•Flow and heat transfer characteristics of the turbulent flow in the tube have been investigated.•We investigate the effect of attack angle of ribs and Al2O3 nanoparticle on the heat transfer ...enhancement.•The flow has been simulated in Reynolds numbers of 24000, 36000, 48000 and 60000.
In present research, the flow and heat transfer characteristics of the turbulent flow in the tube have been numerically investigated. The main purpose of this study is investigating the effect of attack angle of ribs and Al2O3 nanoparticle on the heat transfer enhancement. The flow has been simulated in Reynolds numbers of 24000, 36000, 48000 and 60000 in volume fractions of 0, 2 and 4% of nanoparticles. In present study, in order to ensure from the accuracy of numerical solving procedure, the obtained results have been compared with others empirical and numerical results and proper coincidence has been obtained. The mean Nusselt number, pressure drop and performance coefficient are presented results. In addition to the mentioned quantitative results, in order to investigate of physics of flow, the stream lines, are also presented. The obtained results demonstrate that, the existence of ribs with the creation of eddy on the direction of flow causes better mixture of flow and consequently, heat transfer increases and adding nanoparticles to the base flow causes more augment of heat transfer. According to the obtained results, in order to improve the heat transfer without considering the applied pressure drop, using rib with angle of attack 90° inside the tube is suggested. However, the investigation of fluid- thermal performance coefficient indicates that, the ratio of heat transfer enhancement to the applied pressure drop in the rib with attack angle of 60° is maximum.
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Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and ...lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.
Asthma is a chronic and genetically complex respiratory disease that affects over 300 million people worldwide. Here, we report a genome-wide analysis for asthma using data from the UK Biobank and ...the Trans-National Asthma Genetic Consortium. We identify 66 previously unknown asthma loci and demonstrate that the susceptibility alleles in these regions are, either individually or as a function of cumulative genetic burden, associated with risk to a greater extent in men than women. Bioinformatics analyses prioritize candidate causal genes at 52 loci, including CD52, and demonstrate that asthma-associated variants are enriched in regions of open chromatin in immune cells. Lastly, we show that a murine anti-CD52 antibody mimics the immune cell-depleting effects of a clinically used human anti-CD52 antibody and reduces allergen-induced airway hyperreactivity in mice. These results further elucidate the genetic architecture of asthma and provide important insight into the immunological and sex-specific relevance of asthma-associated risk variants.
•This paper investigates the molecular dynamics behavior of argon Poiseuille flow in copper nanochannels.•This study explores the combined existence of obstacles on the surface and in the regions ...above the surface of the nanochannel wall.•The aim is to examine the velocity, density, and temperature fields, as well as the heat flux and thermal conductivity coefficient, by utilizing the LAMMPS software.•The number density of argon atoms displays relatively intense fluctuations when obstacles are present near the nanochannel walls.•The maximum heat transfer, compared to a smooth nanochannel, reaches 72 percent, which occurs with an increase in the number of obstacles in the nanochannel.
This study investigates the molecular dynamics behavior of argon Poiseuille flow in copper nanochannels with two-dimensional geometry (with two solid walls) and three-dimensional geometry (with four solid walls) utilizing the LAMMPS software. This study explores the combined existence of obstacles on the surface (with index R) and in the regions above the surface of the nanochannel wall (with index P) at varying numbers, along with applying an external force in the flow direction. The aim is to examine the velocity, density, and temperature fields, as well as the heat flux and thermal conductivity coefficient for 10,000 time steps, using the hybrid Lennard-Jones Embedded Atom Method (EAM) potential function. The findings of this study suggest that alterations in wall and fluid temperature, the impact of wall force, and the existence of obstacles have noteworthy impacts on flow parameter behavior. The fluctuations in fluid temperature, density, velocity, and thermal conductivity coefficient are influenced by modifications in the kinetic behavior of flowing atoms resulting from the collision and atomic diffusion mechanism. The number density of argon atoms displays relatively intense fluctuations when obstacles are present near the nanochannel walls. However, the fluctuations are comparatively lower compared to the case without obstacles. Conversely, placing an obstacle inside an ideal nanochannel reduces the amplitude of fluid atoms' motion fluctuations in the proximity of the walls. Compared to a smooth nanochannel, the maximum heat transfer reaches 72 percent, which occurs with an increase in the number of obstacles in the nanochannel. In conclusion, the presence of P-structured obstacles in the two-dimensional nanochannel leads to a 2.8-fold surge in the thermal conductivity coefficient compared to a smooth nanochannel of the external force.
Summary
Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in ...immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti‐helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co‐stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease.
Autophagy maintains homeostasis and is induced upon stress. Yet, its mechanistic interaction with oncogenic signaling remains elusive. Here, we show that in BRAF
-melanoma, autophagy is induced by ...BRAF inhibitor (BRAFi), as part of a transcriptional program coordinating lysosome biogenesis/function, mediated by the TFEB transcription factor. TFEB is phosphorylated and thus inactivated by BRAF
via its downstream ERK independently of mTORC1. BRAFi disrupts TFEB phosphorylation, allowing its nuclear translocation, which is synergized by increased phosphorylation/inactivation of the ZKSCAN3 transcriptional repressor by JNK2/p38-MAPK. Blockade of BRAFi-induced transcriptional activation of autophagy-lysosomal function in melanoma xenografts causes enhanced tumor progression, EMT-transdifferentiation, metastatic dissemination, and chemoresistance, which is associated with elevated TGF-β levels and enhanced TGF-β signaling. Inhibition of TGF-β signaling restores tumor differentiation and drug responsiveness in melanoma cells. Thus, the "BRAF-TFEB-autophagy-lysosome" axis represents an intrinsic regulatory pathway in BRAF-mutant melanoma, coupling BRAF signaling with TGF-β signaling to drive tumor progression and chemoresistance.
Thomson heat absorption corresponding to changes in the Seebeck coefficient with respect to temperature enables the design of thermoelectric coolers wherein Thomson cooling is the dominant term, ...i.e., the Thomson coolers. Thomson coolers extend the working range of Peltier coolers to larger temperature differences and higher electrical currents. The Thomson coefficient is small in most materials. Recently, large Thomson coefficient values have been measured attributed to thermally induced phase change during magnetic and structural phase transitions. The large Thomson coefficient observed can result in the design of highly efficient Thomson coolers. This work analyzes the performance of Thomson coolers analytically and sets the metrics for evaluating the performance of materials as their constituent components. The maximum heat flux when the Thomson coefficient is constant is obtained and the performance is compared to Peltier coolers. Three dimensionless parameters are introduced which determine the performance of the Thomson coolers and can be used to analyze the coefficient of performance, the maximum heat flux, and the maximum temperature difference of a Thomson cooler.
Role of Autophagy in Lung Inflammation Painter, Jacob D; Galle-Treger, Lauriane; Akbari, Omid
Frontiers in immunology,
07/2020, Volume:
11
Journal Article
Peer reviewed
Open access
Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes ...for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a T
17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between T
2 and T
17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.
In the present study, heat transfer and laminar flow of a nanofluid in a vertical channel by considering the effect of radiation with single- and two-phase approaches with prescribed surface ...temperature conditions and prescribed surface heat flux conditions were simulated. The main goal of this study is to investigate the effect of variations of Grashof number (
Gr
), radiation parameter (
Nr
) and volume fraction of nanoparticles (
ϕ
) on flow and heat transfer characteristics. For this goal, flow with
Gr
= 5, 10, 15 and 20, volume fractions of 0, 0.1 and 0.2 and radiation parameters of
Nr
= 0, 0.5 and 1 were simulated. The results show that by increasing Grashof number in both cases of constant heat flux and temperature, nanofluid velocity increases and in both cases of constant temperature and heat flux by increasing volume fraction, the velocity and temperature of the nanofluid drops. The presence of moving wall (plate boundary condition) induces secondary flows in the flow field, and the flow movement in the channel will experience drift because of temperature variations and buoyancy forces due to inducement of secondary forces and the effect of penetration of moving plate velocity into the fluid close by it which will affect the entire fluid flow field in the end. For fixed plate case, the velocity of nanofluid at the walls is zero because of fixed position of the plate and presence of no-slip boundary condition on the solid walls. By increasing the applied temperature, the value of kinetic and internal energy of the velocity field rises which results in higher density gradients and higher buoyancy forces. For both constant heat flux and temperature, increasing solid nanoparticles volume fraction results in lowering of the velocity contour elevations. The quantitative level of axial velocity curves for constant heat flux condition compared with constant temperature case for
Gr
= 5 and
Nr
= 0.5 is about 2–3 times less. For constant temperature boundary condition, for
Gr
= 5 and
Nr
= 0.5 and volume fraction of 0.1%, the maximum velocity happens at regions 30–50% of channel height from the bottom.
In this brief, a low energy consumption block-based carry speculative approximate adder is proposed. Its structure is based on partitioning the adder into some non-overlapped summation blocks whose ...structures may be selected from both the carry propagate and parallel-prefix adders. Here, the carry output of each block is speculated based on the input operands of the block itself and those of the next block. In this adder, the length of the carry chain is reduced to two blocks (worst case), where in most cases only one block is employed to calculate the carry output leading to a lower average delay. In addition, to increase the accuracy and reduce the output error rate, an error detection and recovery mechanism is proposed. The effectiveness of the proposed approximate adder is compared with state-of-the-art approximate adders using a cost function based on the energy, delay, area, and output quality. The results indicate an average of 50% reduction in terms of the cost function compared to other approximate adders.
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