Rigid body motion in viscous flows using the Finite Element Method

A new model for the numerical simulation of a rigid body moving in a viscous fluid flow using FEM is presented. One of the most interesting features of this approach is the small computational effort required to solve the motion of the rigid body, comparable to a pure fluid solver. The model is based on the idea of extending the fluid velocity inside the rigid body and solving the flow equations with a penalization term to enforce rigid motion inside the solid. In order to get the velocity field in the fluid domain the Navier-Stokes equations for an incompressible viscous flow are solved using a fractional-step procedure combined with the two-step Taylor-Galerkin for the fractional linear momentum. Once the velocity field in the fluid domain is computed, calculation of the rigid motion is obtained by averaging translation and angular velocities over the solid. One of the main challenges when dealing with the fluid-solid interaction is the proper modelling of the interface which separates the solid moving mass from the viscous fluid. In this work the combination of the level set technique and the two-step Taylor-Galerkin algorithm for tracking the fluid-solid interface is proposed. The good properties exhibited by the two-step Taylor-Galerkin, minimizing oscillations and numerical diffusion, make this method suitable to accurately advect the solid domain avoiding distortions at its boundaries, and thus preserving the initial size and shape of the rigid body. The proposed model has been validated against empirical solutions, experimental data and numerical simulations found in the literature. In all tested cases, the numerical results have shown to be accurate, proving the potential of the proposed model as a valuable tool for the numerical analysis of the fluid-solid interaction.Comment: Research article; 41 pages, 40 figures, 5 tables, 91 reference

Validation of a gas chromatography-mass spectrometry method for the analysis of sterol oxidation products in serum

A validated gas chromatography-mass spectrometry (GC-MS) detection method for the quantitative analysis of sterol oxidation products (SOPs) in serum is described. After a lipid extraction procedure with chloroform-methanol, a cold saponification and purification by solid phase extraction, oxysterols were derivatized to form trimethyl-sylil-ethers which were subjected to GC-MS analysis. Calibration curves for cholesterol oxidation products showed determination coefficient (R(2)) of 1.0, with low values for the coefficient of variation of the response factors (< 1%). Detection and quantification limits were below 5 ng/mL and 10 ng/mL, respectively. Recovery data were between 77.65% and 110.29% (CV < 10% for all compounds). Good results were obtained for within- and between-day repeatability, with values below 10%. In conclusion, the method performed is suitable for the determination and quantification of SOPs in serum

Boulder exhumation and segregation by impacts on rubble-pile asteroids

Small asteroids are often considered to be rubble-pile objects, and such asteroids may be the most likely type of Near Earth Objects (NEOs) to pose a threat to Earth. However, impact cratering on such bodies is complex and not yet understood. We perform three low-velocity (≈ 400 m/s) impact experiments in granular targets with and without projectile-size boulders. We conducted SPH simulations that closely reproduced the impact experiments. Our results suggest that cratering on heterogeneous targets displaces and ejects boulders, rather than fragmenting them, unless directly hit. We also see indications that as long as the energy required to disrupt the boulder is small compared to the kinetic energy of the impact, the disruption of boulders directly hit by the projectile may have minimal effect on the crater size. The presence of boulders within the target causes ejecta curtains with higher ejection angles compared to homogeneous targets. At the same time, there is a segregation of the fine ejecta from the boulders, resulting in boulders landing at larger distances than the surrounding fine grained material. However, boulders located in the target near the maximum extent of the expanding excavation cavity are merely exhumed and distributed radially around the crater rim, forming ring patterns similar to the ones observed on asteroids Itokawa, Ryugu and Bennu. Altogether, on rubble-pile asteroids this process will redistribute boulders and finer-grained material heterogeneously, both areally around the crater and vertically in the regolith. In the context of a kinetic impactor on a rubble-pile asteroid and the DART mission, our results indicate that the presence of boulders will reduce the momentum transfer compared to a homogeneous, fine-grained target

The perceptual shaping of anticipatory actions

Humans display anticipatory motor responses to minimize the adverse effects of predictable perturbations. A widely accepted explanation for this behaviour relies on the notion of an inverse model that, learning from motor errors, anticipates corrective responses. Here, we propose and validate the alternative hypothesis that anticipatory control can be realized through a cascade of purely sensory predictions that drive the motor system, reflecting the causal sequence of the perceptual events preceding the error. We compare both hypotheses in a simulated anticipatory postural adjustment task. We observe that adaptation in the sensory domain, but not in the motor one, supports the robust and generalizable anticipatory control characteristic of biological systems. Our proposal unites the neurobiology of the cerebellum with the theory of active inference and provides a concrete implementation of its core tenets with great relevance both to our understanding of biological control systems and, possibly, to their emulation in complex artefacts

Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening

Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS: In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS: The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS: Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy groupSupported by grants from Asociación Española contra el Cáncer (Fundación Científica and Junta de Barcelona), Instituto de Salud Carlos III (PI08/90717), FEDER funds, and Agència de Gestió d’Ajuts Universitaris i de Recerca (2009SGR849). Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) is funded by Instituto de Salud Carlos III. In the Basque Country, the study received additional grants from Obra Social de Kutxa, Diputación Foral de Gipuzkoa (DFG 07/5), Departamento de Sanidad del Gobierno Vasco, EITB-Maratoia (BIO 07/ CA/19), and Acción Transversal contra el Cáncer del CIBERehd (2008). In Galicia, this work was supported by Dirección Xeral de Innovación e Xestión da Saúde Pública, Conselleria de Sanidade, and Xunta de Galicia. Eiken Chemical of Japan and its Spanish representatives, Palex Medical and Biogen Diagnóstica, donated supplies and automated analyzers used for FI

Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe

Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis

Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted

A high throughput screen for next-generation leads targeting malaria parasite transmission

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel

(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3-0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4-0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2-0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1-3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1-2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2-2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2-1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1-3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX

Herschel FIR counterparts of selected Ly-alpha emitters at z~2.2. Fast evolution since z~3 or missed obscured AGNs?

Ly-alpha emitters (LAEs) are seen everywhere in the redshift domain from local to z~7. Far-infrared (FIR) counterparts of LAEs at different epochs could provide direct clues on dust content, extinction, and spectral energy distribution (SED) for these galaxies. We search for FIR counterparts of LAEs that are optically detected in the GOODS-North field at redshift z~2.2 using data from the Herschel Space Telescope with the Photodetector Array Camera and Spectrometer (PACS). The LAE candidates were isolated via color-magnitude diagram using the medium-band photometry from the ALHAMBRA Survey, ancillary data on GOODS-North, and stellar population models. According to the fitting of these spectral synthesis models and FIR/optical diagnostics, most of them seem to be obscured galaxies whose spectra are AGN-dominated. From the analysis of the optical data, we have observed a fraction of AGN or composite over source total number of ~0.75 in the LAE population at z~2.2, which is marginally consistent with the fraction previously observed at z=2.25 and even at low redshift (0.2<z<0.45), but significantly different from the one observed at redshift ~3, which could be compatible either with a scenario of rapid change in the AGN fraction between the epochs involved or with a non detection of obscured AGN in other z=2-3 LAE samples due to lack of deep FIR observations. We found three robust FIR (PACS) counterparts at z~2.2 in GOODS-North. This demonstrates the possibility of finding dust emission in LAEs even at higher redshifts.Comment: 11 pages (including Appendices), 6 figures. Accepted for publication in Astronomy & Astrophysics Letters (two references added