Comparison of theory with experiment in the phenomenon of wing flutter

Direct measurements were undertaken at the Aeronautics Laboratory in Turin of the aerodynamic actions on an oscillating wing. The tests conducted had as their essential object the examination of the operation of apparatus designed for this measurement. The values experimentally obtained for the aerodynamic coefficients are in good agreement with the theory of oscillatory motion of the wing of finite span and show clear deviation from the values obtained by theory of plane motion

Study of MicroPattern Gaseous detectors with novel nanodiamond based photocathodes for single photon detection in EIC RICH

Identification of high momentum hadrons at the future EIC is crucial, gaseous RICH detectors are therefore viable option. Compact collider setups impose to construct RICHes with small radiator length, hence significantly limiting the number of detected photons. More photons can be detected in the far UV region, using a windowless RICH approach. QE of CsI degrades under strong irradiation and air contamination. Nanodiamond based photocathodes (PCs) are being developed as an alternative to CsI. Recent development of layers of hydrogenated nanodiamond powders as an alternative photosensitive material and their performance, when coupled to the THick Gaseous Electron Multipliers (THGEM)-based detectors, are the objects of an ongoing R\&D. We report about the initial phase of our studies.Comment: 3 pages, 5 figures, RICH2018 conference proceedin

Polycrystalline diamond films grown by MWPECVD technique and application in photocathodes

Diamond is an extremely interesting material for photoemission applications, due to the negative electron affinity which can be obtained after suitable surface treatments. In the present work, two sets of polycrystalline diamond films, characterized by dif-ferent thickness and deposition conditions, are ana-lyzed. In particular, the relationship among the grain size, the amount of non-diamond carbon (sp2) located at the grain boundaries and the film sensitivity as a photocathode has been found and carefully investi-gated. The photoemission yield in the UV range has been evaluated for all the samples, before and after hydrogenation process, and after air exposure. The critical parameter for the photocathode performances has been found not to be the film thickness, but the properties of polycrystalline diamond films, tunable with the plasma modulation and the methane percent-age in the gas mixture

Inhibition of CD73 improves B cell-mediated anti-tumor immunity in a mouse model of melanoma.

CD73 is a cell surface enzyme that suppresses T cell-mediated immune responses by producing extracellular adenosine. Growing evidence suggests that targeting CD73 in cancer may be useful for an effective therapeutic outcome. In this study, we demonstrate that administration of a specific CD73 inhibitor, adenosine 5'-(α,β-methylene)diphosphate (APCP), to melanoma-bearing mice induced a significant tumor regression by promoting the release of Th1- and Th17-associated cytokines in the tumor microenvironment. CD8+ T cells were increased in melanoma tissue of APCP-treated mice. Accordingly, in nude mice APCP failed to reduce tumor growth. Importantly, we observed that after APCP administration, the presence of B cells in the melanoma tissue was greater than that observed in control mice. This was associated with production of IgG2b within the melanoma. Depletion of CD20+ B cells partially blocked the anti-tumor effect of APCP and significantly reduced the production of IgG2b induced by APCP, implying a critical role for B cells in the anti-tumor activity of APCP. Our results also suggest that APCP could influence B cell activity to produce IgG through IL-17A, which significantly increased in the tumor tissue of APCP-treated mice. In support of this, we found that in melanoma-bearing mice receiving anti-IL-17A mAb, the anti-tumor effect of APCP was ablated. This correlated with a reduced capacity of APCP-treated mice to mount an effective immune response against melanoma, as neutralization of this cytokine significantly affected both the CD8+ T cell- and B cell-mediated responses. In conclusion, we demonstrate that both T cells and B cells play a pivotal role in the APCP-induced anti-tumor immune response

Safety and tolerability of antipsychotic drugs in pediatric patients: data from a 1-year naturalistic study

Background: Antipsychotic drugs (APs) are increasingly used to treat a variety of psychiatric disorders in children and adolescents. However, their safety and tolerability profiles, when used in a developmental age context, show different characteristics from the ones observed in adult patients. Treatment with APs in pediatric patients is often long-term. However, the tolerability data regarding these patients mostly derive from short-term studies. Methods: Starting from April 2017, for a 1-year period, patients between 4 and 18 years of age followed by five units of developmental age neuropsychiatry, who initiated a treatment with at least an AP (ATC class N05A) were included into the study. Patient-related data have been collected at baseline and regularly thereafter, as allowed by the clinical routine. Changes to continuous variables over time have been analyzed using a linear mixed model in subsamples of our population treated with risperidone or aripiprazole. Results: During the observation period, 158 patients were initially enrolled, but only 116 completed 12 months of therapy with an AP. Risperidone was the most used AP (n = 52) followed by aripiprazole (n = 44) and olanzapine (n = 7). For both the aripiprazole and risperidone groups, the mean body mass index (BMI) (P < 0.001 for both groups) and heart rate (P = 0.026 for aripiprazole group and P < 0.001 for the risperidone one) values significantly increased over time. The mean prolactin concentration value significantly increased over time only in the risperidone group (P = 0.04). Eighty-six patients experienced at least one adverse drug reaction (ADR), accounting for a total of 238 specific reactions, with the most frequent being weight gain (n = 34), increased serum prolactin levels (n = 21), hyperphagia (n = 20), and hypercholesterolemia (n = 14). Among these, only 24 ADRs were classifiable as serious. Conclusions: The results of this study confirm that risperidone and aripiprazole are relatively well-tolerated therapeutic options for the treatment of a variety of psychiatric disorders in pediatric patients. However, in findings such as statistically significant increments of BMI and heart rate mean values, the variations over time in prolactin levels observed with risperidone and the differences between the two drugs remark the necessity of systematic monitoring

Aluminum to titanium laser welding-brazing in V-shaped grooveI

Laser assisted joining of AA5754 aluminum alloy to T40 titanium with use of Al-Si filler wires was carried out. Continuous Yb:YAG laser beam was shaped into double spot tandem and defocalized to cover larger interaction zone in V shaped groove. Experimental design method was applied to study the influence of operational parameters on the tensile properties of the joints. Microstructure examination and fractography study were carried out to understand the relation between local phase content and fracture mode. Within defined window of operational parameters, statistically important factors that influenced the strength of T40 to AA5754 joints in V groove configuration were Si content in the filler metal and groove opening angle on T40 side. The best quality joint showed joint coefficient of 90% (or 200 MPa of apparent UTS). Tensile strength of the joints was found to be determined by the proportion between well-developed and under-developed reaction zones of T40/melted zone interface. The formation of 2–25 μm thick Si-rich interlayers composed by Ti5Si3 and τ2 proved to enhance the strength of brazed interface. The creation of very thin (<0.5 μm) Si-rich layers at the bottom of the groove was found not sufficient to establish mechanical continuity of the joint and thus should be avoided

The Genotype of Early-Transmitting HIV gp120s Promotes α4β7 –Reactivity, Revealing α4β7+/CD4+ T cells As Key Targets in Mucosal Transmission

Mucosal transmission of HIV is inefficient. The virus must breach physical barriers before it infects mucosal CD4+ T cells. Low-level viral replication occurs initially in mucosal CD4+ T cells, but within days high-level replication occurs in Peyer's patches, the gut lamina propria and mesenteric lymph nodes. Understanding the early events in HIV transmission may provide valuable information relevant to the development of an HIV vaccine. The viral quasispecies in a donor contracts through a genetic bottleneck in the recipient, such that, in low-risk settings, infection is frequently established by a single founder virus. Early-transmitting viruses in subtypes A and C mucosal transmission tend to encode gp120s with reduced numbers of N-linked glycosylation sites at specific positions throughout the V1-V4 domains, relative to typical chronically replicating isolates in the donor quasispecies. The transmission advantage gained by the absence of these N-linked glycosylation sites is unknown. Using primary α4β7+/CD4+ T cells and a flow-cytometry based steady-state binding assay we show that the removal of transmission-associated N-linked glycosylation sites results in large increases in the specific reactivity of gp120 for integrin- α4β7. High-affinity for integrin α4β7, although not found in many gp120s, was observed in early-transmitting gp120s that we analyzed. Increased α4β7 affinity is mediated by sequences encoded in gp120 V1/V2. α4β7-reactivity was also influenced by N-linked glycosylation sites located in C3/V4. These results suggest that the genetic bottleneck that occurs after transmission may frequently involve a relative requirement for the productive infection of α4β7+/CD4+ T cells. Early-transmitting gp120s were further distinguished by their dependence on avidity-effects to interact with CD4, suggesting that these gp120s bear unusual structural features not present in many well-characterized gp120s derived from chronically replicating viruses. Understanding the structural features that characterize early-transmitting gp120s may aid in the design of an effective gp120-based subunit vaccine

Guidelines and Recommendations on the Use of Higher OrderFinite Elements for Bending Analysis of Plates

This paper compares and evaluates various plate finite elements to analyse the static response of thick and thin plates subjected to different loading and boundary conditions. Plate elements are based on different assumptions for the displacement distribution along the thickness direction. Classical (Kirchhoff and Reissner-Mindlin), refined (Reddy and Kant), and other higher-order displacement fields are implemented up to fourth-order expansion. The Unified Formulation UF by the first author is used to derive finite element matrices in terms of fundamental nuclei which consist of 3 × 3 arrays. The MITC4 shear-locking free type formulation is used for the FE approximation. Accuracy of a given plate element is established in terms of the error vs. thickness-to-length parameter. A significant number of finite elements for plates are implemented and compared using displacement and stress variables for various plate problems. Reduced models that are able to detect the 3D solution are built and a Best Plate Diagram (BPD) is introduced to give guidelines for the construction of plate theories based on a given accuracy and number of terms. It is concluded that the UF is a valuable tool to establish, for a given plate problem, the most accurate FE able to furnish results within a certain accuracy range. This allows us to obtain guidelines and recommendations in building refined elements in the bending analysis of plates for various geometries, loadings, and boundary conditions

Nanodiamond photocathodes for MPGD-based single photon detectors at future EIC

The design of a Ring Imaging CHerenkov (RICH) detector for the identification of high momentum particles at the future Electron Ion Collider (EIC) is extremely challenging by using current technology. Compact collider setups impose to construct RICH with short radiator length, hence limiting the number of generated photons. The number of detected photons can be increased by selecting the far UV region. As standard fused-silica windows is opaque below 165 nm, a windowless RICH can be a possible approach. CsI is widely used photocathode (PC) for photon detection in the far UV range. Due to its hygroscopic nature it is very delicate to handle. In addition, its Quantum Efficiency (QE) degrades in high intensity ion fluxes. These are the key reasons to quest for novel PC with sensitivity in the far UV region. Recent development of layers of hydrogenated nanodiamond powders as an alternative PC material and their performance, when coupled to the THick Gaseous Electron Multipliers (THGEM)-based detectors, are the objects of an ongoing R\&D. We report here some preliminary results on the initial phase of these studies.Comment: 6 pages, 5 figures, MPGD-2019 La Rochelle, Proceedin

HIV-1 envelope, integrins and co-receptor use in mucosal transmission of HIV

It is well established that HIV-1 infection typically involves an interaction between the viral envelope protein gp120/41 and the CD4 molecule followed by a second interaction with a chemokine receptor, usually CCR5 or CXCR4. In the early stages of an HIV-1 infection CCR5 using viruses (R5 viruses) predominate. In some viral subtypes there is a propensity to switch to CXCR4 usage (X4 viruses). The receptor switch occurs in ~ 40% of the infected individuals and is associated with faster disease progression. This holds for subtypes B and D, but occurs less frequently in subtypes A and C. There are several hypotheses to explain the preferential transmission of R5 viruses and the mechanisms that lead to switching of co-receptor usage; however, there is no definitive explanation for either. One important consideration regarding transmission is that signaling by R5 gp120 may facilitate transmission of R5 viruses by inducing a permissive environment for HIV replication. In the case of sexual transmission, infection by HIV requires the virus to breach the mucosal barrier to gain access to the immune cell targets that it infects; however, the immediate events that follow HIV exposure at genital mucosal sites are not well understood. Upon transmission, the HIV quasispecies that is replicating in an infected donor contracts through a “genetic bottleneck”, and often infection results from a single infectious event. Many details surrounding this initial infection remain unresolved. In mucosal tissues, CD4+ T cells express high levels of CCR5, and a subset of these CD4+/CCR5high cells express the integrin α4β7, the gut homing receptor. CD4+/CCR5high/ α4β7high T cells are highly susceptible to infection by HIV-1 and are ideal targets for an efficient productive infection at the point of transmission. In this context we have demonstrated that the HIV-1 envelope protein gp120 binds to α4β7 on CD4+ T cells. On CD4+/CCR5high/ α4β7high T cells, α4β7 is closely associated with CD4 and CCR5. Furthermore, α4β7 is ~3 times the size of CD4 on the cell surface, that makes it a prominent receptor for an efficient virus capture. gp120-α4β7 interactions mediate the activation of the adhesion-associated integrin LFA-1. LFA-1 facilitates the formation of virological synapses and cell-to-cell spread of HIV-1. gp120 binding to α4β7 is mediated by a tripeptide located in the V1/V2 domain of gp120. Of note, the V1/V2 domain of gp120 has been linked to variations in transmission fitness among viral isolates raising the intriguing possibility that gp120-α4β7 interactions may be linked to transmission fitness. Although many details remain unresolved, we hypothesize that gp120-α4β7 interactions play an important role in the very early events following sexual transmission of HIV and may have important implication in the design of vaccine strategies for the prevention of acquisition of HIV infectio