Large-eddy simulation of pyroclastic density currents

We investigate the dynamics of turbulent pyroclastic density currents (PDCs) by adopting a 3D, Eulerian-Eulerian multiphase flow model, in which solid particles are treated as a continuum and the grain-size distribution is simplified by assuming two particulate phases. The turbulent sub-grid stress of the gas phase is modelled within the framework of Large-Eddy Simulation (LES) by means of a eddy-viscosity model together with a wall closure. Despite the significant numerical diffusion associated to the upwind method adopted for the Finite-Volume discretization, numerical simulations demonstrate the need of adopting a Sub-Grid Scale (SGS) model, while revealing the complex interplay between the grid and the SGS filter sizes. We also analyse the relationship between the averaged flow dynamic pressure and the action exerted by the PDC on a cubic obstacle, to evaluate the impact of a PDC on a building. Numerical results suggest that the average flow dynamic pressure can be used as a proxy for the force per unit surface acting on the building envelope (Fig. 5), even for such steeply stratified flows. However, it is not possible to express such roportionality as a constant coefficient such as the drag coefficient in a steady-state current. The present results indeed indicate that the large epistemic and aleatory uncertainty on initial and boundary conditions has an impact on the numerical redictions which is comparable to that of grid resolution

Engineered membranes for residual cell trapping on microfluidic blood plasma separation systems. A comparison between porous and nanofibrous membranes

Blood-based clinical diagnostics require challenging limit-of-detection for low abundance, circulating molecules in plasma. Micro-scale blood plasma separation (BPS) has achieved remarka-ble results in terms of plasma yield or purity, but rarely achieving both at the same time. Here, we proposed the first use of electrospun polylactic-acid (PLA) membranes as filters to remove residual cell population from continuous hydrodynamic-BPS devices. The membranes hydrophilicity was improved by adopting a wet chemistry approach via surface aminolysis as demonstrated through Fourier Transform Infrared Spectroscopy and Water Contact Angle analysis. The usability of PLA-membranes was assessed through degradation measurements at extreme pH values. Plasma purity and hemolysis were evaluated on plasma samples with residual red blood cell content (1, 3, 5% hematocrit) corresponding to output from existing hydrodynamic BPS systems. Commercially available membranes for BPS were used as benchmark. Results highlighted that the electrospun membranes are suitable for downstream residual cell removal from blood, permitting the collection of up to 2 mL of pure and low-hemolyzed plasma. Fluorometric DNA quantification revealed that electrospun membranes did not significantly affect the concentration of circulating DNA. PLA-based electrospun membranes can be combined with hydrodynamic BPS in order to achieve high volume plasma separation at over 99% plasma purity

A Short Counterexample Property for Safety and Liveness Verification of Fault-tolerant Distributed Algorithms

Distributed algorithms have many mission-critical applications ranging from embedded systems and replicated databases to cloud computing. Due to asynchronous communication, process faults, or network failures, these algorithms are difficult to design and verify. Many algorithms achieve fault tolerance by using threshold guards that, for instance, ensure that a process waits until it has received an acknowledgment from a majority of its peers. Consequently, domain-specific languages for fault-tolerant distributed systems offer language support for threshold guards. We introduce an automated method for model checking of safety and liveness of threshold-guarded distributed algorithms in systems where the number of processes and the fraction of faulty processes are parameters. Our method is based on a short counterexample property: if a distributed algorithm violates a temporal specification (in a fragment of LTL), then there is a counterexample whose length is bounded and independent of the parameters. We prove this property by (i) characterizing executions depending on the structure of the temporal formula, and (ii) using commutativity of transitions to accelerate and shorten executions. We extended the ByMC toolset (Byzantine Model Checker) with our technique, and verified liveness and safety of 10 prominent fault-tolerant distributed algorithms, most of which were out of reach for existing techniques.Comment: 16 pages, 11 pages appendi

Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer.

Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response

Glucose metabolism enzymes gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer (CRC)

No abstract availabl

Drug holidays and overall survival of patients with metastatic colorectal cancer

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni-and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni-and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22\u20132.32; p = 0.002 and HR,4.89; 95% CI, 3.33\u20137.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer

Clinical and molecular determinants of extrahepatic disease progression (ePD) in initially unresectable, liver-limited metastatic colorectal cancer (mCRC)

e15511Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic o..

Polylactic is a Sustainable, Low Absorption, Low Autofluorescence Alternative to Other Plastics for Microfluidic and Organ-on-Chip Applications

Organ-on-chip (OOC) devices are miniaturized devices replacing animal models in drug discovery and toxicology studies. The majority of OOC devices are made from polydimethylsiloxane (PDMS), an elastomer widely used in microfluidic prototyping, but posing a number of challenges to experimentalists, including leaching of uncured oligomers and uncontrolled absorption of small compounds. Here we assess the suitability of polylactic acid (PLA) as a replacement material to PDMS for microfluidic cell culture and OOC applications. We changed the wettability of PLA substrates and demonstrated the functionalization method to be stable over a time period of at least 9 months. We successfully cultured human cells on PLA substrates and devices, without coating. We demonstrated that PLA does not absorb small molecules, is transparent (92% transparency), and has low autofluorescence. As a proof of concept of its manufacturability, biocompatibility, and transparency, we performed a cell tracking experiment of prostate cancer cells in a PLA device for advanced cell culture