Coupling sensitive \u3cem\u3ein vitro\u3c/em\u3e and in silico techniques to assess cross-reactive CD4\u3csup\u3e+\u3c/sup\u3e T cells against the swine-origin H1N1 influenza virus

The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role in protecting against the pandemic H1N1 in the absence of cross-reactive humoral immunity. In a published study, we used an immunoinformatics approach to predict a number of CD4+ T cell epitopes are conserved between the 2008–2009 seasonal H1N1 vaccine strain and pandemic H1N1 (A/California/04/2009) hemagglutinin proteins. Here, we provide results from biological studies using PBMCs from human donors not exposed to the pandemic virus to demonstrate that pre-existing CD4+ T cells can elicit cross-reactive effector responses against the pandemic H1N1 virus. As well, we show our computational tools were 80–90% accurate in predicting CD4+ T cell epitopes and their HLA-DRB1-dependent response profiles in donors that were chosen at random for HLA haplotype. Combined, these results confirm the power of coupling immunoinformatics to define broadly reactive CD4+ T cell epitopes with highly sensitive in vitro biological assays to verify these in silico predictions as a means to understand human cellular immunity, including cross-protective responses, and to define CD4+ T cell epitopes for potential vaccination efforts against future influenza viruses and other pathogens

Further Confirmation of Broadly Conserved, Highly Immunogenic Cross-Clade HIV CTL Epitopes for Inclusion in the GAIA HIV Vaccine

Poster Presentation From AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 201

Inoculating an agile company with user-centred design: an empirical study

We present an empirical study on facilitating the adoption of user-centred design (UCD) in small Agile companies. To this end, we introduced a curated set of qualitative design practices in an Agile organisation, engaging developers in a lightweight series of workshops. Our results suggest that the approach followed enhanced internal communication and promoted a concrete shift towards a more user-centred perspective. However, the presence of a predominant non-Agile customer seems to have limited potential benefits. © The Author(s) 2017

The impact of multidisciplinary team management on outcome of hepatic resection in liver-limited colorectal metastases

Hepatic resection is the gold standard treatment for patients affected by liver-limited colorectal metastases. Reports addressing the impact of multidisciplinary team (MDT) evaluation on survival are controversial. The aim of this study was to evaluate the benefit of MDT management in these patients in our Institution experience. The objective of the analysis was to compare survivals of patients managed within our MDT (MDT cohort) to those of patients referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Of the 523 patients, 229 were included in the MDT cohort and 294 in the non-MDT cohort. No difference between the two groups was found in terms of median overall survival (52.5 vs 53.6 months; HR 1.13; 95% CI, 0.88–1.45; p = 0.344). In the MDT cohort there was a higher number of metastases (4.5 vs 2.7; p < 0.0001). The median duration of chemotherapy was lower in MDT patients (8 vs 10 cycles; p < 0.001). Post-operative morbidity was lower in the MDT cohort (6.2 vs 21.5%; p < 0.001). One hundred and ninety-seven patients in each group were matched by propensity score and no significant difference was observed between the two groups in terms of OS and DFS. Our study does not demonstrate a survival benefit from MDT management, but it allows surgery to patients with a more advanced disease. MDT assessment reduces the median duration of chemotherapy and post-operative morbidities

Designing Playful Games and Applications to Support Science Centers Learning Activities

In recent years there has been a renewed interest on science, technology, engineering, and mathematics (STEM) education. Following this interest, science centers\u27 staff started providing technology enhanced informal STEM education experiences. The use of well-designed mobile and ubiquitous forms of technology to enrich informal STEM education activities is an essential success factor. The goal of our research is to investigate how technology applications can be better used and developed for taking full advantage of the opportunities and challenges they provide for students learning about STEM concepts. In our approach, we have conducted a series of interviews with experts from science center curating and outdoor learning activities development, with the final goal of exploring and improving current learning environments and practices. This paper presents the development of set of design considerations for the development of STEM games and applications of young students. An initial set of best practices was first developed through semi-structures interviews with experts; and afterwards, by employing content analysis, a revised set of considerations was obtained. These results are useful for STEM education teachers, curriculum designers, curators and developers for K-12 education environments

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table

The low energy spectrum of TeO2 bolometers: results and dark matter perspectives for the CUORE-0 and CUORE experiments

We collected 19.4 days of data from four 750 g TeO2 bolometers, and in three of them we were able to set the energy threshold around 3 keV using a new analysis technique. We found a background rate ranging from 25 cpd/keV/kg at 3 keV to 2 cpd/keV/kg at 25 keV, and a peak at 4.7 keV. The origin of this peak is presently unknown, but its presence is confirmed by a reanalysis of 62.7 kg.days of data from the finished CUORICINO experiment. Finally, we report the expected sensitivities of the CUORE0 (52 bolometers) and CUORE (988 bolometers) experiments to a WIMP annual modulation signal.Comment: 9 pages, 10 figure

S4 Flavor Symmetry and Fermion Masses: Towards a Grand Unified theory of Flavor

Pursuing a bottom-up approach to explore which flavor symmetry could serve as an explanation of the observed fermion masses and mixings, we discuss an extension of the standard model (SM) where the flavor structure for both quarks and leptons is determined by a spontaneously broken S4 and the requirement that its particle content is embeddable simultaneously into the conventional SO(10) grand unified theory (GUT) and a continuous flavor symmetry G_f like SO(3)_f or SU(3)_f. We explicitly provide the Yukawa and the Higgs sector of the model and show its viability in two numerical examples which arise as small deviations from rank one matrices. In the first case, the corresponding mass matrix is democratic and in the second one only its 2-3 block is non-vanishing. We demonstrate that the Higgs potential allows for the appropriate vacuum expectation value (VEV) configurations in both cases, if CP is conserved. For the first case, the chosen Yukawa couplings can be made natural by invoking an auxiliary Z2 symmetry. The numerical study we perform shows that the best-fit values for the lepton mixing angles theta_12 and theta_23 can be accommodated for normal neutrino mass hierarchy. The results for the quark mixing angles turn out to be too small. Furthermore the CP-violating phase delta can only be reproduced correctly in one of the examples. The small mixing angle values are likely to be brought into the experimentally allowed ranges by including radiative corrections. Interestingly, due to the S4 symmetry the mass matrix of the right-handed neutrinos is proportional to the unit matrix.Comment: 27 pages, published version with minor change

New Cuoricino Results and Status of CUORE

CUORICINO is an array of 62 TeO2 bolometers with a total mass of 40.7 kg (11.2 kg of 130Te), operated at about 10 mK to search for ββ(0ν) of 130Te. The detectors are organized as a 14-story tower and intended as a slightly modified version of one of the 19 towers of the CUORE project, a proposed tightly packed array of 988 TeO2 bolometers (741 kg of total mass of TeO2) for ultralow-background searches on neutrinoless double-beta decay, cold dark matter, solar axions, and rare nuclear decays. Started in April 2003 at the Laboratori Nazionali del Gran Sasso (LNGS), CUORICINO data taking was stopped in November 2003 to repair the readout wiring system of the 62 bolometers. Restarted in spring 2004, CUORICINO is presently the most sensitive running experiment on neutrinoless double-beta decay. No evidence for ββ(0ν) decay has been found so far and a new lower limit, T 1 2/0ν ≥ 1.8 × 1024 yr (90% C.L.), is set, corresponding to 〈m ν〉 ≤ 0.2–1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis. Detector performance, operational procedures, and background analysis results are reviewed. The expected performance and sensitivity of CUORE is also discussed