Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration. The breast tissue is modelled as a neo-Hookean material and gravity is considered as the main source of deformation in the original images. In addition to gravity, our framework successively applies image derived forces directly into the unloading simulation in place of a subsequent image registration step. This results in a biomechanically constrained deformation. Using a finite difference scheme avoids an explicit meshing step and enables simulations to be performed directly in the image space. The explicit time integration scheme allows the motion at the interface between chest and breast to be constrained along the chest wall. The feasibility and accuracy of the approach presented here was assessed by measuring the target registration error (TRE) using a numerical phantom with known ground truth deformations, nine clinical prone MRI and supine CT image pairs, one clinical prone-supine CT image pair and four prone-supine MRI image pairs. The registration reduced the mean TRE for the numerical phantom experiment from initially 19.3 to 0.9 mm and the combined mean TRE for all fourteen clinical data sets from 69.7 to 5.6 mm

Osteoinduction in human fat derived stem cells by recombinant human bone morphogenetic protein-2 produced in Escherichia coli

Bioactive recombinant human bone morphogenetic protein-2 (rhBMP-2) was obtained using Escherichia coli pET-25b expression system: 55 mg purified rhBMP-2 were achieved per g cell dry wt, with up to 95% purity. In murine C2C12 cell line, rhBMP-2 induced an increase in the transcription of Smads and of osteogenic markers Runx2/Cbfa1 and Osterix, measured by semi-quantitative RT-PCR. Bioassays performed in human fat-derived stem cells showed an increased activity of the early osteogenic marker, alkaline phosphatase, and the absence of cytotoxicity

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth

Carcass persistence and detectability : reducing the uncertainty surrounding wildlife-vehicle collision surveys

Carcass persistence time and detectability are two main sources of uncertainty on roadkill surveys. In this study, we evaluate the influence of these uncertainties on roadkill surveys and estimates. To estimate carcass persistence time, three observers (including the driver) surveyed 114km by car on a monthly basis for two years, searching for wildlife-vehicle collisions (WVC). Each survey consisted of five consecutive days. To estimate carcass detectability, we randomly selected stretches of 500m to be also surveyed on foot by two other observers (total 292 walked stretches, 146 km walked). We expected that body size of the carcass, road type, presence of scavengers and weather conditions to be the main drivers influencing the carcass persistence times, but their relative importance was unknown. We also expected detectability to be highly dependent on body size. Overall, we recorded low median persistence times (one day) and low detectability (<10%) for all vertebrates. The results indicate that body size and landscape cover (as a surrogate of scavengers' presence) are the major drivers of carcass persistence. Detectability was lower for animals with body mass less than 100g when compared to carcass with higher body mass. We estimated that our recorded mortality rates underestimated actual values of mortality by 2±10 fold. Although persistence times were similar to previous studies, the detectability rates here described are very different from previous studies. The results suggest that detectability is the main source of bias across WVC studies. Therefore, more than persistence times, studies should carefully account for differing detectability when comparing WVC studies

P-selectin glycoprotein ligand 1 promotes T cell lymphoma development and dissemination

P-selectin glycoprotein ligand-1 (PSGL-1) is a membrane-bound glycoprotein expressed in lymphoid and myeloid cells. It is a ligand of P-, E- and L-selectin and is involved in T cell trafficking and homing to lymphoid tissues, among other functions. PSGL-1 expression has been implicated in different lymphoid malignancies, so here we aimed to evaluate the involvement of PSGL-1 in T cell lymphomagenesis and dissemination. PSGL-1 was highly expressed at the surface of human and mouse T cell leukemia and lymphoma cell lines. To assess its impact on T cell malignancies, we stably expressed human PSGL-1 (hPSGL-1) in a mouse thymic lymphoma cell line, which expresses low levels of endogenous PSGL-1 at the cell surface. hPSGL-1-expressing lymphoma cells developed subcutaneous tumors in athymic nude mice recipients faster than control empty vector or parental cells. Moreover, the kidneys, lungs and liver of tumor-bearing mice were infiltrated by hPSGL-1-expressing malignant T cells. To evaluate the role of PSGL-1 in lymphoma cell dissemination, we injected intravenously control and hPSGL-1-expressing lymphoma cells in athymic mice. Strikingly, PSGL-1 expression facilitated disease infiltration of the kidneys, as determined by histological analysis and anti-CD3 immunohistochemistry. Together, these results indicate that PSGL-1 expression promotes T cell lymphoma development and dissemination to different organs.We thank Roger McEver, José M Almendral, Hind Medyouf, João T Barata and Neil D Perkins for providing reagents and cells, André Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Fundação para a Ciência e a Tecnologia (Portugal), European Social Fund , European Regional Development Fund ( PTDC/SAU-OBD/103336/2008 , PTDC/MED-ONC/32592/2017 , UID/BIM/04773/2013 , NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead GÉNESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ). We thank Roger McEver, Jos? M Almendral, Hind Medyouf, Jo?o T Barata and Neil D Perkins for providing reagents and cells, Andr? Mozes (CBMR Flow Cytometry Unit) for technical assistance and Sara Miranda and Nuno Bastos for immunohistochemistry technical assistance. This work was supported by Funda??o para a Ci?ncia e a Tecnologia (Portugal), European Social Fund, European Regional Development Fund (PTDC/SAU-OBD/103336/2008, PTDC/MED-ONC/32592/2017, UID/BIM/04773/2013, NORTE-01-0145-FEDER-000029 and POCI-01-0145-FEDER-007274 grants, IF/00056/2012 contract to NRdS and SFRH/BD/147979/2019 fellowship to JLP), and Gilead Sciences Portugal (Programa Gilead G?NESE PGG/038/2017 grant). The authors acknowledge the support of the i3S Scientific Platform Histology and Electron Microscopy, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122)