CFD Simulation of Near-Field Pollutant Dispersion on a High-Resolution Grid: A Case Study by LES and RANS for a Building Group in Downtown Montreal

Turbulence modeling and validation by experiments are key issues in the simulation of micro-scale atmospheric dispersion. This study evaluates the performance of two different modeling approaches (RANS standard k-ε and LES) applied to pollutant dispersion in an actual urban environment: downtown Montreal. The focus of the study is on near-field dispersion, i.e. both on the prediction of pollutant concentrations in the surrounding streets (for pedestrian outdoor air quality) and on building surfaces (for ventilation system inlets and indoor air quality). The high-resolution CFD simulations are performed for neutral atmospheric conditions and are validated by detailed wind-tunnel experiments. A suitable resolution of the computational grid is determined by grid-sensitivity analysis. It is shown that the performance of the standard k-ε model strongly depends on the turbulent Schmidt number, whose optimum value is case-dependent and a priori unknown. In contrast, LES with the dynamic subgrid-scale model shows a better performance without requiring any parameter input to solve the dispersion equation

On Convergence of the Inexact Rayleigh Quotient Iteration with the Lanczos Method Used for Solving Linear Systems

For the Hermitian inexact Rayleigh quotient iteration (RQI), the author has established new local general convergence results, independent of iterative solvers for inner linear systems. The theory shows that the method locally converges quadratically under a new condition, called the uniform positiveness condition. In this paper we first consider the local convergence of the inexact RQI with the unpreconditioned Lanczos method for the linear systems. Some attractive properties are derived for the residuals, whose norms are $\xi_{k+1}$'s, of the linear systems obtained by the Lanczos method. Based on them and the new general convergence results, we make a refined analysis and establish new local convergence results. It is proved that the inexact RQI with Lanczos converges quadratically provided that $\xi_{k+1}\leq\xi$ with a constant $\xi\geq 1$. The method is guaranteed to converge linearly provided that $\xi_{k+1}$ is bounded by a small multiple of the reciprocal of the residual norm $\|r_k\|$ of the current approximate eigenpair. The results are fundamentally different from the existing convergence results that always require $\xi_{k+1}<1$, and they have a strong impact on effective implementations of the method. We extend the new theory to the inexact RQI with a tuned preconditioned Lanczos for the linear systems. Based on the new theory, we can design practical criteria to control $\xi_{k+1}$ to achieve quadratic convergence and implement the method more effectively than ever before. Numerical experiments confirm our theory.Comment: 20 pages, 8 figures. arXiv admin note: text overlap with arXiv:0906.223

Current Indications of Secondary Enucleation in Retinoblastoma Management: A Position Paper on Behalf of the European Retinoblastoma Group (EURbG).

Secondary enucleation (SE) puts an irreversible end to eye-preserving therapies, whenever their prolongation is expected to violate the presumed state of metastatic grace. At present, it must be acknowledged that clear criteria for SE are missing, leading to empiric and subjective indications commonly related to disease progression or relapse, disease persistence masking the optic nerve head or treatment-related complications obscuring the fundus view. This absence of evidence-based consensus regarding SE is explained by the continuously moving frontiers of the conservative management as a result of diagnostic and therapeutic advances, as well as by the lack of studies sufficiently powered to accurately stratify the risk of metastasis in conservatively treated patients. In this position paper of the European Retinoblastoma Group (EURbG), we give an overview of the progressive shift in the indications for SE over the past decades and propose guidelines to assist decision-making with respect to when SE becomes imperative or recommended, with corresponding absolute and relative SE indications. Further studies and validation of biologic markers correlated with the risk of metastasis are expected to set more precisely the frontiers of conservative management and thus consensual criteria for SE in the future

Lateral Gene Expression in Drosophila Early Embryos Is Supported by Grainyhead-Mediated Activation and Tiers of Dorsally-Localized Repression

The general consensus in the field is that limiting amounts of the transcription factor Dorsal establish dorsal boundaries of genes expressed along the dorsal-ventral (DV) axis of early Drosophila embryos, while repressors establish ventral boundaries. Yet recent studies have provided evidence that repressors act to specify the dorsal boundary of intermediate neuroblasts defective (ind), a gene expressed in a stripe along the DV axis in lateral regions of the embryo. Here we show that a short 12 base pair sequence (“the A-box”) present twice within the ind CRM is both necessary and sufficient to support transcriptional repression in dorsal regions of embryos. To identify binding factors, we conducted affinity chromatography using the A-box element and found a number of DNA-binding proteins and chromatin-associated factors using mass spectroscopy. Only Grainyhead (Grh), a CP2 transcription factor with a unique DNA-binding domain, was found to bind the A-box sequence. Our results suggest that Grh acts as an activator to support expression of ind, which was surprising as we identified this factor using an element that mediates dorsally-localized repression. Grh and Dorsal both contribute to ind transcriptional activation. However, another recent study found that the repressor Capicua (Cic) also binds to the A-box sequence. While Cic was not identified through our A-box affinity chromatography, utilization of the same site, the A-box, by both factors Grh (activator) and Cic (repressor) may also support a “switch-like” response that helps to sharpen the ind dorsal boundary. Furthermore, our results also demonstrate that TGF-β signaling acts to refine ind CRM expression in an A-box independent manner in dorsal-most regions, suggesting that tiers of repression act in dorsal regions of the embryo

Molecular requirements involving the human platelet protease-activated receptor-4 mechanism of activation by peptide analogues of its tetheredligand

Thrombin is the most potent agonist of human platelets and its effects are primarily mediated through the protease-activated receptors (PARs)-1 and -4. Although PAR-1 has higher affinity for thrombin than PAR-4, both receptors contribute to thrombin-mediated actions on platelets. Recently, a potent and selective PAR-1 antagonist (vorapaxar) was approved for clinical use in selected patients. In contrast, despite the fact that several PAR-4 antagonists have been developed, few of them have been tested in clinical trials. The aim of the present study was to elucidate the molecular requirements involving the PAR-4 mechanism of activation by peptide analogues of its tethered-ligand. Eight synthetic PAR-4 tethered-ligand peptide analogues were synthesized and studied for their agonistic/antagonistic potency and selectivity toward human washed platelet aggregation, using light transmittance aggregometry. In addition, in silico studies were conducted to describe the receptor–peptide interactions that are developed following PAR-4 exposure to the above analogues. To provide a first structure-activity relationship rationale on the bioactivity profiles recorded for the studied analogues, molecular docking was applied in a homology model of PAR-4, derived using the crystal structure of PAR-1. The following peptide analogues were synthesized: AYPGKF-NH2 (1), GYPGKF-NH2 (2), AcAYPGKF-NH2 (3), trans-cinnamoyl-AYPGKF-NH2 (4), YPGKF-NH2 (5), Ac-YPGKF-NH2 (6), transcinnamoyl-YPGKF-NH2 (7), and caffeoyl-YPGKF-NH2 (8). Peptide (1) is a selective PAR-4 agonist inducing platelet aggregation with an IC50 value of 26.2 μM. Substitution of Ala-1 with Gly-1 resulted in peptide (2), which significantly reduces the agonistic potency of peptide (1) by 25- fold. Importantly, substitution of Ala-1 with trans-cinnamoyl-1 resulted in peptide (7), which completely abolishes the agonistic activity of peptide (1) and renders it with a potent antagonistic activity toward peptide (1)-induced platelet aggregation. All other peptides tested were inactive. Tyr-2, residue, along with its neighboring environment was a key determinant in the PAR-4 recognition mode. When the neighboring residues to Tyr-2 provided an optimum spatial ability for the ligand to enter into the binding site of the transmembrane receptor, a biological response was propagated. These results were compared with the predicted binding poses of small molecule antagonists of PAR-4, denoted as YD-3, ML-354, and BMS-986120. π–π stacking interaction with Tyr-183 appears to be critical and common for both small molecules antagonists and the peptide trans-cinnamoyl-YPGKFNH2. Conclusively, the lipophilicity, size, and aromatic nature of the residue preceding Tyr-2 are determining factors on whether a human platelet PAR-4 tethered-ligand peptide analogue will exert an agonistic or antagonistic activit

Augmenting forearm crutches with wireless sensors for lower limb rehabilitation

Forearm crutches are frequently used in the rehabilitation of an injury to the lower limb. The recovery rate is improved if the patient correctly applies a certain fraction of their body weight (specified by a clinician) through the axis of the crutch, referred to as partial weight bearing (PWB). Incorrect weight bearing has been shown to result in an extended recovery period or even cause further damage to the limb. There is currently no minimally invasive tool for long-term monitoring of a patient's PWB in a home environment. This paper describes the research and development of an instrumented forearm crutch that has been developed to wirelessly and autonomously monitor a patient's weight bearing over the full period of their recovery, including its potential use in a home environment. A pair of standard forearm crutches are augmented with low-cost off-the-shelf wireless sensor nodes and electronic components to provide indicative measurements of the applied weight, crutch tilt and hand position on the grip. Data are wirelessly transmitted between crutches and to a remote computer (where they are processed and visualized in LabVIEW), and the patient receives biofeedback by means of an audible signal when they put too much or too little weight through the crutch. The initial results obtained highlight the capability of the instrumented crutch to support physiotherapists and patients in monitoring usage

Adult brain abscess associated with patent foramen ovale: a case report

Brain abscess results from local or metastatic septic spread to the brain. The primary infectious site is often undetected, more commonly so when it is distant. Unlike pediatric congenital heart disease, minor intracardiac right-to-left shunting due to patent foramen ovale has not been appreciated as a cause of brain abscess in adults. Here we present a case of brain abscess associated with a patent foramen ovale in a 53-year old man with dental-gingival sepsis treated in the intensive care unit. Based on this case and the relevant literature we suggest a link between a silent patent foramen ovale, paradoxic pathogen dissemination to the brain, and development of brain abscess