MICROSTRUCTURAL CHARACTERISAZTION OF THERMO-MECHANICAL TREATED TRIP STEELS

The increasing demand for the reduction of automobiles CO2 emissions for environmental preservation leads the automotive industries towards the mechanical components weight reduction. Sheet steels with multiphase microstructures exhibit favourable combinations of strength and ductility. The so called TRIP steels have a metastable microstructure that consists of a continuous ferrite matrix containing a dispersion of hard second phases martensite and bainite. These steels also contain retained austenite, at room temperature, that represents the source of the TRansformation Induced Plasticity effect. When the material is subjected to deformation step, the retained austenite transforms itself into martensite; the produced martensite delays the onset of necking resulting in a product with high total elongation, excellent formability and high crash energy absorption. In the present research the steel TRIP 800 zinc coated has been subjected to different thermo–mechanical treatments in order to evaluate the relation between microstructure of material and TRIP effects. Whit this aim the microstructural analysis has been performed and the evaluation of content of different phases has been made by means of the image analysis techniques. The relation among the strain level, the content of different phases, the thermal treatments and the work hardening properties of materials have been valued. Furthermore, it has been also highlighted the dependence of the bake hardening properties of material on the different thermo-mechanical treatments

Design Of Experiments for the optimization the process parameters of thixotropic aluminum alloy

The success of the thixoforming process depends on the possibility to confer to material, when it is found in the semisolid state, a microstructure characterized by globular particles of solid phase surrounded by a continuous film of liquid phase; such microstructure is obtainable through particular thermo-mechanical treatments. In the present research, in order to optimize the influence of process parameters in the step in which the thixotropic properties are conferred to the AA7075 aluminum alloy, the statistic technique of the Design Of Experiments (DOE) has been used. The advantages in the application of such technique are expressible in terms of reduction the times of development of process and more efficient use of resources. A Central Composite Design factorial plan with two levels has been realized to allow the evaluation of experimental error and to check the adequacy of the model. The experimental tests foreseen from the same plan have been therefore performed. Using the method of the response surfaces (RSM), the function of response has been formulated, and the analysis of the experimental data has been realized by the linear regression method. Finally, the analysis of variance (ANOVA) allowed to value the causes of variability of the results. Statistic test has been performed on the significance of single factors and their interactions

A new control parameter to predict micro‑warping‑induced job failure in LPBF of TI6AL4V titanium alloy

Laser powder bed fusion (LPBF) includes a few printing techniques widely used, in recent years, concerning the additive manufacturing of Ti6Al4V alloys. These produced parts, typically utilized in sectors such as aerospace and biomedical, are characterized by very high added value. It is therefore fundamental to identify the influence of process parameters typical of LPBF technology on the occurrence of warping leading to process failure. This study deals with the characterization of single-track and “micro-scale” level warping phenomena which may lead to protrusion of material over the powder bed and process failure before normal termination. This phenomenon was investigated as a function of process parameters, referring also to the strength and ductility characteristics of the manufactured samples. With this purpose, several samples were printed using variable process parameters both in terms of line energy density (LED) values and in terms of laser power and speed combinations such as to guarantee constant LED values. For the samples that did not show significant micro-warping phenomena, in addition to the transversal and longitudinal geometric characterization of the single track, tensile tests were performed to determine both the resistance of the material and the ductility characteristics. The single tracks, for given process parameters, were printed on a homogeneous material substrate. For every single track, a microstructural and morphological transverse and longitudinal characterization has been carried out and the measured geometrical features were correlated to the process parameters. The obtained results allowed the identification of a new threshold parameter, indicating the limit operating conditions beyond which significant warping phenomena and process failure occur

Niemann-Pick type C disease mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts

We analyzed Niemann-Pick type C disease 1 (NP44406) gene in 12 patients with Niemann-Pick type C disease by sequencing both cDNA obtained from fibroblasts and genomic DNA. All the patients were compound heterozygotes. We found 15 mutations, eight of which previously unreported. The comparison of cDNA and genomic DNA revealed discrepancies in some subjects. In two unrelated patients carrying the same mutations (P474L and nt 2972del2) only one mutant allele (P474L), was expressed in fibroblasts. The mRNA corresponding to the other allele was not detected even in cells incubated with cycloheximide. The promoter variants (−1026T/G and −1186T/C or −238 C/G), found to be in linkage with 2972del2 allele do not explain the lack of expression of this allele, as they were also found in control subjects. In another patient, (N1156S/Q922X) the N1156S allele was expressed in fibroblasts while the expression of the other allele was hardly detectable. In a fourth patient cDNA analysis revealed a point mutation in exon 20 (P1007A) and a 56 nt deletion in exon 22 leading to a frameshift and a premature stop codon. The first mutation was confirmed in genomic DNA; the second turned out to be a T→G transversion in exon 22, predicted to cause a missense mutation (V1141G). In fact, this transversion generates a donor splice site in exon 22, which causes an abnormal pre-mRNA splicing leading to a partial deletion of this exon. In some NPC patients, therefore, the comparison between cDNA and genomic DNA may reveal an unexpected expression of some mutant alleles of NPC1 gene

Information sources and knowledge on vaccination in a population from southern Italy: The ESCULAPIO project

Vaccine knowledge of the general population is shaped by different information sources and strongly influences vaccination attitudes and uptake. The CCM-Italian Ministry of Health ESCULAPIO project attempted to identify the role of such information sources, in order to address adequate strategies to improve information on vaccines and vaccine preventable diseases. In the present study, data on 632 adults from Southern Italy regarding information sources were collected, and their perceived and actual knowledge on vaccinations were compared and analyzed in relation to socio-demographic characteristics and information sources. The main reported reference sources were general practitioners (GPs) (42.5%) and pediatricians (33.1%), followed by mass media (24.1%) and the Internet (17.6%). A total of 45.4% reported they believed to be informed (45.4%), while those estimated to be truly informed were 43.8%. However, as showed in the multivariate logistic regression, people having the perception to be correctly informed ascribed their good knowledge to their profession in the health sector (Adj OR 2.28, CI 1.09–4.77, p < 0.05) and to friends/relatives/colleagues (AdjOR 6.25, CI 2.38–16.44, p < 0.001), while the non-informed population thought the responsibility had to be attributed to mass media (AdjOR 0.45, CI 0.22–0.92, p < 0.05). Those showing the real correct information, instead, were younger (AdjOR 1.64, CI 1.04–2.59, p < 0.05), and their main reference sources were pediatricians (AdjOR 1.63, CI 1.11–2.39, p < 0.05) and scientific magazines (Adj OR 3.39, CI 1.51–7.59, p < 0.01). Only 6% knew the “VaccinarSì” portal, developed to counter the widespred antivaccine websites in Italy. The post-survey significant increase of connections to “VaccinarSi” could be ascribed to the counselling performed during questionnaire administration. Strategies to improve information about vaccination should be addressed to fortifying healthcare workers knowledge in order to make them public health opinion leaders. General population should be provided with correct indications on trustworthy websites on vaccines to contrast false information supplied by anti-vaccinists on their own websites or social networks pages and on the mass media

“Oxaliplatin plus high dose folinic acid and 5-fluoruracil i.v. bolus (OXAFAFU) versus irinotecan plus high dose folinic acid and 5-fluoruracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: Southern Italy Cooperative Oncology Group trial 0103”

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients

Unmasking Determinants of Specificity in the Human Kinome

SummaryProtein kinases control cellular responses to environmental cues by swift and accurate signal processing. Breakdowns in this high-fidelity capability are a driving force in cancer and other diseases. Thus, our limited understanding of which amino acids in the kinase domain encode substrate specificity, the so-called determinants of specificity (DoS), constitutes a major obstacle in cancer signaling. Here, we systematically discover several DoS and experimentally validate three of them, named the αC1, αC3, and APE-7 residues. We demonstrate that DoS form sparse networks of non-conserved residues spanning distant regions. Our results reveal a likely role for inter-residue allostery in specificity and an evolutionary decoupling of kinase activity and specificity, which appear loaded on independent groups of residues. Finally, we uncover similar properties driving SH2 domain specificity and demonstrate how the identification of DoS can be utilized to elucidate a greater understanding of the role of signaling networks in cancer (Creixell et al., 2015 [this issue of Cell])

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only with high level of Ki67 (P <0.05). None of the samples from peripheral blood of 35 healthy female individuals were positive for MGB1 transcript. In contrast MGB1 mRNA expression was detected in three of 36 (8%) peripheral blood of BC patients. CONCLUSIONS: Our preliminary results demonstrate that the detection of MGB1 transcript in peripheral blood of BC patients was specific but with low sensitivity. MGB1 overexpression by itself or in combination with Ki67 might be considered an index of BC progression

SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

PhosTryp: a phosphorylation site predictor specific for parasitic protozoa of the family trypanosomatidae

<p>Abstract</p> <p>Background</p> <p>Protein phosphorylation modulates protein function in organisms at all levels of complexity. Parasites of the <it>Leishmania </it>genus undergo various developmental transitions in their life cycle triggered by changes in the environment. The molecular mechanisms that these organisms use to process and integrate these external cues are largely unknown. However <it>Leishmania </it>lacks transcription factors, therefore most regulatory processes may occur at a post-translational level and phosphorylation has recently been demonstrated to be an important player in this process. Experimental identification of phosphorylation sites is a time-consuming task. Moreover some sites could be missed due to the highly dynamic nature of this process or to difficulties in phospho-peptide enrichment.</p> <p>Results</p> <p>Here we present PhosTryp, a phosphorylation site predictor specific for trypansomatids. This method uses an SVM-based approach and has been trained with recent <it>Leishmania </it>phosphosproteomics data. PhosTryp achieved a 17% improvement in prediction performance compared with Netphos, a non organism-specific predictor. The analysis of the peptides correctly predicted by our method but missed by Netphos demonstrates that PhosTryp captures <it>Leishmania</it>-specific phosphorylation features. More specifically our results show that <it>Leishmania </it>kinases have sequence specificities which are different from their counterparts in higher eukaryotes. Consequently we were able to propose two possible <it>Leishmania</it>-specific phosphorylation motifs.</p> <p>We further demonstrate that this improvement in performance extends to the related trypanosomatids <it>Trypanosoma brucei </it>and <it>Trypanosoma cruzi</it>. Finally, in order to maximize the usefulness of PhosTryp, we trained a predictor combining all the peptides from <it>L. infantum, T. brucei and T. cruzi</it>.</p> <p>Conclusions</p> <p>Our work demonstrates that training on organism-specific data results in an improvement that extends to related species. PhosTryp is freely available at <url>http://phostryp.bio.uniroma2.it</url></p