68 research outputs found

    Multi-time-lag PIV analysis of steady and pulsatile flows in a sidewall aneurysm

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    The effect of inflow waveform on the hemodynamics of a real-size idealized sidewall intracranial aneurysm (IA) model was investigated using particle imaging velocimetry (PIV). For this purpose, we implemented an error analysis based on several PIV measurements with different time lags to ensure high precision of velocity fields measured in both the IA and the parent artery. The relative error measured in the main part of the circulating volume was <1% despite the three orders of magnitude difference of parent artery and IA dome velocities. Moreover, important features involved in IA evolution were potentially emphasized from the qualitative and quantitative flow pattern comparison resulting from steady and unsteady inflows. In particular, the flow transfer in IA and the vortical structure were significantly modified when increasing the number of harmonics for a typical physiological flow, in comparison with quasi-steady conditions

    Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.

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    The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy

    No silver bullet for digital soil mapping: country-specific soil organic carbon estimates across Latin America.

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    Country-specific soil organic carbon (SOC) estimates are the baseline for the Global SOC Map of the Global Soil Partnership (GSOCmap-GSP). This endeavor is key to explaining the uncertainty of global SOC estimates but requires harmonizing heterogeneous datasets and building country-specific capacities for digital soil mapping (DSM).We identified country-specific predictors for SOC and tested the performance of five predictive algorithms for mapping SOC across Latin America. The algorithms included support vector machines (SVMs), random forest (RF), kernel-weighted nearest neighbors (KK), partial least squares regression (PL), and regression kriging based on stepwise multiple linear models (RK). Country-specific training data and SOC predictors (5 x 5 km pixel resolution) were obtained from ISRIC - World Soil Information. Temperature, soil type, vegetation indices, and topographic constraints were the best predictors for SOC, but country-specific predictors and their respective weights varied across Latin America. We compared a large diversity of country-specific datasets and models, and were able to explain SOC variability in a range between ~ 1 and ~ 60 %, with no universal predictive algorithm among countries. A regional (n = 11 268 SOC estimates) ensemble of these five algorithms was able to explain ~ 39% of SOC variability from repeated 5-fold cross-validation.We report a combined SOC stock of 77.8 +- 43.6 Pg (uncertainty represented by the full conditional response of independent model residuals) across Latin America. SOC stocks were higher in tropical forests (30 +- 16.5 Pg) and croplands (13 +- 8.1 Pg). Country-specific and regional ensembles revealed spatial discrepancies across geopolitical borders, higher elevations, and coastal plains, but provided similar regional stocks (77.8 +- 42.2 and 76.8 +- 45.1 Pg, respectively). These results are conservative compared to global estimates (e.g., SoilGrids250m 185.8 Pg, the Harmonized World Soil Database 138.4 Pg, or the GSOCmap-GSP 99.7 Pg). Countries with large area (i.e., Brazil, Bolivia, Mexico, Peru) and large spatial SOC heterogeneity had lower SOC stocks per unit area and larger uncertainty in their predictions. We highlight that expert opinion is needed to set boundary prediction limits to avoid unrealistically high modeling estimates. For maximizing explained variance while minimizing prediction bias, the selection of predictive algorithms for SOC mapping should consider density of available data and variability of country-specific environmental gradients. This study highlights the large degree of spatial uncertainty in SOC estimates across Latin America. We provide a framework for improving country-specific mapping efforts and reducing current discrepancy of global, regional, and country-specific SOC estimates

    Sensitivity of Global Translation to mTOR Inhibition in REN Cells Depends on the Equilibrium between eIF4E and 4E-BP1

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    Initiation is the rate-limiting phase of protein synthesis, controlled by signaling pathways regulating the phosphorylation of translation factors. Initiation has three steps, 43S, 48S and 80S formation. 43S formation is repressed by eIF2α phosphorylation. The subsequent steps, 48S and 80S formation are enabled by growth factors. 48S relies on eIF4E-mediated assembly of eIF4F complex; 4E-BPs competitively displace eIF4E from eIF4F. Two pathways control eIF4F: 1) mTORc1 phosphorylates and inactivates 4E-BPs, leading to eIF4F formation; 2) the Ras-Mnk cascade phosphorylates eIF4E. We show that REN and NCI-H28 mesothelioma cells have constitutive activation of both pathways and maximal translation rate, in the absence of exogenous growth factors. Translation is rapidly abrogated by phosphorylation of eIF2α. Surprisingly, pharmacological inhibition of mTORc1 leads to the complete dephosphorylation of downstream targets, without changes in methionine incorporation. In addition, the combined administration of mTORc1 and MAPK/Mnk inhibitors has no additive effect. The inhibition of both mTORc1 and mTORc2 does not affect the metabolic rate. In spite of this, mTORc1 inhibition reduces eIF4F complex formation, and depresses translocation of TOP mRNAs on polysomes. Downregulation of eIF4E and overexpression of 4E-BP1 induce rapamycin sensitivity, suggesting that disruption of eIF4F complex, due to eIF4E modulation, competes with its recycling to ribosomes. These data suggest the existence of a dynamic equilibrium in which eIF4F is not essential for all mRNAs and is not displaced from translated mRNAs, before recycling to the next

    Accuracy assessment of CBCT-based volumetric brain shift field

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    The displacement of the brain parenchyma during open brain surgery, known as ‘brain shift’, affects the applicability of pre-operative planning and affects the outcome of the surgery. In this article we investigated the accuracy of a novel method to intra-operatively determine the brain shift displacement field throughout the whole brain volume. The brain shift displacement was determined by acquiring contrast enhanced cone-beam CT before and during the surgery. The respective datasets were pre-processed, landmark enhanced, and elastically registered to find the displacement field. The accuracy of this method was evaluated by artificially creating post-operative data with a known ground truth deformation. The artificial post-operative data was obtained by applying the deformation field from one patient on the pre-operative data of another patient, which was repeated for three patients. The mean error that was found with this method ranged from 1 to 2 mm, while the standard deviation was about 1 mm

    Quality traits of wild and farmed turbot commercialized by an Italian supermarket company

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    The study aimed at comparing quality of the meat of reared turbot, coming from a Spanish farm that supplied an important Italian supermarket company, with that of wild turbots

    Volumetric measurements of brain shift using intraoperative cone-beam computed tomography: preliminary study

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    BACKGROUND: Cerebrospinal fluid leakage and ventricular compression during open surgery may lead to brain deformation called brain shift. Brain shift may affect intraoperative navigation that is based on image-based preoperative planning. Tools to correct or predict these anatomic modifications can be important to maintain precision during open guided neurosurgery. OBJECTIVE: To obtain a reliable intraoperative volumetric deformation vector field describing brain shift during intracranial neurosurgical procedures. METHODS: We acquired preoperative and intraoperative cone-beam computed tomography enhanced with intravenous injection of iodine contrast. These data sets were preprocessed and elastically registered to obtain the volumetric brain shift deformation vector fields. RESULTS: We obtained the brain shift deformation vector field in 9 cases. The deformation fields proved to be highly nonlinear, particularly around the ventricles. Interpatient variability was considerable, with a maximum deformation ranging from 8.1 to 26.6 mm and a standard deviation ranging from 0.9 to 4.9 mm. CONCLUSION: Contrast-enhanced cone-beam computed tomography provides a feasible technique for intraoperatively determining brain shift deformation vector fields. This technique can be used perioperatively to adjust preoperative planning and coregistration during neurosurgical procedures

    Quality traits of wild and farmed turbot commercialized by an Italian supermarket company.

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    The study aim to comparing quality of the meat of reared turbot, coming from a Spanish farm that supplied an important supermarket company, whit that of wild turbots. As regard to chemical composition, he results showed that all the turbots from aquaculture had a very low fat content that may allow to include also farmed turbot in the lean fish group (N. C. R. 2002)
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