The Virgo interferometric gravitational antenna

Submitted to: Class. Quantum Grav.The interferometric gravitational wave detectors represent the ultimate evolution of the classical Michelson interferometer. In order to measure the signal produced by the passage of a gravitational wave, they aim to reach unprecedent sensitivities in measuring the relative displacements of the mirrors. One of them , the 3-km-long Virgo gravitational wave antenna, which will be particularly sensitive in the low frequency range (10-100 Hz), is presently in its commissioning phase. In this paper the various techniques developed in order to reach its target extreme performance are outlined

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

STRUCTURAL AND FUNCTIONAL-ASPECTS OF CALCIUM HOMEOSTASIS IN EUKARYOTIC CELLS

The maintenance of a low cytosolic free-Ca2+ concentration, ([Ca2+]i) is a common feature of all eukaryotic cells. For this purpose a variety of mechanisms have developed during evolution to ensure the buffering of Ca2+ in the cytoplasm, its extrusion from the cell and/or its accumulation within organelles. Opening of plasma membrane channels or release of Ca2+ from intracellular pools leads to elevation of [Ca2+]i; as a result, Ca2+ binds to cytosolic proteins which translate the changes in [Ca2+]i into activation of a number of key cellular functions. The purpose of this review is to provide a comprehensive description of the structural and functional characteristics of the various components of [Ca2+]i homeostasis in eukaryotes

Responses of mouse lymphocytes to extracellular ATP. II Extracellular ATP causes cell type-dependent lysis and DNA fragmentation

Extracellular ATP (ATPo) caused dose-dependent lysis of YAC-1 and P-815 mouse tumor cells. This event, assessed by 51Cr release, was accompanied by sustained depolarization of the plasma membrane potential and Ca2+ influx. Plasma membrane depolarization and Ca2+ influx occurred within a few seconds of ATPo addition to both cell types, whereas 51Cr was released without apparent lag in YAC-1 cells and after 2 h in P-815 cells. Furthermore, a rise in [Ca2+]i was required for ATPo-dependent lysis of YAC-1 but not P-815 cells. In P-815 cells, ATPo caused an early and [Ca2+]i-independent DNA fragmentation that occurred at lower nucleotide concentrations than those required to trigger 51Cr release. Instead in YAC-1 cells very low concentrations of ATPo caused early lysis (ED50 for lysis about 200 microM) accompanied by only barely detectable DNA fragmentation. Previous studies disclosed that lymphokine-activated killer cells are fully resistant to the membrane-perturbing effects of ATPo. We show that lymphokine-activated killer cells also do not undergo DNA fragmentation even in the presence of high ATPo concentrations. This study complements previous observations on the lytic effects of ATPo and shows that this nucleotide can also cause DNA fragmentation, one of the earliest target cell alterations observed during CTL-mediated lysis

Role of the purinergic P2Z receptor in spontaneous cell death in J774 macrophage cultures

J774 mouse macrophages express an ionotropic receptor gated by extracellular ATP. Activation of this receptor, currently named purinergic P2Z, causes transmembrane ion fluxes, plasma membrane depolarization, cell swelling and eventual cell death. The physiological role of this receptor is as yet unknown. In the present report we show that macrophage cell clones that hypo-express the P2Z receptor showed a very low degree of spontaneous cell death in culture, while hyper-expressing clones were exceedingly susceptible to cell death. To further support a role for ATP receptors in spontaneous cell death, addition to the macrophage cell cultures of oxidized ATP, a selective inhibitor of ionotropic purinergic receptors, or the ATP-hydrolysing enzyme apyrase, also reduced spontaneous death

Synergistic effect of extracellular adenosine 5-triphosphate and tumor necrosis factor on DNA degradation

Extracellular ATP (ATPo) was recently considered a possible mediator of cell-mediated cytotoxicity since it is secreted by effector cells following appropriate stimulus and causes lysis as well as DNA degradation of susceptible target cells. This hypothesis however is not readily reconciled with the finding that ATPo-resistant cells are fully susceptible to intact effector cells, which instead suggests that a necessary step in cell-mediated cytotoxicity is the interaction between different molecules released by a cytotoxic cell. By combining ATPo with TNF or lymphotoxin (LT), cytokines which induce late DNA damage, we observed a synergistic effect on target cell death. Under these conditions, the phenomenon of DNA degradation also appeared early, with a kinetics reminiscent of that observed during target cell incubation with intact effector cells. Target cells which are resistant to one of the two molecules exhibited an enhanced rate of cell death when exposed to their association. Target cell lysis and DNA degradation were also Ca(2+)-independent events as they took place following external Ca2+ chelation by EGTA addition and under experimental conditions in which little or no Ca2+ was released from target cell intracellular stores. These findings suggest that ATPo might represent a further mediator which is responsible for the alternative Ca(2+)-independent cytolytic pathway in association with other molecules released by effector cytotoxic lymphocytes