Nanovoid nucleation by vacancy aggregation and vacancy-cluster coarsening in high-purity metallic single crystals

A numerical model to estimate critical times required for nanovoid nucleation in high-purity aluminum single crystals subjected to shock loading is presented. We regard a nanovoid to be nucleated when it attains a size sufficient for subsequent growth by dislocation-mediated plasticity. Nucleation is assumed to proceed by means of diffusion-mediated vacancy aggregation and subsequent vacancy cluster coarsening. Nucleation times are computed by a combination of lattice kinetic Monte Carlo simulations and simple estimates of nanovoid cavitation pressures and vacancy concentrations. The domain of validity of the model is established by considering rate-limiting physical processes and theoretical strength limits. The computed nucleation times are compared to experiments suggesting that vacancy aggregation and cluster coarsening are feasible mechanisms of nanovoid nucleation in a specific subdomain of the pressure-strain rate-temperature space

Increase of Circulating Monocyte–Platelet Conjugates in Rheumatoid Arthritis Responders to IL-6 Blockage

Monocytes; Rheumatoid arthritis; TocilizumabMonocitos; Artritis reumatoide; TocilizumabMonòcits; Artritis reumatoide; TocilizumabPlatelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6.This study is supported by Instituto de Salud Carlos III and Fondos FEDER (PI17/00072 and PI20/00184)

Building Information Modeling for Cultural Heritage: The Management of Generative Process for Complex Historical Buildings

Building Information Modeling (BIM) enhances the sharing of information during the traditional process for new construction, but most of the time, it requires high levels of knowledge management for the historical digital model (H-BIM). The innovation in the Digital Cultural Heritage (DCH) domain is supported by the development of Information and Communications Technologies (ICT) and modern tools that are able to transmit morphological characteristics of the buildings in all their uniqueness. The latest research in the field of H-BIM shows a significant emergence of innovative methods and management initiatives for the generation of complex historical elements, leading to the confrontation of the paradigm of regularity (simple geometric shapes) with the new paradigm of complexity (historical building elements). This paper proves the benefits of the BIM for project management of the Centre Block of the Canadian Parliament in Ottawa, Ontario Canada, and shows the results obtained by the introduction of Advanced Modeling Techniques (AMT) during the generative process, reducing time and cost for the creation of the complex architectural and structural elements. The uniqueness of the forms of historical buildings is a real value to be transmitted throughout the building’s lifecycle with high Levels of Detail (LOD). Proper management of geometric primitives and Non-Uniform Rational Basis Spline (NURBS) models have guaranteed the conversion of spatial data (point clouds) from laser scanning and photogrammetry (geometric survey) into parametric applications. This paper explores the generative process of one of the most complex spaces within The Centre Block building of Parliament Hill—Confederation Hall

CONSTANS–FKBP12 interaction contributes to modulation of photoperiodic flowering in Arabidopsis

Flowering time is a key process in plant development. Photoperiodic signals play a crucial role in the floral transition in Arabidopsis thaliana, and the protein CONSTANS (CO) has a central regulatory function that is tightly regulated at the transcriptional and post-translational levels. The stability of CO protein depends on a light-driven proteasome process that optimizes its accumulation in the evening to promote the production of the florigen FLOWERING LOCUS T (FT) and induce seasonal flowering. To further investigate the post-translational regulation of CO protein we have dissected its interactome network employing in vivo and in vitro assays and molecular genetics approaches. The immunophilin FKBP12 has been identified in Arabidopsis as a CO interactor that regulates its accumulation and activity. FKBP12 and CO interact through the CCT domain, affecting the stability and function of CO. fkbp12 insertion mutants show a delay in flowering time, while FKBP12 overexpression accelerates flowering, and these phenotypes can be directly related to a change in accumulation of FT protein. The interaction is conserved between the Chlamydomonas algal orthologs CrCO–CrFKBP12, revealing an ancient regulatory step in photoperiod regulation of plant development.Ministerio de Ciencia BIO2014-52425-P, BIO2017-83629-RJunta de Andalucía P08-AGR-03582, BIO-281European Union GA83831

ONLINE COLLABORATION FOR SOUTH-NORTH HISTORIC SITE RECORDING TRAINING OF EMERGING PROFESSIONALS

This contribution offers insights into delivering a Historic Site Recording course entirely over the Internet using video conferencing and sharing tools. The opportunities and challenges will be described, and the approaches used to ensure meeting realistic learning outcomes by offering a meaningful student experience will provide digital tools and cloud services. The classroom was staged at the students’ homes. Immediate surroundings of their countries in Latin America (Argentina, Bolivia, Chile, Guatemala, Peru, and Mexico), and the teachers were based in Santiago (Chile), Ibague (Colombia), Barcelona (Spain), and Ottawa (Canada) and video conferencing, collaboration tools and social media made the connections. Two introductory courses for 13 weeks were delivered, followed by an advanced course in heritage recording tools. At the end of the introductory course, students provided a heritage recording proposal for a site in their own countries

RECREATING CULTURAL HERITAGE ENVIRONMENTS FOR VR USING PHOTOGRAMMETRY

In this paper, we propose a workflow for recreating places of cultural heritage in Virtual Reality (VR) using structure from motion (SfM) photogrammetry. The unique texture of heritage places makes them ideal for full photogrammetric capture. An optimized model is created from the photogrammetric data so that it is small enough to render in a real-time environment. The optimized model, combined with mesh maps (texture maps, normal maps, etc.) looks like the original high detail model. The capture of a whole space makes it possible to create a VR experience with six degrees of freedom (6DoF) that allows the user to explore the historic place. Creating these experiences can bring people to cultural heritage that is either endangered or too remote for some people to access. The workflow described in this paper will be demonstrated with the case study of Myin-pya-gu, an 11th century temple in Bagan, Myanmar

Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients

In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells ex vivo. In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC). Cytotoxicity assays were performed on bone marrow aspirates of 18 MM patients and 4 patients with monoclonal gammopathy of undetermined significance (MGUS). Expression levels of PD-1 on eNKs and PD-L1 on MM and MGUS cells were also quantified. Results indicate that most eNKs obtained using our expansion protocol express a low percentage of PD-1+ cells. UCB eNKs were highly cytotoxic against MM cells and addition of daratumumab or pembrolizumab did not further increase their cytotoxicity. PB eNKs, while effective against MM cells, were significantly more cytotoxic when combined with daratumumab. In a minority of cases, eNK cells showed a detectable population of PD1+ cells. This correlated with low cytotoxic activity, particularly in UCB eNKs. Addition of pembrolizumab did not restore their activity. Results indicate that UCB eNKs are to be preferentially used against MM in the absence of daratumumab while PB eNKs have significant cytotoxic advantage when combined with this mAb

yuDetecting the percent of peripheral blood mononuclear cells displaying p-STAT-3 in malignant glioma patients

<p>Abstract</p> <p>Background</p> <p>The signal transducer and activator of transcription 3 (STAT-3) is frequently overexpressed in cancer cells, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. The presence of phosphorylated STAT-3 (p-STAT-3) in the tumor can induce p-STAT-3 in tumor-associated immune cells that can return to the circulatory system. We hypothesized that the number of peripheral blood mononuclear cells (PBMCs) displaying p-STAT-3 would be increased in glioma patients, which would correlate with the extent of tumor-expressed p-STAT-3, and that higher p-STAT-3 levels in peripheral blood would correlate with a higher fraction of immune-suppressive regulatory T cells (Tregs).</p> <p>Methods</p> <p>We measured the percentage of PBMCs displaying p-STAT-3 in 19 healthy donors and 45 patients with primary brain tumors. The level of p-STAT-3 in tumor tissue was determined by immunohistochemistry. The degree of immune suppression was determined based on the fraction of Tregs in the CD4 compartment.</p> <p>Results</p> <p>Healthy donors had 4.8 ± 3.6% of PBMCs that expressed p-STAT-3, while the mean proportion of PBMCs displaying p-STAT-3 in patients with GBM was 11.8 ± 13.5% (<it>P </it>= 0.03). We did not observe a correlation by Spearman correlation between the degree of p-STAT-3 levels in the tumor and the percent of PBMCs displaying p-STAT-3. Furthermore, the percent of PBMCs displaying p-STAT-3 in glioma patients was not directly correlated with the fraction of Tregs in the CD4 compartment.</p> <p>Conclusion</p> <p>We conclude that the percent of PBMCs displaying p-STAT-3 may be increased in malignant glioma patients.</p

IMPACT OF VIRTUAL REALITY EXPERIENCE ON ACCESSIBILITY OF CULTURAL HERITAGE

Accessibility plays a main role among the aspects that contribute to the conservation of Cultural Heritage sites. Seismic stability, fragility of the artefacts, conflicts, deterioration, natural disasters, climate change and visitors’ impact are only some of the possible causes that might lead to the inaccessibility of a heritage site for both researchers and visitors.The increasing potential of Information and Communication Technologies (ICT) in the conservation field has resulted in the development of Augmented and Virtual reality (AR and VR) experiences. These ones can be very effective for what concerns the description of the visual experience, but also improve the understanding of a site and even became analytic research tools.This paper presents an inaccessible Buddhist temple in the Myanmar city of Bagan as a case study for the realization of a VR experience that aims at providing accessibility to knowledge and therefore a better understanding of the cultural value. In order to evaluate the effectiveness of the VR for this purpose, a user study has been conducted and its results are reported.</p