Tumor Lymphangiogenesis as a Potential Therapeutic Target

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis

VtkSMP: Task-based Parallel Operators for VTK Filters

International audienceNUMA nodes are potentially powerful but taking benefit of their capabilities is challenging due to their architec- ture (multiple computing cores, advanced memory hierarchy). They are nonetheless one of the key components to enable processing the ever growing amount of data produced by scientific simulations. In this paper we study the parallelization of patterns commonly used in VTK algorithms and propose a new multi- threaded plugin for VTK that eases the development of parallel multi-core VTK filters. We specifically focus on task-based approaches and show that with a limited code refactoring effort we can take advantage of NUMA node capabilities. We experiment our patterns on a transform filter, base isosurface extraction filter and a min/max tree accelerated isosurface extraction. We support 3 programming environments, OpenMP, Intel TBB and X-KAAPI, and propose different algorithmic refinements according to the capabilities of the target environment. Results show that we can speed execution up to 30 times on a 48-core machine

The realities of storing carbon dioxide - A response to CO2 storage capacity issues raised by Ehlig-Economides & Economides

In a recent publication, Ehlig-Economides & Economides (2010) have sought to demonstrate that carbon dioxide capture and storage (CCS) is not technically or economically feasible, based on a supposed lack of underground storage capacity. We consider this to be a serious misrepresentation of the scientific, engineering and operational facts surrounding CCS. Ehlig-Economides & Economides raise a number of storage related issues: reservoir boundaries, capacity, pressure management, storage integrity, dissolution and storage in depleted reservoirs. We take each one in turn, highlighting specific errors in the paper but also drawing attention to more general background issues. Finally, we discuss in more detail some inconsistencies in the paper surrounding the reservoir engineering calculations

Proposal for an integrated silicon-photonics terahertz gas detector using photoacoustics

A design and multiphysical model is presented for an on-chip gas sensor that transduces terahertz gas absorption through sound generation into a mechanical motion that can be read out externally. The signal is triply enhanced by designing a structure that functions simultaneously as an optical, an acoustical and a mechanical resonator. The structure is made in high-resistivity silicon and can be fabricated using CMOS and HEMS fabrication technologies. The sensor is a purely passive element, so an external THz source and read-out are required. The chip has a footprint of 3 mm(2). A detection limit of 234 ppb of methanol for a source power of 1 mW and an integration time of 1 ms is predicted. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria

Background: In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. Methods: A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Results: Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. Conclusions: The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria

Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria

Background: In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. Methods: A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Results: Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. Conclusions: The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria

Prevalence of viral and non-viral hepatitis in Menoua Division, West Region, Cameroon: a retrospective hospital-based study

Introduction: the paucity of data on hepatitis' epidemiology in Menoua Division, west region, Cameroon, prompted us to assess the prevalence of viral and non-viral hepatitis in this area. Methods: a retrospective exhaustive study based on records of patients from January 2008 to June 2014 was conducted in 9 health centres in Menoua Division. Targeted subjects were patients who did not receive hepatitis vaccines for the past year and have been screened for hepatitis B virus (HBV), hepatitis C virus (HCV) and/or a blood transaminase. Associations between variables were quantified with odd ratios (OR) and 95% confidence interval (CI). Cochran-Armitage test of linear trend was used for testing proportions of ordinal variables. Fisher's exact test was used for testing the association between 2 qualitative variables when expected counts were less than 5. Results: the overall prevalence were 9.6% and 6.7% for HBV and HCV respectively. HBV mostly infected people aged 21-30 (12.4%) while the prevalence of HCV increased with age up to 35.4% (p=0.03). A 0.6% co-infection was observed. Thirty percent of positive HBV or HCV had high transaminase while 13% of patients with elevated transaminase showed negative viral serology. Conclusion: these results show that hospital-based prevalence of HCV and HBV in Menoua Division is under the Cameroon's national range but point out the fact that non-viral hepatitis might be a serious case of concern in this area. There is therefore, a need to identify the risk-factors of non-viral hepatitis

Calibration of TCCON column-averaged CO2: the first aircraft campaign over European TCCON sites

The Total Carbon Column Observing Network (TCCON) is a ground-based network of Fourier Transform Spectrometer (FTS) sites around the globe, where the column abundances of CO2, CH4, N2O, CO and O2 are measured. CO2 is constrained with a precision better than 0.25% (1-σ). To achieve a similarly high accuracy, calibration to World Meteorological Organization (WMO) standards is required. This paper introduces the first aircraft calibration campaign of five European TCCON sites and a mobile FTS instrument. A series of WMO standards in-situ profiles were obtained over European TCCON sites via aircraft and compared with retrievals of CO2 column amounts from the TCCON instruments. The results of the campaign show that the FTS measurements are consistently biased 1.1% ± 0.2% low with respect to WMO standards, in agreement with previous TCCON calibration campaigns. The standard a priori profile for the TCCON FTS retrievals is shown to not add a bias. The same calibration factor is generated using aircraft profiles as a priori and with the TCCON standard a priori. With a calibration to WMO standards, the highly precise TCCON CO2 measurements of total column concentrations provide a suitable database for the calibration and validation of nadir-viewing satellite