An efficient approach to noise analysis through multidimensional physics-based models

IEEE TRANS. EL. DEV

Formation of emerging disinfection byproducts in water and evaluation of potential genotoxic effects: the case of chlorinated polycyclic aromatic hydrocarbons

Work performed by Departamento de Genética, Instituto Nacional de Saúde Dr. Ricardo Jorge (INSA); Centro de Química Estrutural, Instituto Superior Técnico, Technical University of Lisbon; Departamento de Saúde Ambiental, INSADisinfection byproducts (DBPs) are formed when disinfectants used in water treatment plants (WTPs) react with natural (or anthropogenic) organic matter present in the source water. Many studies have addressed health risks posed by a life-time exposure to DBPs through chlorinated drinking water or through dermal or inhalation exposure routes. Experimental studies have revealed genotoxic and carcinogenic effects of some DBPs and epidemiological studies evidenced potential associations between chlorinated drinking water and bladder or colorectal cancer. In addition, a possible link between chlorinated drinking water and reproductive/developmental effects has been hypothesized. Many DBPs have been identified in treated water, which justifies the growing concern about the potential health effects of emerging unregulated DBPs, some of which appear to be more genotoxic, in some assays, than the regulated DBPs. Polycyclic aromatic hydrocarbons (PAHs) are among the most persistent contaminants detected in environmental samples such as river sediments and tap water. Water chlorination can lead to the formation of chlorinated derivatives of PAHs (Cl-PAHs) and the few available toxicological studies have shown that Cl-PAHs possess greater mutagenicity than the corresponding parent PAHs. The present study had two main objectives: 1) identification of the major chlorinated derivatives of benzo[a]pyrene (BaP) and fluoranthene (Fluo) formed as chlorination by-products and 2) evaluation of their potential hazard to humans, through the characterization of their potential genotoxic effects in a human cell line. To synthesize chlorinated standards of PAHs, a newly two phase (water/n-hexane) method was developed for BaP and Fluo. 6-Cl-BaP was obtained as the major chlorination product of BaP, and 3-Cl-Fluo and 1,3-Cl2-Fluo of Fluo. The formation of these BaP and Fluo chlorinated derivatives was also observed under WTPs chlorination conditions after at 0.5 until 24 h of exposure. The effects of equimolar concentrations of 6-Cl-BaP vs. BaP and of 3-Cl-Fluo/1,3-Cl2-Fluo vs. Fluo on cell viability and DNA integrity were assessed by the neutral red uptake (NR) and the comet assay, respectively. Exposure of HepG2 cells to a dose-range of 6-Cl-BaP and BaP showed that both compounds are cytotoxic above 50 µM and that, at the equimolar doses of 100 and 125 µM, 6-Cl-BaP is able to induce a significantly higher level of DNA damage than BaP. On the other hand, no changes of cell viability were observed after exposure to several concentrations of Fluo and its derivatives. Likewise, none of the compounds was able to significantly induce DNA damage. In conclusion, the present data confirmed that chlorinated derivatives of BaP and Fluo are formed during WTPs chlorination procedures and allowed the identification of their major chlorinated derivatives that should be further analysed in drinking water. On the other hand, the results from the comet assay evidenced a higher DNA damaging effect of Cl-BaP comparatively to its parent compound, suggestive of a more potent genotoxic effect. In spite of the negative results found for Fluo and its chorinated products, further genotoxicity studies are still needed to allow a definite conclusion. Although health risks of DBPs are small compared to health risks of waterborne diseases, the identification of hazardous Cl-PAHs in water emphasizes the need of development of new and safer water disinfection methods

Gefitinib inhibits the ability of human bone marrow stromal cells to induce osteoclast differentiation: implications for the pathogenesis and treatment of bone metastasis.

Significant relief of bone pain in patients with bone metastases was observed in a clinical trial of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in breast cancer. Osteoclast activation and differentiation are regulated by bone marrow stromal cells (BMSC), a heterogeneous cell compartment that comprehends undifferentiated mesenchymal stem cells (MSC) and their specialized progeny. In this regard, we found that human primary BMSCs express immunoreactive EGFR. Expression of EGFR mRNA and protein was also demonstrated in two human, continuous MSC-like cell lines, HDS-1 and HDS-2 cells. Treatment of HDS cells with EGF produced a significant increase in the levels of activated EGFR which was not observed in the presence of gefitinib. A significant reduction in the basal levels of activation of the EGFR and of Akt was observed in HDS cells following treatment with gefitinib. Treatment of HDS cells with gefitinib produced a significant reduction in the levels of secreted macrophage colony-stimulating factor (M-CSF) and cell-associated receptor activator of NF-kappaB ligand (RANKL) in both cell lines, as assessed by using specific ELISA and Western blotting techniques. Finally, the ability to sustain the differentiation of pre-osteoclasts of conditioned medium from gefitinib-treated HDS cells was reduced by approximately 45% as compared with untreated HDS cells. These data have demonstrated for the first time that the EGFR regulates the ability of BMSCs to induce osteoclast differentiation and strongly support clinical trials of gefitinib in breast cancer patients with bone disease

Peak effect and its evolution with defect structure in YBa2Cu3O7-d thin films at microwave frequencies

The vortex dynamics in YBa2Cu3O7-d thin films have been studied at microwave frequencies. A pronounced peak in the surface resistance, Rs, is observed in these films at frequencies of 4.88 and 9.55 GHz for magnetic fields varying from 0.2 to 0.8 T. The peak is associated with an order-disorder transformation of the flux line lattice as the temperature or field is increased. The occurrence of the peak in Rs is crucially dependent on the depinning frequency, wp and on the nature and concentration of growth defects present in these films. Introduction of artificial defects by swift heavy ion irradiation with 200 MeV Ag ion at a fluence of 4x1010 ions/cm2 enhances wp and suppresses the peak at 4.88 GHz but the peak at 9.55 GHz remains unaffected. A second peak at lower temperature has also been observed at 9.55 GHz. This is related to twin boundaries from angular dependence studies of Rs. Based on the temperature variation of Rs, vortex phase diagrams have been constructed at 9.55 GHz.Comment: 8 pages, 4 figures Submitted to Physical Review

Research of the optical communications groups at University of Aveiro and Institute of Telecommunications - Aveiro Pole

This paper summarizes the research activities of the optical communications group at University of Aveiro and Institute of Telecommunications – Aveiro pole. Several activities like clock recovery systems, both electrical and all optical, electrical equalizers for very high bit rate DST systems, post-detection filters for multigigabit optical receivers, soliton systems, simulation work on WDM, DST, EDFA and short pulse generation for high bit rate systems are presented

Noncommutative quantum mechanics and Bohm's ontological interpretation

We carry out an investigation into the possibility of developing a Bohmian interpretation based on the continuous motion of point particles for noncommutative quantum mechanics. The conditions for such an interpretation to be consistent are determined, and the implications of its adoption for noncommutativity are discussed. A Bohmian analysis of the noncommutative harmonic oscillator is carried out in detail. By studying the particle motion in the oscillator orbits, we show that small-scale physics can have influence at large scales, something similar to the IR-UV mixing

Interacting Kasner-type cosmologies

It is well known that Kasner-type cosmologies provide a useful framework for analyzing the three-dimensional anisotropic expansion because of the simplification of the anisotropic dynamics. In this paper relativistic multi-fluid Kasner-type scenarios are studied. We first consider the general case of a superposition of two ideal cosmic fluids, as well as the particular cases of non-interacting and interacting ones, by introducing a phenomenological coupling function $q(t)$. For two-fluid cosmological scenarios there exist only cosmological scaling solutions, while for three-fluid configurations there exist not only cosmological scaling ones, but also more general solutions. In the case of triply interacting cosmic fluids we can have energy transfer from two fluids to a third one, or energy transfer from one cosmic fluid to the other two. It is shown that by requiring the positivity of energy densities there always is a matter component which violates the dominant energy condition in this kind of anisotropic cosmological scenarios.Comment: Accepted for publication in Astrophysics &Space Science, 8 page

Metabolome-wide association study on ABCA7 indicates a role of ceramide metabolism in Alzheimer’s disease

Genome-wide association studies (GWASs) have identified genetic loci associated with the risk of Alzheimer’s disease (AD), but the molecular mechanisms by which they confer risk are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWASs using untargeted metabolic profiling (metabolomics) by ultraperformance liquid chromatography–mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single-nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0 × 10−5 to 1.3 × 10−44). We showed that plasma LacCer concentrations are associated with cognitive performance and genetically modified levels of LacCer are associated with AD risk. We then showed that concentrations of sphingomyelins, ceramides, and hexosylceramides were altered in brain tissue from Abca7 knockout mice, compared with wild type (WT) (P = 0.049–1.4 × 10−5), but not in a mouse model of amyloidosis. Furthermore, activation of microglia increases intracellular concentrations of hexosylceramides in part through induction in the expression of sphingosine kinase, an enzyme with a high control coefficient for sphingolipid and ceramide synthesis. Our work suggests that the risk for AD arising from functional variations in ABCA7 is mediated at least in part through ceramides. Modulation of their metabolism or downstream signaling may offer new therapeutic opportunities for AD