Functional Inactivation of Drosophila GCK Orthologs Causes Genomic Instability and Oxidative Stress in a Fly Model of MODY-2

Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.     

Modelling direct sequence pseudonoise(dspn) satellite reception with directional antennas in the dense scatterer mobile environment

A geometric propagation model is developed for simulating the reception of direct sequence pseudonoise (DSPN) satellite signals by a directional or omni antenna in the dense scatterer mobile environment. The model is first validated for narrowband signals by a direct comparison of both simulated cumulative signal strength statistics and simulated diffuse Doppler spectra with classical theory. The model is then used to predict fading statistics for DSPN signaling, either with omni or directional antennas. As expected, the mitigation of fading is closely related to the ratio of DSPN chip duration to delay spread of the scatterer medium for both the omni and directional antennas.     

MMP1 and MMP11 Expression in Peripheral Blood Mononuclear Cells upon Their Interaction with Breast Cancer Cells and Fibroblasts

Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior.     

The Landscape of microRNAs in βCell: Between Phenotype Maintenance and Protection

Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.     

A survey of support for structured communication in concurrency control models

The two standard models used for communication in concurrent programs, shared memory and message passing, have been the focus of much debate for a long time. Still, we believe the main issue at stake should not be the choice between these models, but rather how to ensure that communication is structured, i.e., it occurs only in syntactically restricted code regions. In this survey, we explore concurrency control models and evaluate how their characteristics contribute positively or negatively to the support for structured communication. We focus the evaluation on three properties: reasonability, which is the main property we are interested in and determines how easily programmers can reason about a concurrent program’s execution; performance, which determines whether there are any distinct features which can prevent or facilitate efficient implementations; and composability, which determines whether a model offers constructs that can be used as building blocks for coarser-grained, or higher-level, concurrency abstractions.     

Utilization of Ultrasonic Measurements for Determining the Variations in Microstructure of Thermally Degraded 2205 Duplex Stainless Steel

The aim of this study is to investigate the changes in attenuation of longitudinal waves and velocity of shear wave modes for assessing variations in the microstructure of thermally degraded 2205 duplex stainless steel samples that were aged isothermally at 700°C and 900°C for different time intervals. The evaluation of material microstructural changes such as phase transformation and second phase precipitation which are related to material properties is of primary importance to ensure quality of components. This paper presents evidence that indicate that the attenuation coefficient of the longitudinal mode is sensitive to gradual microstructural changes produced by the aging treatments. The gradual changes in microstructure are associated with reduction of impact properties. On the other hand, for samples aged at 700°C, the velocity of the fast mode of shear wave show changes at high aging times and does not show changes at early aging times were the materials properties are already degraded.     

Geodesign application for bio-swale design: rule-based approach stormwater management for Ottawa Street North in Hamilton,Ontario

With increases in storm frequency and intensity, municipalities are finding new ways of managing stormwater. Solutions require collaboration across planning disciplines and input from an informed public. This study compares a system of bioswales to existing curb and gutter infrastructure in a post-industrial streetscape of Hamilton, Ontario. Using the geodesign process, a section of Ottawa St. North was modelled to show how green infrastructure can ease the burden on aging, combined sewer systems. Qualitative data was gathered from residents of the neighbourhood through field notes, and quantitative geospatial data through GIS. Parametric modelling was used to generate a design, and scenarios created to show resulting impacts on stormwater run-off. The model was posted online as an interactive presentation, accessible to all stakeholders for review and comment. The results of the study demonstrate powerful new tools that can assist landscape architects in designing, collaborating and communicating stormwater strategies.     

Characterization of soil deformation due to blast-induced liquefaction by UAV-based photogrammetry and terrestrial laser scanning

ABSTRACT

Soil liquefaction due to an earthquake can lead to permanent soil deformation and reduction of load-bearing capacity that in turn could act on building stability. Since a quantitative evaluation of post-liquefaction settlements is often very difficult, field scale liquefaction tests, carried out under controlled conditions, such as blast tests, are used to perform a correct quantitative analysis of the liquefaction phenomena. Among the significant parameters related to a blast test, there are the geometric ones, i.e. the extension of the area affected by the blast-induced liquefaction and the corresponding vertical displacements. This article shows the results of a blast test carried out at a trial site located in Mirabello (Ferrara, Italy) from a remote-sensing perspective. Data provided by aerial Structure-from-Motion photogrammetry, supported by terrestrial laser scanning measurements, were used to evaluate the soil deformation that, in the specific case study, aided a geological/geotechnical interpretation of the blast test results. In general, the proposed method can be used to characterize areas affected by blast-induced liquefaction, including those cases where blasting is used as ground improvement technique aimed at mitigating the seismic hazard.