Flow simulation-based particle swarm optimization for developing improved hemolysis models

The improvement and development of blood-contacting devices, such as mechanical circulatory support systems, is a life saving endeavor. These devices must be designed in such a way that they ensure the highest hemocompatibility. Therefore, in-silico trials (flow simulations) offer a quick and cost-effective way to analyze and optimize the hemocompatibility and performance of medical devices. In that regard, the prediction of blood trauma, such as hemolysis, is the key element to ensure the hemocompatibility of a device. But, despite decades of research related to numerical hemolysis models, their accuracy and reliability leaves much to be desired. This study proposes a novel optimization path, which is capable of improving existing models and aid in the development of future hemolysis models. First, flow simulations of three, turbulent blood flow test cases (capillary tube, FDA nozzle, FDA pump) were performed and hemolysis was numerically predicted by the widely-applied stress-based hemolysis models. Afterward, a multiple-objective particles swarm optimization (MOPSO) was performed to tie the physiological stresses of the simulated flow field to the measured hemolysis using an equivalent of over one million numerically determined hemolysis predictions. The results show that our optimization is capable of improving upon existing hemolysis models. However, it also unveils some deficiencies and limits of hemolysis prediction with stress-based models, which will need to be addressed in order to improve its reliability.

     

The influence of porosity on the hemocompatibility of polyhedral oligomeric silsesquioxane poly (caprolactone-urea) urethane

BackgroundThe physio-chemical properties of blood contacting biomaterials play an important role in determining their hemocompatibility. It is shown in literature that surface roughness and porosity have significant effect on hemocompatibility. In this study, we use a biocompatible, low thrombogenic nanocomposite polymer called POSS-PCU to test this hypothesis: would porosity compromise the hemocompatibility of POSS-PCU. We compared the hemocompatibility of POSS-PCU films of various pore sizes with PTFE, which is a commercially available material used in most blood contacting devices.MethodsSterilized POSS-PCU films with different size pores were prepared as samples and porous PTFE film were selected as control. And all samples were subjected to SEM for topograpgy, mechanical test for characterization and hemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the samples.ResultsWCA significantly increased with the pore size of POSS-PCU film, whereas both tensile stress and strain decreased significantly as the sizes of pores increased. However, when compared to PTFE film with same size pores, POSS-PCU films showed both higher tensile stress and strain. Pore size had little impact over POSS-PCU's surface chemistry groups as tested by FTIR analysis. Contact activation and platelet adhesion essay also showed no significant difference between different POSS-PCU samples. However, in whole blood reactions, POSS-PCU with pores size around 2–5 μm showed higher BCI than plain films and those with pores size around 35–45 μm. POSS-PCU showed lower thrombogencity and higher hemocompatibility comparing with porous PTFE on the aspects of platelet activation, adhesion and whole blood reaction.Summary and conclusionsPOSS-PCU polymer films as a biomaterial in chronic blood contacting implants show significant lower thrombogencity and higher hemocompatibility than porous PTFE film. It is desirable as a coating or covering material in small diameter stents for treating cardiovascular diseases, cerebral vascular diseases and peripheral arterial diseases.     

Flow-induced wall shear stress in abdominal aortic aneurysms: Part I--steady flow hemodynamics

Numerical predictions of blood flow patterns and hemodynamic stresses in Abdominal Aortic Aneurysms (AAAs) are performed in a two-aneurysm, axisymmetric, rigid wall model using the spectral element method. Homogeneous, Newtonian blood flow is simulated under steady conditions for the range of Reynolds numbers 10 < or =Re < or =2265. Flow hemodynamics are quantified by calculating the distributions of wall pressure (p(w)), wall shear stress (tau(w)), Wall Shear Stress Gradient (WSSG). A correlation between maximum values of hemodynamic stresses and Reynolds number is established, and the spatial distribution of WSSG is considered as a hemodynamic force that may cause damage to the arterial wall at an intermediate stage of AAA growth. The temporal distribution of hemodynamic stresses in pulsatile flow and their physical implications in AAA rupture are discussed in Part II of this paper.     

Layered Oxide Cathodes for Sodium‐Ion Batteries: Phase Transition,Air Stability,and Performance

The increasing demand for replacing conventional fossil fuels with clean energy or economical and sustainable energy storage drives better battery research today. Sodium‐ion batteries (SIBs) are considered as a promising alternative for grid‐scale storage applications due to their similar “rocking‐chair” sodium storage mechanism to lithium‐ion batteries, the natural abundance, and the low cost of Na resources. Searching for appropriate electrode materials with acceptable electrochemical performance is the key point for development of SIBs. Layered transition metal oxides represent one of the most fascinating electrode materials owing to their superior specific capacity, environmental benignity, and facile synthesis. However, three major challenges (irreversible phase transition, storage instability, and insufficient battery performance) are known for cathodes in SIBs. Herein, a comprehensive review on the latest advances and progresses in the exploration of layered oxides for SIBs is presented, and a detailed and deep understanding of the relationship of phase transition, air stability, and electrochemical performance in layered oxide cathodes is provided in terms of refining the structure–function–property relationship to design improved battery materials. Layered oxides will be a competitive and attractive choice as cathodes for SIBs in next‐generation energy storage devices.     

A numerical study on hemodynamics in the left coronary bifurcation with normal and hypertension conditions

In this study, a three-dimensional analysis of the non-Newtonian blood flow was carried out in the left coronary bifurcation. The Casson model and hyperelastic and rigid models were used as the constitutive equation for blood flow and vessel wall model, respectively. Physiological conditions were considered first normal and then compliant with hypertension disease with the aim of evaluating hemodynamic parameters and a better understanding of the onset and progression of atherosclerosis plaques in the coronary artery bifurcation. Two-way fluid–structure interaction method applying a fully implicit second-order backward Euler differencing scheme has been used which is performed in the commercial code ANSYS and ANSYS CFX (version 15.0). When artery deformations and blood pressure are associated, arbitrary Lagrangian–Eulerian formulation is employed to calculate the artery domain response using the temporal blood response. As a result of bifurcation, noticeable velocity reduction and backflow formation decrease shear stress and made it oscillatory at the starting point of the LCx branch which caused the shear stress to be less than 1 and 2 Pa in the LCx and the LAD branches, respectively. Oscillatory shear index (OSI) as a hemodynamic parameter represents the increase in residence time and oscillatory wall shear stress. Because of using the ideal 3D geometry and realistic physiological conditions, the values obtained for shear stress are more accurate than the previous studies. Comparing the results of this study with previous clinical investigations shows that the regions with low wall shear stress less than 1.20 Pa and with high OSI value more than 0.3 are in more potential risk to the atherosclerosis plaque development, especially in the posterior after the bifurcation.     

Application of Plasmonics in Solar Cell Efficiency Improvement: a Brief Review on Recent Progress

We need electrical energy for our various daily life activities, and the existing fossil fuel will serve the purpose for a limited period only. Therefore, we need to look at alternate energy resources for long-term sustainable growth. Solar energy has been considered as one of the potential viable alternate sources of non-conventional energy. Solar photon harvesting is a technique where solar photon energy is being converted to electrical energy using solar cell devices. However, the solar power conversion efficiency is usually seen to be poor limiting the applications to large extent. Improving solar cell efficiency has, thus, been a great challenge to researchers who are actively working in this field. Various technological aspects are being looked at to improve efficiency, and out of them, plasmonic light trapping technique has been considered as one of the promising techniques. In the past years, considerable research efforts are being made towards the design and execution of the solar cell devices and to understand the mechanisms of performance enhancement. The present review outlines briefly the recent progress of plasmonic solar cell efficiency improvement that has happened, especially, for last 5–6 years. Plasmonic solar cells made of Si (silicon), GaAs (gallium arsenide); plasmonic dye-sensitized solar cells; plasmonic polymer (organic) solar cells and perovskite solar cells are mainly discussed along with the critical aspects that may influence the device performance.

     

New heat shock protein (Hsp90) inhibitors,designed by pharmacophore modeling and virtual screening: synthesis,biological evaluation and molecular dynamics studies

Abstract

Inhibition of heat shock protein 90 (Hsp90) is known to be a significantly effective strategy in cancer therapy. Here, pyrazolopyranopyrimidine derivatives were characterized as new Hsp90 inhibitors. The molecules’ key structure (ZINC02819805) was determined by utilizing a pharmacophore model virtual screening workflow. Structural optimization was then carried out on compound ZINC02819805, pyrazolopyranopyrimidine derivatives were designed and six chosen derivatives were synthesized. The inhibition of Hsp90 ATPase activity of synthesized compounds revealed that para methylphenyl derivative of pyrazolopyranopyrimidine (HM3) was the most potent inhibitor (IC₅₀ = 5.5?µM). The anti-proliferative activity of this compound was evaluated against a panel of cell lines including MCF-7, HeLa and HUVEC (IC₅₀ = 1.28?µM, IC₅₀ = 1.74?µM and IC₅₀ = 61.48?µM respectively) by MTT method. The western blot analysis of treated MCF-7 cells with compound HM3 showed that the expression level of Hsp70 and Her2 proteins changed. The high level of Hsp70 expression and low level of Her2 expression suggest that compound HM3 exhibits inhibitory effect on Hsp90. Finally, the key interactions between HM3 and Hsp90 protein were studied by molecular dynamics simulation and showed that compound HM3 was stable in Hsp90 active cite during 200?ns simulation. Abbreviations Hsp90 Heat shock protein 90

MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

ATP adenosine triphosphate

MD molecular dynamics simulation

RMSD root-mean-square deviation

RMSF root-mean-square fluctuation

Rg gyration radius

m-SABNPs boehmite nanoparticles-supported sulfamic acid

Communicated by Ramaswamy H. Sarma     

Comparison of the in vitro hemodynamic performance of new flow diverters for bypass of brain aneurysms

One possible treatment for cerebral aneurysms is a porous tubular structure, similar to a stent, called a flow diverter. A flow diverter can be placed across the neck of a cerebral aneurysm to induce the cessation of flow and initiate the formation of an intra-aneurysmal thrombus. This excludes the aneurysm from the parent artery and returns the flow of blood to normal. Previous flow diverting devices have been analyzed to determine optimal characteristics, such as braiding angle and wire diameter. From this information, a new optimized device was designed to achieve equivalent hemodynamic performance to the previous best device, but with better longitudinal flexibility to preserve physiological arterial configuration. The new device was tested in vitro in an elastomeric replica of the rabbit elastase induced aneurysm model and is now in the process of being tested in vivo. Particle image velocimetry was utilized to determine the velocity field in the plane of symmetry of the model under pulsatile flow conditions. Device hemodynamic performance indices such as the hydrodynamic circulation were evaluated from the velocity fields. Comparison of these indices with the previous best device and a control shows that the significant design changes of the device did not change its hemodynamic attributes (p?>?0.05).     

Amyloid precursor protein-mediated free radicals and oxidative damage: implications for the development and progression of Alzheimer's disease

Alzheimer's disease (AD) is a late-onset dementia that is characterized by the loss of memory and an impairment of multiple cognitive functions. Advancements in molecular, cellular, and animal model studies have revealed that the formation of amyloid beta (Abeta) and other derivatives of the amyloid precursor protein (APP) are key factors in cellular changes in the AD brain, including the generation of free radicals, oxidative damage, and inflammation. Recent molecular, cellular, and gene expression studies have revealed that Abeta enters mitochondria, induces the generation of free radicals, and leads to oxidative damage in post-mortem brain neurons from AD patients and in brain neurons from cell models and transgenic mouse models of AD. In the last three decades, tremendous progress has been made in mitochondrial research and has provided significant findings to link mitochondrial oxidative damage and neurodegenerative diseases such as AD. Researchers in the AD field are beginning to recognize the possible involvement of a mutant APP and its derivatives in causing mitochondrial oxidative damage in AD. This article summarizes the latest research findings on the generation of free radicals in mitochondria and provides a possible model that links Abeta proteins, the generation of free radicals, and oxidative damage in AD development and progression.     

A novel formulation for blood trauma prediction by a modified power-law mathematical model

With the increasing use of artificial organs, blood damage has been raising ever more clinical concern. Blood trauma is in fact a major complication resulting from the implantation of medical devices and the use of life support apparatuses. Red blood cells damage predictive models furnish critical information on both the design and the evaluation of artificial organs, because their correct usage and implementation are thought to provide clear and rational guidance for the improvement of safety and efficacy. The currently adopted power-law shear-induced haemolysis prediction model lacks sensitivity with respect to the cumulative effect of previously applied stress magnitudes. An alternative model is proposed where a mechanical quantity was defined, able to describe the blood damage sustained by red cells under unsteady stress conditions, taking into account the load history. The proposed formulation predicted the same trend as the available experimental data. The obtained results have to be considered a preliminary validation of the basic hypothesis of this modified red blood cell damage prediction model. To date, the necessity to design further experiments to validate the proposed damage function clashes with the limitations inherent to current systems to get the time-varying shear stress completely under control.     

Bacteriophages of Clostridium saccharoperbutylacetonicum

The fine structure of phage HM 2 (group I) active on Clostridium saccharoperbutylacetonicum was studied by an electron microscopy with a negative-staining technique, and compared with those of more conventional types, phages HM 3 (group II) and HM 7 (group III), whose tails were clearly observed by a shadow-casting technique. This study revealed that phage HM 2 had an intricate tail which was not observed by a shadow-casting technique.

Phage HM 2 has an icosahedral head about 450 Å in diameter and a non-contractile tail about 300 Å long. The distal 130 Å of the tail axis has a width of 80 Å which is wider than the upper portion of the tail (50 to 60 Å). The distal enlargement is not seen in the hollow tail. Twelve fibrous-shaped appendages are attached symmetrically at the upper portion of tail axis and extend toward the distal base of the tail. Their length is a little shorter than 300 Å. They combine with divalent cations in the phage dilution medium, and also adsorb the host cell debris.

Phage HM 3 has an icosahedral head about 770 Å in diameter and a tail about 1000 Å long and 150 Å wide with contractile sheath. Phage HM 7 has an icosahedral head about 750 Å in diameter and a long non-contractile tail about 2000 Å long and about 120 Å wide with forked tip.

The structure of the tail of phage HM 2 is quite different from those of phages HM 3 and HM 7 hitherto described and those of the various phages of other bacteria.     

A computational thrombus formation model: application to an idealized two-dimensional aneurysm treated with bare metal coils

Cardiovascular implantable devices alter the biofluid dynamics and biochemistry of the blood in which they are placed. These perturbations can lead to thrombus formation which may or may not be desired, depending on the application. In this work, a computational model is developed that couples biofluid dynamics and biochemistry to predict the clotting response of blood to such devices. The model consists of 28 advection–diffusion–reaction partial differential equations to track proteins in the blood involved in clotting and utilizes boundary flux terms to model the initiation of the intrinsic clotting pathway at thrombogenic device surfaces. We use this model to simulate the transient clot growth within a 2D idealized bifurcation aneurysm filled with various distributions of bare metal coils with similar packing densities. The clot model predicts initial clot formation to occur in areas along coil surfaces where flow is minimal and where time-averaged shear rates are the smallest. Among the six coil-filled aneurysm cases simulated, maximum thrombus occlusion ranged between 80.8 and 92.2% of the post-treatment aneurysm volume and was achieved 325–450 s after treatment. With further refinement and validation, the computational clotting model will be a valuable engineering tool for evaluating and comparing the relative performance of cardiovascular implantable devices.     

Biochemical markers for clinical monitoring of tissue perfusion

The assessment and monitoring of the tissue perfusion is extremely important in critical conditions involving circulatory shock. There is a wide range of established methods for the assessment of cardiac output as a surrogate of oxygen delivery to the peripheral tissues. However, the evaluation of whether particular oxygen delivery is sufficient to ensure cellular metabolic demands is more challenging. In recent years, specific biochemical parameters have been described to indicate the status between tissue oxygen demands and supply. In this review, the authors summarize the application of some of these biochemical markers, including mixed venous oxygen saturation (S_vO₂), lactate, central venous–arterial carbon dioxide difference (PCO₂ gap), and PCO₂ gap/central arterial-to-venous oxygen difference (C_a–vO₂) for hemodynamic assessment of tissue perfusion. The thorough monitoring of the adequacy of tissue perfusion and oxygen supply in critical conditions is essential for the selection of the most appropriate therapeutic strategy and it is associated with improved clinical outcomes.

     

冬眠哺乳动物氧化应激产生及抗氧化防御机制研究进展

哺乳动物的冬眠是一种季节性异温状态,是对外界恶劣自然环境的一种适应策略。冬眠-阵间觉醒周期中,伴随着生理功能的剧烈变化,从冬眠期间整体代谢的抑制,到阵间觉醒时氧代谢的急剧增加,使动物体内产生了大量的氧自由基。然而,冬眠动物出眠时并未表现出明显的氧化损伤迹象,因此,冬眠哺乳动物被认为是一种天然的抗氧化损伤模型。本文从氧化应激的产生、活性氧的来源、抗氧化防御等方面综述了冬眠哺乳动物对氧化应激的防御,并从其抗氧化的分子调控方面分析了冬眠哺乳动物对氧化应激的适应机制。     

Current and historical patterns of heavy metals pollution in Estonia as reflected in natural media of different ages: ICP Vegetation,ICP Forests and ICP Integrated Monitoring data

In order to characterise current and historical pattern of heavy metal (HM) pollution in Estonia, this article will compare the concentrations and stocks of Cd, Cr, Cu, Ni, Pb and Zn represented in current deposition (data from 18 local precipitation stations) with natural media of three different ages: 1–3-year-old moss carpet (ICP Vegetation moss survey data from 99 open area plots), 3–5-year-old litter layer, and several-decades-old organic layer (mor humus) of coniferous forest, in mostly podzolic soils (ICP Forest soil survey data, 75 stands).Objectives of this study are (1) to assess differences in HM retention and accumulation in various aged media of coniferous stands (2) to estimate territorial differences in current HM distribution and previously accumulated concentrations and stores of HM (3) to compare territorial distribution of HM concentration in Estonia between five different regions: N-W; N-E; S-W; S-E and Western insular region, whereas the local oil shale industry in N-E part of Estonia has been the main source of HM pollution over a long period of time and therefore may have an effect on HM regional distribution.Comparing the studied media, three types of HM retention patterns were detected: (1) for Cu, Ni, Cr (2) for Cd, Pb, (3) for Zn. The mean current level of HM deposition in Estonia is low comparison to previous decades, especially the 1980s. The effect of the previously significantly higher exposure of HM emissions and deposition is preserved in older part of soil organics (OF), where the highest stocks and concentrations of HMs (with the exception of Zn) are currently found. The HM proportions in fly ash of oil shale and in OF layer of soil were very similar with regards to Ni and Cr—indicating their origin from the oil shale industry in the N-E region. According to spatial distribution analysis, the greatest accumulated storages of Ni and Cr in OF layer of coniferous forest soils are characteristic to S-W Estonia.     

Influence of novel naphthalimide-based organoselenium on genotoxicity induced by an alkylating agent: the role of reactive oxygen species and selenoenzymes

Abstract

Objective

The protection conferred by a series of synthetic organoselenium compounds against genotoxicity and oxidative stress induced by a reference mutagen cyclophosphamide (CP) was assessed.

Method

Genotoxicity was induced in mice by CP treatment (25 mg/kg b.w.) for 10 consecutive days. Organoselenium compounds (3 mg/kg b.w.) were administered orally in a concomitant and pretreatment schedule. DNA damage in peripheral blood lymphocytes and frequency of chromosomal aberration in the bone marrow cells were measured. Liver tissues were collected for analysis of the activity of antioxidant and detoxifying enzymes, lipid peroxidation (LPO) level, glutathione content, and histopathology.

Results

Exposure to CP not only led to a significant increase in the percent of chromosomal aberration and DNA damage, but also enhanced generation of hepatic reactive oxygen species (ROS) and LPO level. The organoselenium compounds demonstrated marked functional protection against CP-induced genotoxicity. DNA damage and chromosomal aberration along with ROS generation were attenuated in the organoselenium-treated mice compared with the CP-treated control mice. CP caused marked depression in the activities of the selenoenzymes (glutathione peroxidase (GPx) and thioredoxin reductase (TRxR)) and other detoxifying and antioxidant enzymes, while treatment with organoselenium compounds restored all these activities towards normal.

Discussion

The protective effect of these compounds may be primarily associated with the improvement of the activity of antioxidant and detoxifying enzymes (including the selenoenzymes, GPx, and TRxR) that are known to protect the DNA and other cellular components from oxidative damage.     

Nanofiber‐Based Bulk‐Heterojunction Organic Solar Cells Using Coaxial Electrospinning

Nanofibers consisting of the bulk heterojunction organic photovoltaic (BHJ–OPV) electron donor–electron acceptor pair poly(3‐hexylthiophene):phenyl‐C₆₁‐butyric acid methyl ester (P3HT:PCBM) are produced through a coaxial electrospinning process. While P3HT:PCBM blends are not directly electrospinnable, P3HT:PCBM‐containing fibers are produced in a coaxial fashion by utilizing polycaprolactone (PCL) as an electrospinnable sheath material. Pure P3HT:PCBM fibers are easily obtained after electrospinning by selectively removing the PCL sheath with cyclopentanone (average diameter 120 ± 30 nm). These fibers are then incorporated into the active layer of a BHJ–OPV device, which results in improved short‐circuit current densities, fill factors, and power‐conversion efficiencies (PCE) as compared to thin‐film devices of identical chemical composition. The best‐performing fiber‐based devices exhibit a PCE of 4.0%, while the best thin‐film devices have a PCE of 3.2%. This increase in device performance is attributed to the increased in‐plane alignment of P3HT polymer chains on the nanoscale, caused by the electrospun fibers, which leads to increased optical absorption and subsequent exciton generation. This methodology for improving device performance of BHJ–OPVs could also be implemented for other electron donor–electron acceptor systems, as nanofiber formation is largely independent of the PV material.     

Identification and comparison of stochastic metabolic/hemodynamic models (sMHM) for the generation of the BOLD signal

This paper extends a previously formulated deterministic metabolic/hemodynamic model for the generation of blood oxygenated level dependent (BOLD) responses to include both physiological and observation stochastic components (sMHM). This adds a degree of flexibility when fitting the model to actual data by accounting for un-modelled activity. We then show how the innovation method can be used to estimate unobserved metabolic/hemodynamic as well as vascular variables of the sMHM, from simulated and actual BOLD data. The proposed estimation method allowed for doing model comparison by calculating the model’s AIC and BIC. This methodology was then used to select between different neurovascular coupling assumptions underlying sMHM. The proposed framework was first validated on simulations and then applied to BOLD data from a motor task experiment. The models under comparison in the analysis of the actual data considered that vascular response was coupled to: (I) inhibition, (II) excitation, (III) both excitation and inhibition. Data was best described by model II, although model III was also supported.     

Bacteriophages of Clostridium saccharoperbutylacetonicum

The three representative HM-phages (HM 2, HM 3 and HM 7) of Clostridium saccharoperbutylacetonicum were used.

The adsorption rate of the phages HM 2 and HM 7 on the host bacteria was high, whereas that of the phage HM 3 was lower. The adsorption rates of the phages were maximum at pH 5.9~6.6, 30°C.

One-step growth experiment was successfully adapted to the phage-host systems of anaerobic bacteria by bubbling pure nitrogen gas into the medium in the growth tube. The growth characteristics of the HM-phages were investigated by using this technique. The minimal latent periods for phages HM 2, HM 3 and HM 7 were about 45, 90 and 120 minutes, respectively. The corresponding average burst sizes were approximately 500, 100 and 20, respectively. The growth of the phages was optimal at pH 6.2, 30~33°C. The phages failed to grow at 37°C, although the host bacteria multiplied at that temperature. By using a defined medium, it was found that calcium ion was not essential for the growth of the HM-phages.