NUMERICAL EVALUATION OF THE TEMPORAL VARIATION OF VIBRATIONS INDUCED BY UNDERGROUND TRAINS

The change in the dynamic response of shallow soils as caught by two geophysical test campaigns is exploited to numerically predict the variation in the ground borne vibrations induced by the passage of underground trains. Multiple causes may lead to a variation in the perception of vibrations over time: from an increase in the train load to the roughness of the railway track, from the increase of the train speed to the modification of the dynamic response of the surrounding soil. In the present study, special attention is devoted to the effect of the hydrological regime on the latter. Two scenarios were calibrated on the results of repeated geodynamic tests on the same site in Milano but at two different times. The two investigations revealed differences in the dynamic response of above-ground soils which can be related to different saturation profiles. The passage of a typical convoy is simulated in the time domain. Differences between the two scenarios are highlighted together with the role played by the static axle load of the train. Furthermore, comparisons with recorded accelerations are provided to validate the model

A numerical assessment of variable saturation of the upper layers on the ground borne vibrations from underground trains: A case history

Ground borne vibrations generated by the passage of underground trains may change over time due to objective causes, such as increasing weight and speed of trains or ageing of the infrastructure components, as well as a variation in the dynamic response of the soil surrounding the tunnel. Among the possible causes of changes in the soil dynamic response, its hydrologic state has been seldom investigated. In this contribution, the role played by the conditions of the soil above the water table is addressed, starting from a case history in the city of Milano. Two-dimensional plane strain numerical models have been developed for the infrastructure. The models were calibrated on the results of two geophysical investigations performed at the same site in the city centre, but at two different times, which allowed distinguishing different dynamic responses. The system was excited by a synthetic load time history, matching a reference dynamic load spectrum included in Italian recommendations. Limitations of using this input on a 2D plane strain model were assessed by comparing the computed vibrations with experimental acceleration records collected on the tunnel. The results of the two numerical models are compared with those of a simulation performed assuming fully dry conditions above the water table. Overall, the set of analyses shows that even small changes in the dynamic response of the soil, interpretated as a consequence of variable saturation, may result in a change of a few decibels in the acceleration levels. Much larger accelerations are predicted on average with the simpler dry model, clearly showing the advantages of a more accurate modelling strategy

RNASET2 as a tumor antagonizing gene in a melanoma cancer model

The RNASET2 gene, mapped in 6q27, was previously found to exert control of tumorigenesis in an ovarian cancer system. We present here results indicating a similar control in a melanoma cancer model. Thus, this gene is most likely involved in a common general pathway of tumorigenesis. Moreover, its antitumorigenic activity is manifested in vivo but not in vitro, suggesting that this gene belongs to the growing category of tumor antagonizing/malignancy suppressor genes. A possible role of RNASET2 in the activation of a senescence program, whose responsible locus was mapped in the same chromosomal 6q27 region, seems to be inconsistent with our data

Human RNASET2: A Highly Pleiotropic and Evolutionary Conserved Tumor Suppressor Gene Involved in the Control of Ovarian Cancer Pathogenesis

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strat- egy and as such, is expected to provide in the incoming years significant benefits for ovarian cancer treatment as well. Here, we provide a detailed survey on the highly pleiotropic oncosuppressive roles played by the human RNASET2 gene, whose protein product has been consistently reported to estab- lish a functional crosstalk between ovarian cancer cells and key cellular effectors of the innate immune system (the monocyte/macrophages lineage), which is in turn able to promote the recruitment to the cancer tissue of M1-polarized, antitumoral macrophages. This feature, coupled with the ability of T2 ribonucleases to negatively affect several cancer-related parameters in a cell-autonomous manner on a wide range of ovarian cancer experimental models, makes human RNASET2 a very promising candidate to develop a “multitasking” therapeutic approach for innovative future applications for ovarian cancer treatment

The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae

The cellular response to stress conditions involves a decision between survival or cell death when damage is severe. A conserved stress response in eukaryotes involves endonucleolytic cleavage of transfer RNAs (tRNAs). The mechanism and significance of such tRNA cleavage is unknown. We show that in yeast, tRNAs are cleaved by the RNase T2 family member Rny1p, which is released from the vacuole into the cytosol during oxidative stress. Rny1p modulates yeast cell survival during oxidative stress independently of its catalytic ability. This suggests that upon release to the cytosol, Rny1p promotes cell death by direct interactions with downstream components. Thus, detection of Rny1p, and possibly its orthologues, in the cytosol may be a conserved mechanism for assessing cellular damage and determining cell survival, analogous to the role of cytochrome c as a marker for mitochondrial damage

OTX genes in adult tissues

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the “toolbox” to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets

Sexual dysfunction and fertility-related distress in young adults with cancer over 5 years following diagnosis: study protocol of the Fex-Can Cohort study

BACKGROUND: There is a lack of firm knowledge regarding sexual problems and fertility-related distress in young adults following a diagnosis with cancer. Establishing such understanding is essential to identify patients in need of specific support and to develop cancer care accordingly. This study protocol describes the Fex-Can Cohort study, a population-based prospective cohort study investigating sexual dysfunction and fertility-related distress in young adults diagnosed with cancer in Sweden. The primary objective of the study is to determine the prevalence and predictors of sexual dysfunction and fertility-related distress following a cancer diagnosis in young adulthood compared to prevalence rates for the general population. Further aims are to investigate the trajectories of these issues over time, the co-existence between sexual dysfunction and fertility-related distress, and the relation between these issues and body image, anxiety and depression, health-related quality of life, self-efficacy related to sexuality and fertility, and fertility-related knowledge. METHODS: Participants in the Fex-Can Cohort will be identified via the Swedish National Quality Registries for Brain Tumors, Breast Cancer, Gynecological Oncology, Lymphoma, and Testicular Cancer. All patients diagnosed at the ages of 18-39, during a period of 18 months, will be invited to participate. Established instruments will be used to measure sexual function (PROMIS SexFS), fertility-related distress (RCAC), body image (BIS), anxiety and depression (HADS), and health-related quality of life (QLQ-C30); Self-efficacy and fertility-related knowledge will be assessed by study-specific measures. The survey will be administered to participants at baseline (approximately 1.5 year after diagnosis) and at 3 and 5 years post-diagnosis. Registry data will be used to collect clinical variables. A comparison group of 2000 young adults will be drawn from the Swedish population register (SPAR) and subsequently approached with the same measures as the cancer group. DISCUSSION: The study will determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young men and women with cancer. The findings will form a basis for developing interventions to alleviate sexual problems and fertility-related distress in young adults with cancer in the short and long term. TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was therefore not obtained