Patient-specific image-based computer simulation for theprediction of valve morphology and calcium displacement after TAVI with the Medtronic CoreValve and the Edwards SAPIEN valve

AIMS: Our aim was to validate patient-specific software integrating baseline anatomy and biomechanical properties of both the aortic root and valve for the prediction of valve morphology and aortic leaflet calcium displacement after TAVI. METHODS AND RESULTS: Finite element computer modelling was performed in 39 patients treated with a Medtronic CoreValve System (MCS; n=33) or an Edwards SAPIEN XT (ESV; n=6). Quantitative axial frame morphology at inflow (MCS, ESV) and nadir, coaptation and commissures (MCS) was compared between multislice computed tomography (MSCT) post TAVI and a computer model as well as displacement of the aortic leaflet calcifications, quantified by the distance between the coronary ostium and the closest calcium nodule. Bland-Altman analysis revealed a strong correlation between the observed (MSCT) and predicted frame dimensions, although small differences were detected for, e.g., Dmin at the inflow (mean±SD MSCT vs. MODEL: 21.6±2.4 mm vs. 22.0±2.4 mm; difference±SD: -0.4±1.3 mm, p<0.05) and Dmax (25.6±2.7 mm vs. 26.2±2.7 mm; difference±SD: -0.6±1.0 mm, p<0.01). The observed and predicted calcium displacements were highly correlated for the left and right coronary ostia (R2=0.67 and R2=0.71, respectively p<0.001). CONCLUSIONS: Dedicated software allows accurate prediction of frame morphology and calcium displacement after valve implantation, which may help to improve outcome

Simultaneous co-localized super-resolution fluorescence microscopy and atomic force microscopy: combined SIM and AFM platform for the life sciences

Correlating data from different microscopy techniques holds the potential to discover new facets of signaling events in cellular biology. Here we report for the first time a hardware set-up capable of achieving simultaneous co-localized imaging of spatially correlated far-field super-resolution fluorescence microscopy and atomic force microscopy, a feat only obtained until now by fluorescence microscopy set-ups with spatial resolution restricted by the Abbe diffraction limit. We detail system integration and demonstrate system performance using sub-resolution fluorescent beads and applied to a test sample consisting of human bone osteosarcoma epithelial cells, with plasma membrane transporter 1 (MCT1) tagged with an enhanced green fluorescent protein (EGFP) at the N-terminal.Ana I. Gomez Varela wishes to acknowledge support from the Xunta de Galicia, Conselleria de Cultura, Educacion e Ordenacion Universitaria e da Conselleria de Economia, Emprego e Industria (Programa de axudas de apoio a etapa de formacion posdoutoral 2017). Adelaide Miranda and Pieter De Beule acknowledge financial support from Norte's Regional Operational Programme 2014-2020-Norte2020 (NORTE-01-0145-FEDER-000019). Sandra Paiva and Rosana Alves thank Fulbright Commission Portugal and Luso-American Development Foundation (FLAD) for their financial support to perform research work at UC Berkeley, California, USA. We thank the U.S. Embassy in Portugal for supporting David Drubin's visit to Portugal. We thank Ann Fisher of the UC Berkeley Cell Culture Facility for help with cell culture. We thank Dr. Kartoosh Heydari of the Cancer Research Lab Flow Cytometry Core Facility of UC Berkeley. Rosana Alves and Claudia Barata-Antunes are recipients of PhD fellowships from the Portuguese Foundation for Science and Technology (PD/BD/113813/2015 and PD/BD/135208/2017, respectively). The authors want to thank Nikon and Izasa Scientific for their support to the experiment by providing a N SIM-E microscope set-up on loan. We also gratefully acknowledge Dr. Kees van der Oord from Nikon Instruments Europe B.V. for his assistance with the SIM microscope as well as Paulo Madureira and Carlos Pitaes from IZASA Portugal and Jordi Recasens from IZASA Spain for their assistance with the integration of the SIM and AFM microscopes. Finally, we want to thank Benjamin Holmes for fruitful discussions and relentless support

Good Random Matrices over Finite Fields

The random matrix uniformly distributed over the set of all m-by-n matrices over a finite field plays an important role in many branches of information theory. In this paper a generalization of this random matrix, called k-good random matrices, is studied. It is shown that a k-good random m-by-n matrix with a distribution of minimum support size is uniformly distributed over a maximum-rank-distance (MRD) code of minimum rank distance min{m,n}-k+1, and vice versa. Further examples of k-good random matrices are derived from homogeneous weights on matrix modules. Several applications of k-good random matrices are given, establishing links with some well-known combinatorial problems. Finally, the related combinatorial concept of a k-dense set of m-by-n matrices is studied, identifying such sets as blocking sets with respect to (m-k)-dimensional flats in a certain m-by-n matrix geometry and determining their minimum size in special cases.Comment: 25 pages, publishe

Micro-CT-scanning as a valuable source of data for musculoskeletal studies in biology

Over time, so-called classic biological studies (such as anatomical studies) have evolved into modern, highly integrated strategies tackling important questions in evolutionary biology. Where early morphologists limited themselves to descriptions based on dissections, non-invasive imaging techniques nowadays allow to uncover details of anatomy in a way that morphologists can go far beyond basic and descriptive anatomy, e.g. through modelling. In this presentation, an overview is presented on some on-going research projects that rely on X-ray tomography data, which focus on the adaptive evolution of musculoskeletal systems in different vertebrate lineages. Cases discussed are (1) a study on the cranial anatomical diversity and functional implications in the feeding apparatus in seahorses, (2) as well as multi-body modelling of the tail system in these fishes; and (3) structural diversity in Darwin’s finches in relation to high performance seed cracking. These cases clearly show the (still not fully explored) potential for testing specific hypotheses with respect to adaptive evolution, where X-ray tomography provides the tools to model experimental conditions that are impossible to achieve with live specimens (e.g. perfect control of specific parameters)

Foreign Direct Investment by Emerging Economy Multinationals: Coping with the Global Crisis

Even before the onset of the global crisis, the global market for foreign direct investment (FDI) had undergone significant changes. Foremost amongst these changes was the increasing importance of emerging market multinationals (MNEs). While outward foreign direct investment (OFDI) from these markets is, in itself, not new, the magnitude that this phenomenon achieved prior to the crisis and its resilience in the face of the global crisis suggest that this is not a temporary occurrence but rather a sign of a fundamental change that is taking place in the global OFDI market. However, emerging markets are not homogenous: in addition to the rise in OFDI from emerging markets, the formation of new regional groupings has led to the emergence of fresh investment patterns. This chapter examines changes taking place in global FDI flows and looks at the impact of the crisis in the context of profound structural changes; it also focuses on the response of emerging markets and the enormous risks and challenges that lie ahead. It is vital to note that this crisis is ongoing, and it is too early to predict the final contours it will leave in its wake on the FDI landscape

Biomarker discovery and redundancy reduction towards classification using a multi-factorial MALDI-TOF MS T2DM mouse model dataset

Diabetes like many diseases and biological processes is not mono-causal. On the one hand multifactorial studies with complex experimental design are required for its comprehensive analysis. On the other hand, the data from these studies often include a substantial amount of redundancy such as proteins that are typically represented by a multitude of peptides. Coping simultaneously with both complexities (experimental and technological) makes data analysis a challenge for Bioinformatics

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma

Background: Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment. Methods: We analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models. Results: Tasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+ cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo. Conclusion: Our study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients

a dynamic model of firms strategic location choice

This paper analyzes the optimal location choice of a firm in a dynamic Cournot framework, in which firms' absorptive capacities may depend on their knowledge stock. The firm decides whether to locate irreversibly in a cluster or in isolation. In the cluster the firm benefits from inward spillovers from its competitors, but also generates outward spillovers. If the firm chooses to locate in isolation no knowledge flows occur. All firms' production costs are determined by their knowledge stocks, which evolve over time due to own R&D investments and potentially inward spillovers. It is shown that, if absorptive capacity is constant, the incentive to locate in the cluster decreases with respect to the firm's knowledge stock. Conversely, if absorptive capacity depends positively on knowledge stock, the firm's incentive to join the cluster is larger the more knowledge it has. It is also shown that qualitative properties of the equilibrium paths of R&D investments and knowledge stocks differ substantially depending on whether absorptive capacities are constant or knowledge dependent

Dust Devil Sediment Transport: From Lab to Field to Global Impact

The impact of dust aerosols on the climate and environment of Earth and Mars is complex and forms a major area of research. A difficulty arises in estimating the contribution of small-scale dust devils to the total dust aerosol. This difficulty is due to uncertainties in the amount of dust lifted by individual dust devils, the frequency of dust devil occurrence, and the lack of statistical generality of individual experiments and observations. In this paper, we review results of observational, laboratory, and modeling studies and provide an overview of dust devil dust transport on various spatio-temporal scales as obtained with the different research approaches. Methods used for the investigation of dust devils on Earth and Mars vary. For example, while the use of imagery for the investigation of dust devil occurrence frequency is common practice for Mars, this is less so the case for Earth. Modeling approaches for Earth and Mars are similar in that they are based on the same underlying theory, but they are applied in different ways. Insights into the benefits and limitations of each approach suggest potential future research focuses, which can further reduce the uncertainty associated with dust devil dust entrainment. The potential impacts of dust devils on the climates of Earth and Mars are discussed on the basis of the presented research results

Inward and Outward FDI Country Profiles, Second Edition

This second edition contains a series of 77 standardized country profiles dealing with the inward and outward foreign direct investment (FDI) performance of 40 economies. The profiles have been peer-reviewed by a global network of experts. The publication is intended to contribute to the analysis of trends in foreign direct investment and policy issues related to them. More specifically, the individual profiles discuss FDI trends and developments (country-level developments, the corporate players); effects of the recent global crises; and the policy scene. Each profile contains a standard set of tables, including on FDI stocks and flows, sectoral and geographical FDI distributions, the largest M&As and greenfield investments, the principal foreign affiliates (for inward FDI), and the principal multinational enterprises (for outward FDI). The standardized template used to produce the profiles allows cross-country comparisons. The volume is meant to be a reference tool for anyone interested in foreign direct investment