Monte Carlo-based 3D surface point cloud volume estimation by exploding local cubes faces

This article proposes a state-of-the-art algorithm for estimating the 3D volume enclosed in a surface point cloud via a modified extension of the Monte Carlo integration approach. The algorithm consists of a pre-processing of the surface point cloud, a sequential generation of points managed by an affiliation criterion, and the final computation of the volume. The pre-processing phase allows a spatial reorientation of the original point cloud, the evaluation of the homogeneity of its points distribution, and its enclosure inside a rectangular parallelepiped of known volume. The affiliation criterion using the explosion of cube faces is the core of the algorithm, handles the sequential generation of points, and proposes the effective extension of the traditional Monte Carlo method by introducing its applicability to the discrete domains. Finally, the final computation estimates the volume as a function of the total amount of generated points, the portion enclosed within the surface point cloud, and the parallelepiped volume. The developed method proves to be accurate with surface point clouds of both convex and concave solids reporting an average percentage error of less than 7 %. It also shows considerable versatility in handling clouds with sparse, homogeneous, and sometimes even missing points distributions. A performance analysis is presented by testing the algorithm on both surface point clouds obtained from meshes of virtual objects as well as from real objects reconstructed using reverse engineering techniques

Transcriptomic landscape of skin lesions in cutaneous leishmaniasis reveals a strong CD8(+) T cell immunosenescence signature linked to immunopathology

The severity of lesions that develop in patients infected by Leishmania braziliensis is mainly associated with a highly cytotoxic and inflammatory cutaneous environment. Recently, we demonstrated that senescent T and NK cells play a role in the establishment and maintenance of this tissue inflammation. Here, we extended those findings using transcriptomic analyses that demonstrate a strong co-induction of senescence and pro-inflammatory gene signatures in cutaneous leishmaniasis (CL) lesions. The senescence-associated signature was characterized by marked expression of key genes such as ATM, Sestrin 2, p16, p21 and p38. The cell type identification from deconvolution of bulk sequencing data showed that the senescence signature was linked with CD8+ effector memory and TEMRA subsets and also senescent NK cells. A key observation was that the senescence markers in the skin lesions are age-independent of patients and were correlated with lesion size. Moreover, a striking expression of the senescence-associated secretory phenotype (SASP), pro-inflammatory cytokine and chemokines genes was found within lesions that were most strongly associated with the senescent CD8 TEMRA subset. Collectively, our results confirm that there is a senescence transcriptomic signature in CL lesions and supports the hypothesis that lesional senescent cells have a major role in mediating immunopathology of the disease

Sestrins induce natural killer function in senescent-like CD8(+) T cells

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8⁺ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27⁻CD28⁻CD8⁺ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27⁻CD28⁻CD8⁺ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27⁻CD28⁻CD8⁺ T cells to acquire a broad-spectrum, innate-like killing activity

Circulating Senescent T Cells Are Linked to Systemic Inflammation and Lesion Size During Human Cutaneous Leishmaniasis

Leishmania (Viannia) braziliensis induces American tegumentary leishmaniasis that ranges in severity from the milder form, cutaneous (CL) to severe disseminated cutaneous leishmaniasis. Patients with CL develop a cell-mediated Th1 immune response accompanied by production of inflammatory cytokines, which contribute to parasite control and pathogenesis of disease. Here, we describe the accumulation of circulating T cells with multiple features of telomere dependent-senescence including elevated expression of CD57, KLRG-1, and γH2AX that have short telomeres and low hTERT expression during cutaneous L. braziliensis infection. This expanded population of T cells was found within the CD45RA+CD27− (EMRA) subset and produced high levels of inflammatory cytokines, analogous to the senescence-associated secretory profile (SASP) that has been described in senescent non-lymphoid cells. There was a significant correlation between the accumulation of these cells and the extent of systemic inflammation, suggesting that they are involved in the inflammatory response in this disease. Furthermore, these cells expressed high level of the skin homing receptor CLA and there was a highly significant correlation between the number of these cells in the circulation and the size of the Leishmania-induced lesions in the skin. Collectively our results suggest that extensive activation during the early stages of leishmaniasis drives the senescence of T cells with the propensity to home to the skin. The senescence-related inflammatory cytokine secretion by these cells may control the infection but also contribute to the immunopathology in the disease

Cohabitation : the Pan-America View

In this concluding chapter we reflect on a series of issues of both a methodological and substantive nature encountered in this research project. Firstly, we must realize that the use of individual census records not only opened vast possibilities, but also entails a number of limitations. Secondly, the very large sample sizes allowed for the disaggregation of national trends into far more detailed spatial, ethnic and educational patterns. This, in its turn, allowed us to adopt a "geo-historical" view of the rise of cohabitation for almost the entire American continent, from Alaska to Tierra del Fuego. Furthermore, statistical analyses could be performed at the individual and contextual levels simultaneously. Results show that the effects of social stratification, religion and ethnicity are continuing to be of major importance. This not only holds at the individual level, but at the contextual level as well. Nevertheless, an entirely new wave of change started rolling over the pre-existing patterns from the 1970s onward. These trends are following a firm course, irrespective of the economic ups and downs. The Americas, as opposed to many Asian societies and Africa, are now following in the European footsteps, be it with their own distinct and path-dependent characteristics associated with regionally varying historical antecedents