negative results

Microfoundations of Strategic Agility in Emerging Markets: Empirical Evidence of Italian MNEs in India

We propose the individual-level microfoundations of subsidiary CEOs in emerging markets as antecedents of the strategic agility of multinational enterprises, and subsidiary embeddedness as a key organizational-level moderator of these relationships. Combining quantitative data on subsidiary CEOs operating in India with qualitative interviews with Italian HQ counterparts, our results suggest that subsidiary CEOs’ tenure in emerging markets, along with their overall experience, affects MNE strategic agility positively. Similarly, CEOs’ cognitive characteristics - problem solving and reasoning, and language and communication skills (individual-level microfoundations) - affected strategic agility positively, while subsidiary embeddedness moderated these relationships in different ways, leaving space for fresh managerial and theoretical considerations. © 2021

Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis

BACKGROUND: The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. METHODS: A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. RESULTS: HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). CONCLUSIONS: This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions

Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort

Introduction: Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research. Methods: The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study’s prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks. Results: The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage. Discussion: This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa