The effects of a Variable IMF on the Chemical Evolution of the Galaxy

In this work we explore the effects of adopting an initial mass function (IMF) variable in time on the chemical evolution of the Galaxy. In order to do that we adopt a chemical evolution model which assumes two main infall episodes for the formation of the Galaxy. We study the effects on such a model of different IMFs. First, we use a theoretical one based on the statistical description of the density field arising from random motions in the gas. This IMF is a function of time as it depends on physical conditions of the site of star formation. We also investigate the behaviour of the model predictions using other variable IMFs, parameterized as a function of metallicity. Our results show that the theoretical IMF when applied to our model depends on time but such time variation is important only in the early phases of the Galactic evolution, when the IMF is biased towards massive stars. We also show that the use of an IMF which is a stronger function of time does not lead to a good agreement with the observational constraints suggesting that if the IMF varied this variation should have been small. Our main conclusion is that the G-dwarf metallicity distribution is best explained by infall with a large timescale and a constant IMF, since it is possible to find variable IMFs of the kind studied here, reproducing the G-dwarf metallicity but this worsens the agreement with other observational constraints.Comment: 7 pages, to appear in "The Chemical Evolution of the Milky Way: Stars vs Clusters", Vulcano, September 1999, F. Giovannelli and F. Matteucci eds. (Kluwer, Dordrecht) in pres

The antimetastatic and antiangiogenesis effects of kefir water on murine breast cancer cells

Background. Kefir is a unique cultured product that contains beneficial probiotics. Kefir culture from other parts of the world exhibits numerous beneficial qualities such as anti-inflammatory, immunomodulation, and anticancer effects. Nevertheless, kefir cultures from different parts of the world exert different effects because of variation in culture conditions and media. Breast cancer is the leading cancer in women, and metastasis is the major cause of death associated with breast cancer. The antimetastatic and antiangiogenic effects of kefir water made from kefir grains cultured in Malaysia were studied in 4T1 breast cancer cells. Methods. 4T1 cancer cells were treated with kefir water in vitro to assess its antimigration and anti-invasion effects. BALB/c mice were injected with 4T1 cancer cells and treated orally with kefir water for 28 days. Results. Kefir water was cytotoxic toward 4T1 cells at IC50 (half-maximal inhibitory concentration) of 12.5 and 8.33 mg/mL for 48 and 72 hours, respectively. A significant reduction in tumor size and weight (0.9132 ± 0.219 g) and a substantial increase in helper T cells (5-fold) and cytotoxic T cells (7-fold) were observed in the kefir water–treated group. Proinflammatory and proangiogenic markers were significantly reduced in the kefir water–treated group. Conclusions. Kefir water inhibited tumor proliferation in vitro and in vivo mainly through cancer cell apoptosis, immunomodulation by stimulating T helper cells and cytotoxic T cells, and anti-inflammatory, antimetastatic, and antiangiogenesis effects. This study brought out the potential of the probiotic beverage kefir water in cancer treatment

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe