An efficient adaptive multigrid algorithm for predicting thin film flow on surfaces containing localised topographic features

Gravity-driven continuous thin film flow over a plane, containing well-defined single and grouped topographic features, is modelled as a Stokes flow using lubrication theory. The associated time dependent, nonlinear, coupled set of governing equations are solved using a Full Approximation Storage (FAS) Multigrid algorithm by employing automatic mesh adaptivity, the power efficiency and accuracy of which is demonstrated by comparing the results with corresponding global fine-mesh solutions.. These show that automatic grid refinement effectively restricts the use of find grids to regions of rapid flow development which, for flow over the topographies considered, includes the topography itself, the upstream Capillary ridge, downstream sure region, and the characteristic bow wave. It is shown that for the accurate solution of such flow problems, adaptive Multigridding offers increased flexibility together with a significant reduction in memory requirement. This is further demonstrated by solving the problem of transient flow over a trench topography, generated by a sinusoidally varying inlet condition

Feline mammary carcinoma stem cells are tumorigenic, radioresistant, chemoresistant and defective in activation of the ATM/p53 DNA damage pathway

AbstractCancer stem cells were identified in a feline mammary carcinoma cell line by demonstrating expression of CD133 and utilising the tumour sphere assay. A population of cells was identified that had an invasive, mesenchymal phenotype, expressed markers of pluripotency and enhanced tumour formation in the NOD-SCID mouse and chick embryo models. This population of feline mammary carcinoma stem cells was resistant to chemotherapy and radiation, possibly due to aberrant activation of the ATM/p53 DNA damage pathway. Epithelial–mesenchymal transition was a feature of the invasive phenotype. These data demonstrate that cancer stem cells are a feature of mammary cancer in cats

Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic outgrowth in bone

The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state in which cancer cells persist prior to overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling in the retention of cancer cell dormancy. We demonstrate that loss of tumor-intrinsic type I IFN occurs in proliferating prostate cancer cells in bone. This loss suppresses tumor immunogenicity and therapeutic response and promotes bone cell activation to drive cancer progression. Restoration of tumor-intrinsic IFN signaling by HDAC inhibition increased tumor cell visibility, promoted long-term antitumor immunity, and blocked cancer growth in bone. Key findings were validated in patients, including loss of tumor-intrinsic IFN signaling and immunogenicity in bone metastases compared to primary tumors. Data herein provide a rationale as to why current immunotherapeutics fail in bone-metastatic prostate cancer, and provide a new therapeutic strategy to overcome the inefficacy of immune-based therapies in solid cancers.Katie L Owen, Linden J Gearing, Damien J Zanker, Natasha K Brockwell, Weng Hua Khoo, Daniel L Roden, Marek Cmero, Stefano Mangiola, Matthew K Hong, Alex J Spurling, Michelle McDonald, Chia-Ling Chan, Anupama Pasam, Ruth J Lyons, Hendrika M Duivenvoorden, Andrew Ryan, Lisa M Butler, John M Mariadason, Tri Giang Phan, Vanessa M Hayes, Shahneen Sandhu, Alexander Swarbrick, Niall M Corcoran, Paul J Hertzog, Peter I Croucher, Chris Hovens, Belinda S Parke

Moderators of Exercise Effects on Cancer-related Fatigue:A Meta-analysis of Individual Patient Data

PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue. METHODS: We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test. RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (β = -0.17; 95% confidence interval [CI], -0.22 to -0.12). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (βdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (β = -0.29; 95% CI, -0.39 to -0.20) than supervised interventions with a longer duration. CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration

Sub-shell closure and shape coexistence in the transitional nucleus Zr 98

In the rapid shape change from spherical to deformed nuclei in the Z=40 Zr isotopic chain, recent work has identified shape coexistence in Zr96. Between Zr96 and the strongly deformed Zr100, Zr98 is expected to also exhibit coexistence of nuclear shapes. The degree of mixing between different configurations is mainly determined by the nucleon-nucleon interactions. For nuclear model predictions, experimental constraints are needed, but they are barely available for Zr98. To study low-lying transitions in Zr98, a Coulomb excitation experiment was conducted at the Argonne Tandem-Linac Accelerator System (ATLAS) facility using a Zr98 beam extracted from the Californium Rare Ion Breeder Upgrade (CARIBU) ion source and Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) for γ-ray spectroscopy coupled to the compact heavy ion counter (CHICO2) for ion detection. This paper reports on the first decisive deduction of the B(E2;21+→01+) transition strength in Zr98 and on its interpretation

First direct observation of enhanced octupole collectivity in 146Ba

The octupole strength present in the neutron-rich, radiocative nucleus 146Ba has been experimentally determined for the first time using Coulomb excitation. To achieve this, A=146 fission fragments from CARIBU were post-accelerated by the Argonne Tandem Linac Accelerator System (ATLAS) and impinged on a thin 208Pb target. Using the GRETINA γ-ray spectrometer and the CHICO2 heavy-ion counter, the reduced transition probability B(E3; 3-→0+) was determined as 48(+21-29) W.u. The new result provides further experimental evidence for the presence of a region of octupole deformation surrounding the neutron-rich barium isotopes

Shape coexistence and the role of axial asymmetry in 72Ge

The quadrupole collectivity of low-lying states and the anomalous behavior of the 02+ and 23+ levels in 72Ge are investigated via projectile multi-step Coulomb excitation with GRETINA and CHICO-2. A total of forty six E2 and M1 matrix elements connecting fourteen low-lying levels were determined using the least-squares search code, gosia. Evidence for triaxiality and shape coexistence, based on the model-independent shape invariants deduced from the Kumar-Cline sum rule, is presented. These are interpreted using a simple two-state mixing model as well as multi-state mixing calculations carried out within the framework of the triaxial rotor model. The results represent a significant milestone towards the understanding of the unusual structure of this nucleus