A conservative coupling algorithm between a compressible flow and a rigid body using an Embedded Boundary method

This paper deals with a new solid-fluid coupling algorithm between a rigid body and an unsteady compressible fluid flow, using an Embedded Boundary method. The coupling with a rigid body is a first step towards the coupling with a Discrete Element method. The flow is computed using a Finite Volume approach on a Cartesian grid. The expression of numerical fluxes does not affect the general coupling algorithm and we use a one-step high-order scheme proposed by Daru and Tenaud [Daru V,Tenaud C., J. Comput. Phys. 2004]. The Embedded Boundary method is used to integrate the presence of a solid boundary in the fluid. The coupling algorithm is totally explicit and ensures exact mass conservation and a balance of momentum and energy between the fluid and the solid. It is shown that the scheme preserves uniform movement of both fluid and solid and introduces no numerical boundary roughness. The effciency of the method is demonstrated on challenging one- and two-dimensional benchmarks

Clinical assessment of fluorescence cystoscopy during transurethral bladder resection in superficial bladder cancer

The prognosis of superficial bladder cancer in terms of recurrence and disease progression is related to bladder tumor multiplicity and the presence of concomitant "plane” tumors such as high-grade dysplasia and carcinoma in situ. This study in 33 patients aimed to demonstrate the role of fluorescence cystoscopy in transurethral resection of superficial bladder cancer. The method is based on the detection of protoporphyrin-IX-induced fluorescence in urothelial cancer cells by topical administration of 5-aminolevulinic acid. The sensitivity and the specificity of this procedure on apparently normal mucosa in superficial bladder cancer are estimated to be 82.9% and 81.3%, respectively. Thus, fluorescence cytoscopy is a simple and reliable method for mapping the bladder mucosa, especially in the case of multifocal bladder disease, and it facilitates the screening of occult dysplasi

Revisiting the Local Scaling Hypothesis in Stably Stratified Atmospheric Boundary Layer Turbulence: an Integration of Field and Laboratory Measurements with Large-eddy Simulations

The `local scaling' hypothesis, first introduced by Nieuwstadt two decades ago, describes the turbulence structure of stable boundary layers in a very succinct way and is an integral part of numerous local closure-based numerical weather prediction models. However, the validity of this hypothesis under very stable conditions is a subject of on-going debate. In this work, we attempt to address this controversial issue by performing extensive analyses of turbulence data from several field campaigns, wind-tunnel experiments and large-eddy simulations. Wide range of stabilities, diverse field conditions and a comprehensive set of turbulence statistics make this study distinct

The impact of childhood trauma and psychophysiological reactivity on at-risk women's adjustment to parenthood

Adverse childhood experiences (ACEs) have an impact on women's adaptation to parenthood, but mechanisms are poorly understood. Autonomic nervous system reactivity was tested as a potential mediating mechanism in a sample of 193 at-risk primiparous women. ACEs were measured retrospectively during pregnancy. A baby cry-response task was administered during pregnancy while indicators of sympathetic reactivity (pre-ejection period; PEP) and parasympathetic reactivity (respiratory sinus arrhythmia; RSA) were recorded. Parenting self-efficacy, anxiety, and depressive symptoms were measured during pregnancy and 1 year after giving birth. Harsh discipline was measured 2 years after giving birth. Structural equation modeling was employed to test whether baseline PEP and RSA and reactivity mediated links between ACEs and postnatal outcomes, adjusted for prenatal variables. High ACEs predicted less RSA reactivity (p =.02), which subsequently predicted increases in depressive symptoms (p =.03). The indirect effect was not significant (p =.06). There was no indirect link between high ACEs and harsh parenting through PEP nor RSA (n = 98). The parasympathetic nervous system may be involved in negative affective responses in the transition to parenthood among women exposed to childhood trauma

Discrete Kinetic Models from Funneled Energy Landscape Simulations

A general method for facilitating the interpretation of computer simulations of protein folding with minimally frustrated energy landscapes is detailed and applied to a designed ankyrin repeat protein (4ANK). In the method, groups of residues are assigned to foldons and these foldons are used to map the conformational space of the protein onto a set of discrete macrobasins. The free energies of the individual macrobasins are then calculated, informing practical kinetic analysis. Two simple assumptions about the universality of the rate for downhill transitions between macrobasins and the natural local connectivity between macrobasins lead to a scheme for predicting overall folding and unfolding rates, generating chevron plots under varying thermodynamic conditions, and inferring dominant kinetic folding pathways. To illustrate the approach, free energies of macrobasins were calculated from biased simulations of a non-additive structure-based model using two structurally motivated foldon definitions at the full and half ankyrin repeat resolutions. The calculated chevrons have features consistent with those measured in stopped flow chemical denaturation experiments. The dominant inferred folding pathway has an “inside-out”, nucleation-propagation like character

Adhiron: a stable and versatile peptide display scaffold for molecular recognition applications

We have designed a novel non-antibody scaffold protein, termed Adhiron, based on a phytocystatin consensus sequence. The Adhiron scaffold shows high thermal stability (Tm ca. 101°C), and is expressed well in Escherichia coli. We have determined the X-ray crystal structure of the Adhiron scaffold to 1.75 Å resolution revealing a compact cystatin-like fold. We have constructed a phage-display library in this scaffold by insertion of two variable peptide regions. The library is of high quality and complexity comprising 1.3 × 10(10) clones. To demonstrate library efficacy, we screened against the yeast Small Ubiquitin-like Modifier (SUMO). In selected clones, variable region 1 often contained sequences homologous to the known SUMO interactive motif (V/I-X-V/I-V/I). Four Adhirons were further characterised and displayed low nanomolar affinities and high specificity for yeast SUMO with essentially no cross-reactivity to human SUMO protein isoforms. We have identified binders against >100 target molecules to date including as examples, a fibroblast growth factor (FGF1), platelet endothelial cell adhesion molecule (PECAM-1; CD31), the SH2 domain Grb2 and a 12-aa peptide. Adhirons are highly stable and well expressed allowing highly specific binding reagents to be selected for use in molecular recognition applications

High altitudes and partial pressure of arterial oxygen in patients with chronic obstructive pulmonary disease - A systematic review and meta-analysis

Importance: Prior study in healthy subjects has shown a reduction of partial pressure of arterial oxygen (PaO$_{2}$) by -1.60 kPa/kilometre of altitude gain. However, the association of altitude-related change in PaO$_{2}$ and altitude-related adverse health effects (ARAHE) in patients with chronic obstructive pulmonary disease (COPD) remain unknown. Objective: To provide an effect size estimate for the decline in PaO$_{2}$ with each kilometre of altitude gain and to identify ARAHE in relation to altitude in patients with COPD. www.crd.york.ac.uk/prospero: CRD42020217938. Data sources: A systematic search of PubMed and Embase was performed from inception to May 30, 2023. Study selection: Peer-reviewed and prospective studies in patients with COPD staying at altitudes >1500 m providing arterial blood gases within the first 3 days at the target altitude. Data extraction and synthesis: Aggregate data (AD) on study characteristics were extracted, and individual patient data (IPD) were requested. Estimates were pooled using random-effects meta-analysis. Main outcome and measures: Relative risk estimates and 95 % confidence intervals for the association between PaO$_{2}$ and altitude in patients with COPD. Results: Thirteen studies were included in the AD analysis, of which 6 studies (222 patients, 45.2 % female) provided IPD, thus were included in the quantitative analysis. The estimated effect size of PaO$_{2}$ was -0.84 kPa [95 %CI, -0.92 to -0.76] per 1000 m of altitude gain (I$^{2}$=65.0 %, P < 0.001). In multivariable regression analysis, COPD severity, baseline PaO$_{2}$, age and time spent at altitude were predictors for PaO$_{2}$ at altitude. Overall, 37.8 % of COPD patients experienced an ARAHE, whereas older age, female sex, COPD severity, baseline PaO$_{2}$, and target altitude were predictors for the occurrence of ARAHE (area under ROC curve: 0.9275, P < 0.001). Conclusions and relevance: This meta-analysis, providing altitude-related decrease in PaO$_{2}$ and risk of ARAHE in patients with COPD ascending to altitudes >1500 m, revealed a lower altitude-related decrease in PaO$_{2}$ in COPD patients compared with healthy. However, these findings might improve patient care and facilitate decisions about initiating preventive measures against hypoxaemia and ARAHE in patients with COPD planning an altitude sojourn or intercontinental flight, i.e. supplemental oxygen or acetazolamide

Active Connections: Means For Faculty To Create An Environment In Which Students WANT To Engage!

This interactive, cross-disciplinary research explores face-to-face and online strategies for faculty to deploy in the classroom that encourage connections beyond forced engagement methodologies commonly used. Concentration is on methods of connecting that are “out of the mainstream” and benefit both students and faculty. Findings indicate that the more students feel as a valued participant of the learning community, the more they engage in the class activities

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

Exogenous administration of 5-aminolaevulinic acid (ALA) is becoming widely used to enhance the endogenous synthesis of protoporphyrin IX (PpIX) in photodynamic therapy (PDT) and fluorescence photodetection (PD). Recently, results have shown that the chemical modification of ALA into its more lipophilic esters circumvents limitations of ALA-induced PpIX like shallow penetration depth into deep tissue layers and inhomogeneous biodistribution and enhances the total PpIX formation. The present clinical pilot study assesses the feasibility and the advantages of a topical ALA ester-based fluorescence photodetection in the human bladder. In this preliminary study 5-aminolaevulinic acid hexylester (h-ALA) solutions, containing concentrations ranging from 4 to 16 mM, were applied intravesically to 25 patients. Effects of time and drug dose on the resulting PpIX fluorescence level were determined in vivo with an optical fibre-based spectrofluorometer. Neither local nor systemic side-effects were observed for the applied conditions. All conditions used yielded a preferential PpIX accumulation in the neoplastic tissue. Our clinical investigations indicate that with h-ALA a twofold increase of PpIX fluorescence intensity can be observed using 20-fold lower concentrations as compared to ALA

Last Men Standing: Chlamydatus Portraits and Public Life in Late Antique Corinth

Notable among the marble sculptures excavated at Corinth are seven portraits of men wearing the long chlamys of Late Antique imperial office. This unusual costume, contemporary portrait heads, and inscribed statue bases all help confirm that new public statuary was created and erected at Corinth during the 4th and 5th centuries. These chlamydatus portraits, published together here for the first time, are likely to represent the Governor of Achaia in his capital city, in the company of local benefactors. Among the last works of the ancient sculptural tradition, they form a valuable source of information on public life in Late Antique Corinth