Use of computational fluid dynamics to compare upper airway pressures and airflow resistance in brachycephalic, mesocephalic, and dolichocephalic dogs

Brachycephalic dog breeds are prone to breathing difficulties because of their upper airway anatomy. Several surgical techniques exist to correct anatomical pathologies and common surgical approaches aim to correct functional abnormalities in the nares and/or the soft palate. However, further research is needed to improve clinical outcomes. This study evaluated air pressure and airflow resistance in the upper airways and trachea in nine sedated, sternally recumbent dogs of different skull types (dolichocephalic, n = 3; mesocephalic, n = 3; brachycephalic, n = 3). CT images were acquired from the nostrils to the caudal border of the lungs and geometrical reconstruction of the upper airway and trachea was performed. Analysis of computational fluid dynamics was performed using inspiratory flow adapted to bodyweight for each dog. Flow (L/min) and pressure (cmH2O) were computed for the entire upper airway and trachea. Resistance (cmH2O/L/min) was calculated using pressure differences between the nose, larynx, and trachea. In this pilot study, statistical comparisons were not performed. Pressure maps, airflow, and resistance were similar in dolichocephalic and mesocephalic breeds. Median pressure difference (3.76 cmH2O) and resistance (0.154 cmH2O/L/min) between the nose and larynx were numerically higher in brachycephalic dogs than in other breeds (0.45 cmH2O and 0.016 cmH2O/L/min, respectively). Median pressure difference (0.205 cmH2O) and resistance (0.009 cmH2O/L/min) between the larynx and trachea was numerically similar in all dogs, except for the English bulldog. The methodology used in this preliminary study to quantify airflow characteristics such as pressure and resistance could improve the understanding of brachycephalic obstruction airway syndrome

Application of Max-SAT-based ATPG to optimal cancer therapy design

BACKGROUND: Cancer and other gene related diseases are usually caused by a failure in the signaling pathway between genes and cells. These failures can occur in different areas of the gene regulatory network, but can be abstracted as faults in the regulatory function. For effective cancer treatment, it is imperative to identify faults and select appropriate drugs to treat the faults. In this paper, we present an extensible Max-SAT based automatic test pattern generation (ATPG) algorithm for cancer therapy. This ATPG algorithm is based on Boolean Satisfiability (SAT) and utilizes the stuck-at fault model for representing signaling faults. A weighted partial Max-SAT formulation is used to enable efficient selection of the most effective drug. RESULTS: Several usage cases are presented for fault identification and drug selection. These cases include the identification of testable faults, optimal drug selection for single/multiple known faults, and optimal drug selection for overall fault coverage. Experimental results on growth factor (GF) signaling pathways demonstrate that our algorithm is flexible, and can yield an exact solution for each feature in much less than 1 second

Imaging features of retroperitoneal extra-adrenal paragangliomas in 10 dogs

Retroperitoneal paragangliomas are rare tumors of the neuroendocrine system. Only a few canine case reports are available with rare descriptions of their imaging features. The objectives of this multi-center, retrospective case series study were to describe the diagnostic imaging features of confirmed retroperitoneal paragangliomas and specify their location. Medical records and imaging studies of 10 affected dogs with cytological or histopathologic results concordant with retroperitoneal paragangliomas were evaluated. Dogs had a median age of 9 years. Four of them had clinical signs and laboratory reports compatible with excessive production of catecholamines. Six ultrasound, four CT, four radiographic, and one MRI studies were included. The paragangliomas did not have a specific location along the aorta. They were of various sizes (median 33 mm, range: 9–85 mm of length). Masses had heterogeneous parenchyma in six of 10 dogs, regardless of the imaging modality. Strong contrast enhancement was found in all CT studies. Encircling of at least one vessel was detected in six of 10 masses, clear invasion of a vessel was identified in one of 10 masses. In five of 10 cases, the masses were initially misconstrued as lymph nodes by the on-site radiologist. Retroperitoneal paragangliomas appear along the abdominal aorta, often presenting heterogeneous parenchyma, possibly affecting the local vasculature, and displaying strong contrast enhancement on CT. Clinical signs can be secondary to mass effects or excessive catecholamine production. Underdiagnosis and misdiagnosis of this tumor are suspected as they can be silent, of small size, or confused with other structures

Spatially Controlled Generation and Probing of Random Telegraph Noise in Metal Nanocrystal Embedded HfO2Using Defect Nanospectroscopy

Random telegraph noise (RTN) is often considered a nuisance or, more critically, a key reliability challenge for miniaturized semiconductor devices. However, this picture is gradually changing as recent works have shown emerging applications based on the inherent randomness of the RTN signals in state-of-The-Art technologies, including true random number generator and IoT hardware security. Suitable material platforms and device architectures are now actively explored to bring these technologies from an embryonic stage to practical application. A key challenge is to devise material systems, which can be reliably used for the deterministic creation of localized defects to be used for RTN generation. Toward this goal, we have investigated RTN in Au nanocrystal (Au-NC) embedded HfO2stacks at the nanoscale by combining conduction atomic force microscopy defect spectroscopy and a statistical factorial hidden Markov model analysis. With a voltage applied across the stack, there is an enhanced asymmetric electric field surrounding the Au-NC. This in turn leads to the preferential generation of atomic defects in the HfO2near the Au-NC when voltage is applied to the stack to induce dielectric breakdown. Since RTN arises from various electrostatic interactions between closely spaced atomic defects, the Au-NC HfO2material system exhibits an intrinsic ability to generate RTN signals. Our results also highlight that the spatial confinement of multiple defects and the resulting electrostatic interactions between the defects provides a dynamic environment leading to many complex RTN patterns in addition to the presence of the standard two-level RTN signals. The insights obtained at the nanoscale are useful to optimize metal nanocrystal embedded high-κ stacks and circuits for on-demand generation of RTN for emerging random number applications

A single evolutionarily divergent mutation determines the different FAD-binding affinities of human and rat NQO1 due to site-specific phosphorylation

The phosphomimetic mutation S82D in the cancer-associated, FAD-dependent human NADP(H):quinone oxidoreductase 1 (hNQO1) causes a decrease in flavin-adenine dinucleotide-binding affinity and intracellular stability. We test in this work whether the evolutionarily recent neutral mutation R80H in the vicinity of S82 may alter the strong functional effects of S82 phosphorylation through electrostatic interactions. We show using biophysical and bioinformatic analyses that the reverse mutation H80R prevents the effects of S82D phosphorylation on hNQO1 by modulating the local stability. Consistently, in rat NQO1 (rNQO1) which contains R80, the effects of phosphorylation were milder, resembling the behaviour found in hNQO1 when this residue was humanized in rNQO1 (by the R80H mutation). Thus, apparently neutral and evolutionarily divergent mutations may determine the functional response of mammalian orthologues towards phosphorylation. © 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societie

Structural basis of the pleiotropic and specific phenotypic consequences of missense mutations in the multifunctional NAD(P)H:quinone oxidoreductase 1 and their pharmacological rescue

The multifunctional nature of human flavoproteins is critically linked to their ability to populate multiple conformational states. Ligand binding, post-translational modifications and disease-associated mutations can reshape this functional landscape, although the structure-function relationships of these effects are not well understood. Herein, we characterized the structural and functional consequences of two mutations (the cancer-associated P187S and the phosphomimetic S82D) on different ligation states which are relevant to flavin binding, intracellular stability and catalysis of the disease-associated NQO1 flavoprotein. We found that these mutations affected the stability locally and their effects propagated differently through the protein structure depending both on the nature of the mutation and the ligand bound, showing directional preference from the mutated site and leading to specific phenotypic manifestations in different functional traits (FAD binding, catalysis and inhibition, intracellular stability and pharmacological response to ligands). Our study thus supports that pleitropic effects of disease-causing mutations and phosphorylation events on human flavoproteins may be caused by long-range structural propagation of stability effects to different functional sites that depend on the ligation-state and site-specific perturbations. Our approach can be of general application to investigate these pleiotropic effects at the flavoproteome scale in the absence of high-resolution structural models. © 202

The Effects of Particulate Matter Sources on Daily Mortality: A Case-Crossover Study of Barcelona, Spain

Background: Dozens of studies link acute exposure to particulate matter (PM) air pollution with premature mortality and morbidity, but questions remain about which species and sources in the vast PM mixture are responsible for the observed health effects. Although a few studies exist on the effects of species and sources in U.S. cities, European cities—which have a higher proportion of diesel engines and denser urban populations—have not been well characterized. Information on the effects of specific sources could aid in targeting pollution control and in articulating the biological mechanisms of PM

Understanding and predicting trends in urban freight transport

Among different components of urban mobility, urban freight transport is usually considered as the least sustainable. Limited traffic infrastructures and increasing demands in dense urban regions lead to frequent delivery runs with smaller freight vehicles. This increases the traffic in urban areas and has negative impacts upon the quality of life in urban populations. Data driven optimizations are essential to better utilize existing urban transport infrastructures and to reduce the negative effects of freight deliveries for the cities. However, there is limited work and data driven research on urban delivery areas and freight transportation networks. In this paper, we collect and analyse data on urban freight deliveries and parking areas towards an optimized urban freight transportation system. Using a new check-in based mobile parking system for freight vehicles, we aim to understand and optimize freight distribution processes. We explore the relationship between areas' availability patterns and underlying traffic behaviour in order to understand the trends in urban freight transport. By applying the detected patterns we predict the availabilities of loading/unloading areas, and thus open up new possibilities for delivery route planning and better managing of freight transport infrastructures. © 2017 IEEE

Observational consequences of fine structure line optical depths on infrared spectral diagnostics

It has long been known that infrared fine structure lines of abundant ions, like the [O III] 88 micron line, can become optically thick in H II regions under certain high luminosity conditions. This could mitigate their potential as diagnostic tools, especially if the source is too dusty for optical spectroscopy to otherwise determine the system's parameters. We examined a series of photoionization calculations which were designed to push the nebulae into the limit where many IR lines should be quite optically thick. We find that radiative transfer effects do not significantly change the observed emission line spectrum. This is due to a combination of grain absorption of the hydrogen ionizing continuum and the fact that the correction for stimulated emission in these lines is large. Given these results, and the likelihood that real objects have non-thermal line broadening, it seems unlikely that line optical depth presents a problem in using these lines as diagnostics of the physical conditions or chemical composition.Comment: 16 pages, 4 figures, to be published in the February 2003 issue of the PAS

Fish mitigate trophic depletion in marine cave ecosystems.

Dark marine habitats are often characterized by a food-limited condition. Peculiar dark habitats include marine caves, characterized by the absence of light and limited water flow, which lead to reduced fluxes of organic matter for cave-dwelling organisms. We investigated whether the most abundant and common cave-dwelling fish Apogon imberbis has the potential to play the role of trophic vector in Mediterranean marine caves. We first analysed stomach contents to check whether repletion changes according to a nycthemeral cycle. We then identified the prey items, to see whether they belong to species associated with cave habitats or not. Finally, we assessed whether A. imberbis moves outside marine caves at night to feed, by collecting visual census data on A. imberbis density both inside and outside caves, by day and by night. The stomach repletion of individuals sampled early in the morning was significantly higher than later in the day. Most prey were typical of habitats other than caves. A. imberbis was on average more abundant within caves during the day and outside during the night. Our study supports the hypothesis regarding the crucial trophic role of A. imberbis in connecting Mediterranean marine caves with external habitat