Regulation of NKG2D-Dependent NK Cell Functions: The Yin and the Yang of Receptor Endocytosis.

Natural-killer receptor group 2, member D (NKG2D) is a well characterized natural killer (NK) cell activating receptor that recognizes several ligands poorly expressed on healthy cells but up-regulated upon stressing stimuli in the context of cancer or viral infection. Although NKG2D ligands represent danger signals that render target cells more susceptible to NK cell lysis, accumulating evidence demonstrates that persistent exposure to ligand-expressing cells causes the decrease of NKG2D surface expression leading to a functional impairment of NKG2D-dependent NK cell functions. Upon ligand binding, NKG2D is internalized from the plasma membrane and sorted to lysosomes for degradation. However, receptor endocytosis is not only a mechanism of receptor clearance from the cell surface, but is also required for the proper activation of signalling events leading to the functional program of NK cells. This review is aimed at providing a summary of current literature relevant to the molecular mechanisms leading to NKG2D down-modulation with particular emphasis given to the role of NKG2D endocytosis in both receptor degradation and signal propagation. Examples of chronic ligand-induced down-regulation of NK cell activating receptors other than NKG2D, including natural cytotoxicity receptors (NCRs), DNAX accessory molecule-1 (DNAM1) and CD16, will be also discussed

Advanced radar absorbing ceramic-based materials for multifunctional applications in space environment

In this review, some results of the experimental activity carried out by the authors on advanced composite materials for space applications are reported. Composites are widely employed in the aerospace industry thanks to their lightweight and advanced thermo-mechanical and electrical properties. A critical issue to tackle using engineered materials for space activities is providing two or more specific functionalities by means of single items/components. In this scenario, carbon-based composites are believed to be ideal candidates for the forthcoming development of aerospace research and space missions, since a widespread variety of multi-functional structures are allowed by employing these materials. The research results described here suggest that hybrid ceramic/polymeric structures could be employed as spacecraft-specific subsystems in order to ensure extreme temperature withstanding and electromagnetic shielding behavior simultaneously. The morphological and thermo-mechanical analysis of carbon/carbon (C/C) three-dimensional (3D) shell prototypes is reported; then, the microwave characterization of multilayered carbon-filled micro-/nano-composite panels is described. Finally, the possibility of combining the C/C bulk with a carbon-reinforced skin in a synergic arrangement is discussed, with the aid of numerical and experimental analyses

Emotion and Knowledge in Decision Making under Uncertainty

This paper presents four incentivised experiments analysing jointly the separate role of immediate integral emotions and knowledge in individual decision making under ambiguity. Reactions to a natural source of uncertainty (i.e., forthcoming real-world election results) were measured using both computed decision weights derived from individual choices and judgmental probabilities determined from the subjects\u2019 estimated likelihood of election outcomes. This study used self-reports to measure emotions aroused by the prospective election victory of a party/coalition of parties, and both self-assessed and actual competence to measure knowledge of politics. This paper found evidence of both preference for ambiguity in the gain domain and of likelihood insensitivity, namely the tendency to overweight unlikely events and to underweight likely events. This paper also shows that a superior knowledge of politics was associated with a preference for ambiguity (i.e., the elevation of the decision weighting function for gains). Both stronger positive emotions and superior knowledge generally have asymmetric eects on likelihood insensitivity (i.e., the curvature of the decision weighting function), each being associated separately with higher overweighting of unlikely election outcomes

A new advanced railgun system for debris impact study

The growing quantity of debris in Earth orbit poses a danger to users of the orbital environment, such as spacecraft. It also increases the risk that humans or manmade structures could be impacted when objects reenter Earth's atmosphere. During the design of a spacecraft, a requirement may be specified for the surviv-ability of the spacecraft against Meteoroid / Orbital Debris (M/OD) impacts throughout the mission; further-more, the structure of a spacecraft is designed to insure its integrity during the launch and, if it is reusable, during descent, re-entry and landing. In addition, the structure has to provide required stiffness in order to allow for exact positioning of experiments and antennas, and it has to protect the payload against the space environment. In order to decrease the probability of spacecraft failure caused by M/OD, space maneuver is needed to avoid M/OD if the M/OD has dimensions larger than 10cm, but for M/OD with dimensions less than 1cm M/OD shields are needed for spacecrafts. It is therefore necessary to determine the impact-related failure mechanisms and associated ballistic limit equations (BLEs) for typical spacecraft components and subsys-tems. The methods that are used to obtain the ballistic limit equations are numerical simulations and la-borato-ry experiments. In order to perform an high energy ballistic characterization of layered structures, a new ad-vanced electromagnetic accelerator, called railgun, has been assembled and tuned. A railgun is an electrically powered electromagnetic projectile launcher. Such device is made up of a pair of parallel conducting rails, which a sliding metallic armature is accelerated along by the electromagnetic effect (Lorentz force) of a cur-rent that flows down one rail, into the armature and then back along the other rail, thanks to a high power pulse given by a bank of capacitors. A tunable power supplier is used to set the capacitors charging voltage at the desired level: in this way the Rail Gun energy can be tuned as a function of the desired bullet velocity. This facility is able to analyze both low and high velocity impacts. A numerical simulation is also performed by using the Ansys Autodyn code in order to analyze the damage. The experimental results and numerical simulations show that the railgun-device is a good candidate to perform impact testing of materials in the space debris energy range

Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic sphingomyelinase.

Intracellular pathways leading from membrane receptor engagement to apoptotic cell death are still poorly characterized. We investigated the intracellular signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly expressed cell surface receptor whose engagement results in triggering of cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody was produced by immunizing mice with human CD95-transfected L cells. Crosslinking of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95-transfected murine cells, as demonstrated by induction of in vivo sphingomyelin (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM vesicles as substrates, showed strong SMase activity, which required pH 5.0 for optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C2-ceramide. These data indicate that CD95 cross-linking induces SM breakdown and ceramide production through an acidic SMase, thus providing the first information regarding early signal generation from CD95, and may be relevant in defining the biochemical nature of intracellular messengers leading to apoptotic cell death

Noise control in hospitals: Considerations on regulations, design and real situations

Hospitals include a variety of different spaces with different requirements and levels of sensitivity but also different activities and equipment that can cause high noise levels. Despite the regulations that usually apply to hospitals, noise control is not an easy task. In Italy, the design and construction of hospital buildings must guarantee the acoustic requirements given by the National Regulation (1995-1997), which refers to all new buildings, and by the new Decree on Minimum Environmental Criteria (2017), which applies to public buildings and refers to the Italian acoustic classification scheme (UNI 11367-2010). However, the need to create spaces suitable for the various types of use entails difficulties in identifying where and how to apply the limits set by the legislation. In addition, there are situations in which, regardless of the legislation, it would be opportune to consider more adequate acoustic comfort. In the paper, we analyse the various situations and evaluate the applicability of the legislation. From experimental measurements performed in real cases, some methodological proposals are reported both to ensure the satisfaction of the requirements imposed by the legislation and to meet the needs for more specific acoustic regulations for hospital