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

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

Molecular systematics of the genus Artibeus (Chiroptera

a b s t r a c t A molecular phylogeny of the genus Artibeus using 19 of the 20 recognized species, many with samples from a broad geographic range, is presented. The analysis shows a clear distinction between the two subgenera (or genera), the &apos;large&apos; Artibeus and the &apos;small&apos; Dermanura, in both mitochondrial and nuclear genes. The placement and status of A. concolor remains inconclusive and is presented as the third subgenus Koopmania. The phylogenies and divergence time estimates show a marked influence of the Andes in the formation of the subgenera and the main lineages inside each subgenus. Nuclear genes showed a highly incomplete lineage sorting among species inside subgenera Artibeus and Dermanura. Indeed, shared alleles were also found between Artibeus and Koopmania, which are presumed to have split apart during the Miocene, showing that great care should be taken in using these markers. Cytochrome-b gene divergences and monophyly analyses suggest that A. lituratus and A. intermedius are indeed conspecifics. These analyses also suggested the existence of at least four &apos;new&apos; species revealing a significant cryptic diversity inside the genus

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

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

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

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

Detection of hexavalent uranium with inline and field-portable immunosensors

An antibody that recognizes a chelated form of hexavalent uranium was used in the development of two different immunosensors for uranium detection. Specifically, these sensors were utilized for the analysis of groundwater samples collected during a 2007 field study of in situ bioremediation in a aquifer located at Rifle, CO. The antibody-based sensors provided data comparable to that obtained using Kinetic Phosphorescence Analysis (KPA). Thus, these novel instruments and associated reagents should provide field researchers and resource managers with valuable new tools for on-site data acquisition

HER3 Is an Actionable Target in Advanced Prostate Cancer.

It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that membranous HER3 protein is commonly highly expressed in lethal prostate cancer, associating with reduced time to castration resistance (CR) and survival. Multiplex immunofluorescence indicated that the HER3 ligand NRG1 is detectable primarily in tumor-infiltrating myelomonocytic cells in human prostate cancer; this observation was confirmed using single-cell RNA sequencing of human prostate cancer biopsies and murine transgenic prostate cancer models. In castration-resistant prostate cancer (CRPC) patient-derived xenograft organoids with high HER3 expression as well as mouse prostate cancer organoids, recombinant NRG1 enhanced proliferation and survival. Supernatant from murine bone marrow-derived macrophages and myeloid-derived suppressor cells promoted murine prostate cancer organoid growth in vitro, which could be reversed by a neutralizing anti-NRG1 antibody and ERBB inhibition. Targeting HER3, especially with the HER3-directed antibody-drug conjugate U3-1402, exhibited antitumor activity against HER3-expressing prostate cancer. Overall, these data indicate that HER3 is commonly overexpressed in lethal prostate cancer and can be activated by NRG1 secreted by myelomonocytic cells in the tumor microenvironment, supporting HER3-targeted therapeutic strategies for treating HER3-expressing advanced CRPC. SIGNIFICANCE: HER3 is an actionable target in prostate cancer, especially with anti-HER3 immunoconjugates, and targeting HER3 warrants clinical evaluation in prospective trials

The sacral chordoma margin

[Objective]: Aim of the manuscript is to discuss how to improve margins in sacral chordoma. [Background]: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery. [Methods]: A multidisciplinary meeting of the “Chordoma Global Consensus Group” was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed. [Results]: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment. [Conclusion]: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients

Characterization of Archaeal Community in Contaminated and Uncontaminated Surface Stream Sediments

Archaeal communities from mercury and uranium-contaminated freshwater stream sediments were characterized and compared to archaeal communities present in an uncontaminated stream located in the vicinity of Oak Ridge, TN, USA. The distribution of the Archaea was determined by pyrosequencing analysis of the V4 region of 16S rRNA amplified from 12 streambed surface sediments. Crenarchaeota comprised 76% of the 1,670 archaeal sequences and the remaining 24% were from Euryarchaeota. Phylogenetic analysis further classified the Crenarchaeota as a Freshwater Group, Miscellaneous Crenarchaeota group, Group I3, Rice Cluster VI and IV, Marine Group I and Marine Benthic Group B; and the Euryarchaeota into Methanomicrobiales, Methanosarcinales, Methanobacteriales, Rice Cluster III, Marine Benthic Group D, Deep Sea Hydrothermal Vent Euryarchaeota 1 and Eury 5. All groups were previously described. Both hydrogen- and acetate-dependent methanogens were found in all samples. Most of the groups (with 60% of the sequences) described in this study were not similar to any cultivated isolates, making it difficult to discern their function in the freshwater microbial community. A significant decrease in the number of sequences, as well as in the diversity of archaeal communities was found in the contaminated sites. The Marine Group I, including the ammonia oxidizer Nitrosopumilus maritimus, was the dominant group in both mercury and uranium/nitrate-contaminated sites. The uranium-contaminated site also contained a high concentration of nitrate, thus Marine Group I may play a role in nitrogen cycle