Influence of diesel surrogates on the behavior of simplified spray models

Numerous experimental investigations make use of diesel surrogates to make the computational time reasonable. In the few studies where measured (surrogate and real diesel) and computed (surrogate only) results have been compared, the selection methodology for the surrogate constituent compounds and the measures taken to validate the chemical kinetic models are not discussed, and the range of operating conditions used is often small. Additionally, most simplified models use tuning variables to fit model results to measurements. This work makes the comparison between some frequently used diesel surrogates using a simple 1D vaporizing spray model, with the spray cone angle as the tuning parameter. Results show that liquid length and fuel fraction strongly depend on the physical properties of the used fuel for a fixed spray angle. These parameters are important for modeling auto-ignition and pollutant formation. The spray angle is varied till the spray length is the same for each surrogate. Results show important differences between other spray parameters such as local mixture fraction and axial velocity

Enhancement of Gap Junction Function During Acute Myocardial Infarction Modifies Healing and Reduces Late Ventricular Arrhythmia Susceptibility

Objectives: To investigate the effects of enhancing gap junction (GJ) coupling during acute myocardial infarction (MI) on the healed infarct scar morphology and late post-MI arrhythmia susceptibility. Background: Increased heterogeneity of myocardial scarring after MI is associated with greater arrhythmia susceptibility. We hypothesized that short-term enhancement of GJ coupling during acute MI can produce more homogeneous infarct scars, reducing late susceptibility to post-MI arrhythmias. Methods: Following arrhythmic characterisation of the rat 4-week post-MI model (n=24), a further 27 Sprague-Dawley rats were randomised to receive rotigaptide to enhance GJ coupling (n=13) or saline control (n=14) by osmotic minipump immediately prior to, and for the first 7 days following surgical MI. At 4 weeks post-MI, hearts were explanted for ex vivo programmed electrical stimulation (PES) and optical mapping. Heterogeneity of infarct border zone (IBZ) scarring was quantified by histomorphometry. Results: Despite no detectable difference in infarct size at 4 weeks post-MI, rotigaptide-treated hearts had reduced arrhythmia susceptibility during PES (Inducibility score: rotigaptide 2.40.8, control 5.00.6, p=0.02) and less heterogeneous IBZ scarring (standard deviation of IBZ Complexity Score: rotigaptide 1.10.1, control 1.40.1, p=0.04), associated with an improvement in IBZ conduction velocity (rotigaptide 43.13.4 cm/s, control 34.82.0 cm/s, p=0.04). Conclusions: Enhancement of GJ coupling for only 7 days at the time of acute MI produced more homogeneous IBZ scarring and reduced arrhythmia susceptibility at 4 weeks post-MI. Short-term GJ modulation at the time of MI may represent a novel treatment strategy to modify the healed infarct scar morphology and reduce late post-MI arrhythmic risk

Arrhythmic Genotypes in Familial Dilated Cardiomyopathy: Implications for Genetic Testing and Clinical Management

Cardiac arrhythmias are frequently seen in patients with dilated cardiomyopathy (DCM) and can precipitate heart failure and death. In patients with non-ischaemic DCM, evidence for the benefit of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death has recently been questioned. Algorithms devised to identify high-risk individuals who might benefit most from ICD implantation have focussed on clinical criteria with little attention paid to the underlying aetiology of DCM. Malignant ventricular arrhythmias often occur as a nonspecific consequence of DCM but can also be a primary manifestation of disease in heritable forms of DCM and may precede DCM onset. We undertook a literature search and identified 11 genes that have been associated with DCM and ventricular arrhythmias in multiple kindreds. Many of these genes fall into a diagnostic grey zone between left-dominant arrhythmogenic right ventricular cardiomyopathy and arrhythmic DCM. Genes associated predominantly with arrhythmic DCM included LMNA and SCN5A, as well as the more recently-reported DCM disease genes, RBM20, FLNC, and TTN. Recognition of arrhythmic DCM genotypes is important, as this may impact on clinical management. In particular, prophylactic ICD implantation and early referral for heart transplantation may be indicated in genotype-positive individuals. Collectively, these findings argue in favour of including genetic testing in standard-of-care management of familial DCM. Further studies in genotyped patient cohorts are required to establish the long-term health and economic benefits of this strategy

Igneous rock area and age in continental crust

Abstract Rock quantity and age are fundamental features of Earth's crust that pertain to many problems in geoscience. Here we combine new estimates of igneous rock area in continental crust from the Macrostrat database (https://macrostrat.org/) with a compilation of detrital zircon ages in order to investigate rock cycling and crustal growth. We find that there is little or no decrease in igneous rock area with increasing rock age. Instead, igneous rock area in North America exhibits four distinct Precambrian peaks, remains low through the Neoproterozoic, and then increases only modestly toward the recent. Peaks in Precambrian detrital zircon age frequency distributions align broadly with peaks in igneous rock area, regardless of grain depositional age. However, detrital zircon ages do underrepresent a Neoarchean peak in igneous rock area; young grains and ca. 1.1 Ga grains are also overrepresented relative to igneous area. Together, these results suggest that detrital zircon age distributions contain signatures of continental denudation and sedimentary cycling that are decoupled from the cycling of igneous source rocks. Models of continental crustal evolution that incorporate significant early increase in volume and increased sedimentation in the Phanerozoic are well supported by these data.</jats:p

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

Tools for analyzing parallel I/O

Parallel application I/O performance often does not meet user expectations. Additionally, slight access pattern modifications may lead to significant changes in performance due to complex interactions between hardware and software. These issues call for sophisticated tools to capture, analyze, understand, and tune application I/O. In this paper, we highlight advances in monitoring tools to help address these issues. We also describe best practices, identify issues in measure- ment and analysis, and provide practical approaches to translate parallel I/O analysis into actionable outcomes for users, facility operators, and researchers

Four-jointed knock-out delays renal failure in an ADPKD model with kidney injury

Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid-filled cysts in the kidneys which lead to end-stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the Pkd1 gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in Pkd1 knock-out (KO) mice. In that study, we found that after injury four-jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in Pkd1 KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury/repair and cyst formation. We generated single and double deletion mice for Pkd1 and Fjx1, and we induced toxic renal injury using the nephrotoxic compound 1,2-dichlorovinyl-cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in Pkd1 mutant mice. This caused Pkd1 KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that Fjx1 disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Quantification of Cre-mediated recombination by a novel strategy reveals a stable extra-chromosomal deletion-circle in mice

<p>Abstract</p> <p>Background</p> <p>Inducible conditional knockout animals are widely used to get insight in the function of genes and the pathogenesis of human diseases. These models frequently rely on Cre-mediated recombination of sequences flanked by Lox-P sites. To understand the consequences of gene disruption, it is essential to know the efficiency of the recombination process.</p> <p>Results</p> <p>Here, we describe a modification of the multiplex ligation-dependent probe amplification (MLPA), called extension-MLPA (eMLPA), which enables quantification of relatively small differences in DNA that are a consequence of Cre-mediated recombination. eMLPA, here applied on an inducible <it>Pkd1 </it>conditional deletion mouse model, simultaneously measures both the reduction of the floxed allele and the increase of the deletion allele in a single reaction thereby minimizing any type of experimental variation. Interestingly, with this method we were also able to observe the presence of the excised DNA fragment. This extra-chromosomal deletion-circle was detectable up to 5 months after activation of Cre.</p> <p>Conclusion</p> <p>eMLPA is a novel strategy which easily can be applied to measure the Cre-mediated recombination efficiency in each experimental case with high accuracy. In addition the fate of the deletion-circle can be followed simultaneously.</p

Initial fixation placement in face images is driven by top-down guidance

The eyes are often inspected first and for longer period during face exploration. To examine whether this saliency of the eye region at the early stage of face inspection is attributed to its local structure properties or to the knowledge of its essence in facial communication, in this study we investigated the pattern of eye movements produced by rhesus monkeys (Macaca mulatta) as they free viewed images of monkey faces. Eye positions were recorded accurately using implanted eye coils, while images of original faces, faces with scrambled eyes, and scrambled faces except for the eyes were presented on a computer screen. The eye region in the scrambled faces attracted the same proportion of viewing time and fixations as it did in the original faces, even the scrambled eyes attracted substantial proportion of viewing time and fixations. Furthermore, the monkeys often made the first saccade towards to the location of the eyes regardless of image content. Our results suggest that the initial fixation placement in faces is driven predominantly by ‘top-down’ or internal factors, such as the prior knowledge of the location of “eyes” within the context of a face

Pharmacogenomic insights into treatment and management of statin-induced myopathy

Although statins are generally well tolerated, the most common adverse drug reaction from statin therapy is myopathy. This article reviews the current pharmacogenomic knowledge of statin-induced myopathy. Furthermore, we will discuss the importance of recent pharmacogenetic advances for the treatment and management of statin-induced myopathy. Variation in the SLCO1B1 gene is associated with increased incidence of statin-induced myopathy, particularly with simvastatin and less so with other statins. If different pharmacokinetic enzymes and transporters are responsible for susceptibility to myopathy, this may explain differences in the occurrence of statin-induced myopathy in individual patients. Genotyping in patients suffering from statin-induced myopathy may help to personalize the choice of statin for the lowest chance of developing myopathy