Changes in micro- and central hemodynamic parameters in rats under the action of acetylsalicylic acid and its coordination compounds with metals

Introduction. The cutaneous blood circulation is a representative model both for studying the mechanisms of vascular diseases and for assessing the current state of the central hemodynamics in preclinical researches of various chemical compounds. Aim. The changes in the parameters of cutaneous microcirculation and central hemodynamics (heart rate and blood pressure) were studied in the animals under the action of acetylsalicylic acid and its coordination compounds with cations of cobalt, zinc, nickel and manganese at a dose of 20 mg/kg. Materials and methods. The research was conducted using the laser Doppler flowmetry method on the Lazma-MC device (manufactured by RPE Lazma, Russia) and the NIBP200A system (Biopac Systems, Inc., USA). Results. The study shows that animals develop bradycardia, and microcirculation and central hemodynamics change in two ways after the introduction of acetylsalicylic acid and the tested metal salicylates. These ways are hypotension-related hyperemia (acetylsalicylic acid and cobalt salicylate) and ischemia (zinc, nickel and manganese salicylates) associated with hypertension. Conclusion. The obtained data confirm the cardiotropic activity of new coordination compounds. The data also prove that the generation of the acetylsalicylic acid derivatives allows enhancing it physiological effects, as well as obtaining completely new molecules. The molecules are different from the precursor one and are necessary for the production of effective drugs.

Measuring context dependency in birdsong using artificial neural networks

Context dependency is a key feature in sequential structures of human language, which requires reference between words far apart in the produced sequence. Assessing how long the past context has an effect on the current status provides crucial information to understand the mechanism for complex sequential behaviors. Birdsongs serve as a representative model for studying the context dependency in sequential signals produced by non-human animals, while previous reports were upper-bounded by methodological limitations. Here, we newly estimated the context dependency in birdsongs in a more scalable way using a modern neural-network-based language model whose accessible context length is sufficiently long. The detected context dependency was beyond the order of traditional Markovian models of birdsong, but was consistent with previous experimental investigations. We also studied the relation between the assumed/auto-detected vocabulary size of birdsong (i.e., fine- vs. coarse-grained syllable classifications) and the context dependency. It turned out that the larger vocabulary (or the more fine-grained classification) is assumed, the shorter context dependency is detected.

Numerical Study to Assess the Structural Behavior of the Bajrakli Mosque (Western Kosovo)

Cultural heritage is one of most significant concerns in modern societies carrying different social and historical values. Among the stock of cultural heritage, historical monuments are one of the greatest contributors to the values in many aspects. Due to several factors, such structures have gone through changes causing structural deficiencies. The aim of this study is to provide a clear insight of the cause and impacts of structural deficiencies through visual inspections and computational methods. As a representative model, Bajrakli Mosque located in western of Kosovo is selected as a case study. During visual inspections, some cracks are found along the structural elements of the mosque. A possible cause of the structural cracks may be the stress concentration through the regions of the structure. In order to provide a better understanding, two different loadings are considered to examine the structural behavior of the mosque. The first loading covers the analysis due to gravity loads, whereas the second one defines the dynamic loading due to ground shakings defined by the earthquake spectrum using finite element analysis in SAP2000. By means of these analyses, the performance of the building is examined. As a result, important data are obtained for identifying the critical regions of the structure. The maximum displacement of the structure is found to be 7.1 mm and 8.0 mm in combination of self-weight and earthquake load in X and Y direction, respectively. Moreover, the regions showing highest values of stress concentration are found through the small domes, through the openings of main dome and connections with arches, and around the openings of the walls.

Numerical Modelling of Moisture Loss during Controlled Drying of Marine Archaeological Wood

If left to dry uncontrollably following excavation, marine archaeological wood suffers significant and irreparable damage. Conservation treatments are required to consolidate degraded wood and to remove residual water. Drying must be controlled to eliminate erratic and heterogeneous water removal. Monitoring and understanding the drying process progression is invaluable information to garner real-time knowledge to correlate with chemical and physical material properties, and to develop future conservation strategies. Here, polyethylene glycol (PEG) consolidated marine archaeological wood was periodically sampled during drying to determine the moisture content as a function of location, time, and sample depth. The heterogeneous nature of the material leads to significant noise across spatial and temporal measurements, making it challenging to elucidate meaningful conclusions from visual observation of the raw data. Therefore, the spatiotemporal data was computationally analysed to produce a representative model of the ship’s drying, illustrated by a dynamic simulation. From this we can quantitatively predict the drying rate, determine the depth-dependence of drying, and estimate the resulting equilibrium moisture content. This is the first time such simulations have been carried out on this material and conservation process, demonstrating the power of applying numerical modelling to further our understanding of complex heritage data.

Characterization of a murine model of endothelial dysfunction induced by chronic intraperitoneal administration of angiotensin II

Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1β, IL17A, IL4, TGFβ, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.

Aspects of Multiscale Flow Simulation with Potential to Enhance Reservoir Engineering Practice

A new implementation of a multiscale sequential fully implicit (MS SFI) reservoir simulation method is applied to a set of reservoir engineering problems to understand its utility. An assessment is made to highlight areas where the approach brings substantial advantage in performance as well as address problems not successfully resolved by existing methods. This work makes use of the first ever implementation of the multiscale sequential fully implicit method in a commercial reservoir simulator. The key features of the method and implementation are briefly discussed. The learnings gained during field testing and commercialization on about forty real world models is illustrated through simpler, but representative data sets, available in the public domain. The workhorse robust fully implicit (FI) method is used as a reference for benchmarking. The MS SFI method can faithfully reproduce FI results for black oil problems. We conclude that the MS SFI method has the capability to support reservoir engineering decision making especially in the areas of subsurface uncertainty quantification, representative model selection, model calibration and optimization. The MS SFI method shows immense potential for handling prominent levels of reservoir heterogeneity. The challenge of including fine-scale heterogeneity, which is often overlooked, when scaling up EOR processes from laboratory to field, appears to have found a practical solution with a combination of MS SFI and high-performance computing (HPC).

Inhibiting ACSL1 related ferroptosis restrains MHV-A59 infection

Murine hepatitis virus strain A59 (MHV-A59) belongs to the β-coronavirus and is considered as a representative model for studying coronavirus infection. MHV-A59 was shown to induce pyroptosis, apoptosis and necroptosis of infected cells, especially the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59, is unknown. Here, we demonstrate inhibiting ferroptosis suppresses MHV-A59 infection. MHV-A59 infection upregulates the expression of Acsl1, a novel ferroptosis inducer. MHV-A59 upregulates Acsl1 expression depending on the NF-kB activation, which is TLR4-independent. Ferroptosis inhibitor inhibits viral propagation, inflammatory cytokines release and MHV-A59 infection induced cell syncytia formation. ACSL1 inhibitor Triacsin C suppresses MHV-A59 infection induced syncytia formation and viral propagation. In vivo administration of liproxstatin-1 ameliorates lung inflammation and tissue injuries caused by MHV-A59 infection. Collectively, these results indicate that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serves as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.

Escape from supercooling with or without bubbles: gravitational wave signatures

Quasi-conformal models are an appealing scenario that can offer naturally a strongly supercooled phase transition and a period of thermal inflation in the early Universe. A crucial aspect for the viability of these models is how the Universe escapes from the supercooled state. One possibility is that thermal inflation phase ends by nucleation and percolation of true vacuum bubbles. This route is not, however, always efficient. In such case another escape mechanism, based on the growth of quantum fluctuations of the scalar field that eventually destabilize the false vacuum, becomes relevant. We study both of these cases in detail in a simple yet representative model. We determine the duration of the thermal inflation, the curvature power spectrum generated for the scales that exit horizon during the thermal inflation, and the stochastic gravitational wave background from the phase transition. We show that these gravitational waves provide an observable signal from the thermal inflation in almost the entire parameter space of interest. Furthermore, the shape of the gravitational wave spectrum can be used to ascertain how the Universe escaped from supercooling.

Adaptation Mechanisms of Yak (Bos grunniens) to High-Altitude Environmental Stress

Living at a high altitude involves many environmental challenges. The combined effects of hypoxia and cold stress impose severe physiological challenges on endothermic animals. The yak is integral to the livelihood of the people occupying the vast, inhospitable Qinghai–Tibetan plateau and the surrounding mountainous region. Due to long-term selection, the yak exhibits stable and unique genetic characteristics which enable physiological, biochemical, and morphological adaptations to a high altitude. Thus, the yak is a representative model for mammalian plateau-adaptability studies. Understanding coping mechanisms provides unique insights into adaptive evolution, thus informing the breeding of domestic yaks. This review provides an overview of genetic adaptations in Bos grunniens to high-altitude environmental stress. Combined genomics and theoretical advances have informed the genetic basis of high-altitude adaptations.