Design and mechanical characterization of voronoi structures manufactured by indirect additive manufacturing

Additive manufacturing (AM) is a production process for the fabrication of three-dimensional items characterized by complex geometries. Several technologies employ a localized melting of metal dust through the application of focused energy sources, such as lasers or electron beams, on a powder bed. Despite the high potential of AM, numerous burdens afflict this production technology; for example, the few materials available, thermal stress due to the focused thermal source, low surface finishing, anisotropic properties, and the high cost of raw materials and the manufacturing process. In this paper, the combination by AM of meltable resins with metal casting for an indirect additive manufacturing (I-AM) is proposed. The process is applied to the production of open cells metal foams, similar in shape to the products available in commerce. However, their cellular structure features were designed and optimized by graphical editor Grasshopper®. The metal foams produced by AM were cast with a lost wax process and compared with commercial metal foams by means of compression tests

Exploring the use of dimethyl fumarate as microglia modulator for neurodegenerative diseases treatment

The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression

Probing the statistical decay and alpha-clustering effects in 12c+12c and 14n+10b reactions

An experimental campaign has been undertaken at INFN Laboratori Nazionali di Legnaro, Italy, in order to progress in our understanding of the statistical properties of light nuclei at excitation energies above particle emission threshold, by measuring exclusive data from fusion-evaporation reactions. A first reaction 12C+12C at 7.9 AMeV beam energy has been measured, using the GARFIELD+Ring Counter experimental setup. Fusion-evaporation events have been exclusively selected. The comparison to a dedicated Hauser-Feshbach calculation allows us to give constraints on the nuclear level density at high excitation energy for light systems ranging from C up to Mg. Out-of-equilibrium emission has been evidenced and attributed both to entrance channel effects favoured by the cluster nature of reaction partners and, in more dissipative events, to the persistence of cluster correlations well above the 24Mg threshold for 6 alphas decay. The 24Mg compound nucleus has been studied with a new measurement 14N + 10B at 5.7 AMeV. The comparison between the two datasets would allow us to further constrain the level density of light nuclei. Deviations from a statistical behaviour can be analyzed to get information on nuclear clustering.Comment: 4 pages, 2 figures, Contribution to conference proceedings of the 25th International Nuclear Physics Conference (INPC 2013

HIV-exposed uninfected children. A systematic review on psychological well-being and association with school performances in Africa

There is a growing number of children affected by HIV in Africa. Research on HIV-exposed uninfected children (HEU) is also growing. This systematic review focuses on the psychological well-being of HEU and its association with school intervention, outcomes, and enrollment in the African context, which is where the rate of HIV reaches its highest levels. Research on public databases was conducted according to PRISMA standards. Only studies on HEU primary school children in Africa, both quantitative and qualitative, were included. Out of 1510 papers retrieved, 50 met the inclusion criteria. These studies demonstrate that HEU children are more likely to perform worse in school compared to their counterparts who were not exposed to HIV and to show poorer concentration in the classroom. Children with parents suffering from AIDS are worried for them and have to take household responsibility, resulting in school dropouts, juvenile work, and risky behaviors. Few interventions have been conducted in the school environment with some of them being successful; therefore, future research should involve schools to create an inclusive environment where HEU children could enhance their potential and improve their psychological health

GARFIELD + RCo Digital Upgrade: a Modern Set-up for Mass and Charge Identification of Heavy Ion Reaction Products

An upgraded GARFIELD + Ring Counter (RCo) apparatus is presented with improved performances as far as electronics and detectors are concerned. On one side fast sampling digital read out has been extended to all detectors, allowing for an important simplification of the signal processing chain together with an enriched extracted information. On the other side a relevant improvement has been made in the forward part of the setup (RCo): an increased granularity of the CsI(Tl) crystals and a higher homogeneity in the silicon detector resistivity. The renewed performances of the GARFIELD + RCo array make it suitable for nuclear reaction measurements both with stable and with Radioactive Ion Beams (RIB), like the ones foreseen for the SPES facility, where the Physics of Isospin can be studied.Comment: 13 pages, 19 figures - paper submitted to Eur. Phys. J.

Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy- relevant energies down to stopping

Track structures and resulting DNA damage in human cells have been simulated for hydrogen, helium, carbon, nitrogen, oxygen and neon ions with 0.25–256 MeV/u energy. The needed ion interaction cross sections have been scaled from those of hydrogen; Barkas scaling formula has been refined, extending its applicability down to about 10 keV/u, and validated against established stopping power data. Linear energy transfer (LET) has been scored from energy deposits in a cell nucleus; for very low-energy ions, it has been defined locally within thin slabs. The simulations show that protons and helium ions induce more DNA damage than heavier ions do at the same LET. With increasing LET, less DNA strand breaks are formed per unit dose, but due to their clustering the yields of double-strand breaks (DSB) increase, up to saturation around 300 keV/μm. Also individual DSB tend to cluster; DSB clusters peak around 500 keV/μm, while DSB multiplicities per cluster steadily increase with LET. Remarkably similar to patterns known from cell survival studies, LET-dependencies with pronounced maxima around 100– 200 keV/μm occur on nanometre scale for sites that contain one or more DSB, and on micrometre scale for megabasepair-sized DNA fragments

A novel strategy for molecular interfaces optimization: the case of ferritin-transferrin receptor interaction

Protein-protein interactions regulate almost all cellular functions and rely on a fine tune of surface amino acids properties involved on both molecular partners. The disruption of a molecular association can be caused even by a single residue mutation, often leading to a pathological modification of a biochemical pathway. Therefore the evaluation of the effects of amino acid substitutions on binding, and the ad hoc design of protein-protein interfaces, is one of the biggest challenges in computational biology. Here, we present a novel strategy for computational mutation and optimization of protein-protein interfaces. Modeling the interaction surface properties using the Zernike polynomials, we describe the shape and electrostatics of binding sites with an ordered set of descriptors, making possible the evaluation of complementarity between interacting surfaces. With a Monte Carlo approach, we obtain protein mutants with controlled molecular complementarities. Applying this strategy to the relevant case of the interaction between Ferritin and Transferrin Receptor, we obtain a set of Ferritin mutants with increased or decreased complementarity. The extensive molecular dynamics validation of the method results confirms its efficacy, showing that this strategy represents a very promising approach in designing correct molecular interfaces

Negative parental responses to coming out and family functioning in a sample of lesbian and gay young adults

Parental responses to youths' coming out (CO) are crucial to the subsequent adjustment of children and family. The present study investigated the negative parental reaction to the disclosure of same-sex attraction and the differences between maternal and paternal responses, as reported by their homosexual daughters and sons. Participants' perceptions of their parents' reactions (evaluated through the Perceived Parental Reactions Scale, PPRS), age at coming out, gender, parental political orientation, and religiosity involvement, the family functioning (assessed through the Family Adaptability and Cohesion Evaluation Scales, FACES IV), were assessed in 164 Italian gay and lesbian young adults. Pearson correlation coefficients were calculated to assess the relation between family functioning and parental reaction to CO. The paired sample t-test was used to compare mothers and fathers' scores on the PPRS. Hierarchical multiple regression was conducted to analyze the relevance of each variable. No differences were found between mothers and fathers in their reaction to the disclosure. The analysis showed that a negative reaction to coming out was predicted by parents' right-wing political conservatism, strong religious beliefs, and higher scores in the scales Rigid and Enmeshed. Findings confirm that a negative parental reaction is the result of poor family resources to face a stressful situation and a strong belief in traditional values. These results have important implications in both clinical and social fields

A gold-containing drug against parasitic polyamine metabolism: the X-ray structure of trypanothione reductase from Leishmania infantum in complex with auranofin reveals a dual mechanism of enzyme inhibition

Auranofin is a gold(I)-containing drug in clinical use as an antiarthritic agent. Recent studies showed that auranofin manifests interesting antiparasitic actions very likely arising from inhibition of parasitic enzymes involved in the control of the redox metabolism. Trypanothione reductase is a key enzyme of Leishmania infantum polyamine-dependent redox metabolism, and a validated target for antileishmanial drugs. As trypanothione reductase contains a dithiol motif at its active site and gold(I) compounds are known to be highly thiophilic, we explored whether auranofin might behave as an effective enzyme inhibitor and as a potential antileishmanial agent. Notably, enzymatic assays revealed that auranofin causes indeed a pronounced enzyme inhibition. To gain a deeper insight into the molecular basis of enzyme inhibition, crystals of the auranofin-bound enzyme, in the presence of NADPH, were prepared, and the X-ray crystal structure of the auranofin–trypanothione reductase–NADPH complex was solved at 3.5 Å resolution. In spite of the rather low resolution, these data were of sufficient quality as to identify the presence of the gold center and of the thiosugar of auranofin, and to locate them within the overall protein structure. Gold binds to the two active site cysteine residues of TR, i.e. Cys52 and Cys57, while the thiosugar moiety of auranofin binds to the trypanothione binding site; thus auranofin appears to inhibit TR through a dual mechanism. Auranofin kills the promastigote stage of L. infantum at micromolar concentration; these findings will contribute to the design of new drugs against leishmaniasis