When a fluid-filled cube rotating rapidly about an axis passing through two opposite vertices is subjected to harmonic modulations of its rotation rate (librations) at a modulation frequency that is $2/\sqrt {3}$ times the mean rotation frequency, all walls of the cube have critical reflection slopes. As such, all inertial wave beams emitted from edges and vertices of the cube in response to the librations are trapped in thin oscillatory boundary layers for forcing amplitudes (Rossby numbers) below a critical value which depends on the Ekman number (ratio of rotation to viscous time scales). How the resulting oscillatory boundary layer flow, referred to as a boundary-confined wave, depends on Ekman and Rossby numbers is examined in detail over several decades. Of particular interest is how the mean flow grows with increasing forcing amplitude, leading to instability resulting from nonlinear interactions between the mean flow and waves in the oscillatory boundary layers, injecting intense small-scale structures throughout the cube.

A fluid-filled cube rotating about an axis passing through the midpoints of opposite edges is subjected to small librations (i.e. modulation of the mean rotation). Low viscosity regimes, with Ekman number as small as $10^{-8}$ and equally small relative forcing amplitude, are explored numerically. The full inertial range of forcing frequencies, from 0 to twice the mean rotation rate are considered. The response flows are dominated by inertial wavebeams emitted from edges and/or vertices, depending on the forcing frequency. How these reflect on the cube's walls and focus onto edges and vertices lead to intricate patterns. Most of the results can be reconciled using linear inviscid ray-tracing theory with careful attention to wavebeam emissions and reflections. However, even at the low Ekman number and relative forcing amplitude considered, other effects are discernible which are not captured by ray tracing. These include a symmetry breaking due to viscous effects and a progressive wave, retrograde to the mean rotation and localized in the boundary layers of the cube, due to nonlinear effects and the librational forcing.

OBJECTIVES/GOALS: The SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2), which underlies the current COVID-19 pandemic, among other tissues, also targets the central nervous system (CNS). The goal of this study is to investigate mechanisms of neuroinflammation in Lipopolysaccharides (LPS)-treated mouse model and SARS-CoV-2-infected hamsters. METHODS/STUDY POPULATION: In this research I will assay vascular reactivity of cerebral vessels to assess vascular dysfunction within the microcirculation. I will determine expression of proinflammatory cytokines, coagulation factors and AT1 receptors (AT1R) in isolated microvessels from the circle of Willis to assess inflammation, thrombosis and RAS activity in the microvasculature. LPS and SARS-CoV-2, are both associated with coagulopathies and because of that I will measure concentration of PAI-1, von Willebrand Factor, thrombin and D-dimer to assess the thrombotic pathway in the circulation. Histology and immunohistochemistry will assess immune cell type infiltration into the brain parenchyma, microglia activation and severity of neuroinflammation and neural injury. RESULTS/ANTICIPATED RESULTS: We hypothesize that under conditions of reduced ACE2 (e.g., SARS-CoV-2 infection), AT1R activity is upregulated in the microvasculature. In the presence of an inflammatory insult, these AT1Rs promote endothelialitis and immunothrombosis through pro-thrombotic pathways and pro-inflammatory cytokine production leading to endothelial dysfunction in the microvasculature, blood brain barrier (BBB) injury, deficits in cognition and increased anxiety. We will test this hypothesis through 2 aims: Aim 1: Determine the role of the pro-injury arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. Aim 1: Determine the role of the protective arm of the RAS in the pathophysiology of the brain in animal models of neuroinflammation and COVID-19. DISCUSSION/SIGNIFICANCE: This study will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19. This research is a necessary first step in understanding mechanisms of brain pathogenesis that can set the groundwork for future studies of more complex models of disease.

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82–39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively.

We study the effect of algorithmic trading (AT) on market quality between 2001 and 2011 in 42 equity markets around the world. We use an exchange colocation service that increases AT as an exogenous instrument to draw causal inferences about AT on market quality. On average, AT improves liquidity and informational efficiency but increases short-term volatility. Importantly, AT also lowers execution shortfalls for buy-side institutional investors. Our results are surprisingly consistent across markets and thus across a wide range of AT environments. We further document that the beneficial effect of AT is stronger in large stocks than in small stocks.

Toxoplasma gondii rhoptry protein TgROP18 is a polymorphic virulence effector that targets immunity-related GTPases (IRGs) in rodents. Given that IRGs are uniquely diversified in rodents and not in other T. gondii intermediate hosts, the role of TgROP18 in manipulating non-rodent cells is unclear. Here we show that in human cells TgROP18I interacts with the interferon-gamma-inducible protein N-myc and STAT interactor (NMI) and that this is a property that is unique to the type I TgROP18 allele. Specifically, when expressed ectopically in mammalian cells only TgROP18I co-immunoprecipitates with NMI in IFN-γ-treated cells, while TgROP18II does not. In parasites expressing TgROP18I or TgROP18II, NMI only co-immunoprecipitates with TgROP18I and this is associated with allele-specific immunolocalization of NMI on the parasitophorous vacuolar membrane (PVM). We also found that TgROP18I reduces NMI association with IFN-γ-activated sequences (GAS) in the IRF1 gene promoter. Finally, we determined that polymorphisms in the C-terminal kinase domain of TgROP18I are required for allele-specific effects on NMI. Together, these data further define new host pathway targeted by TgROP18I and provide the first function driven by allelic differences in the highly polymorphic ROP18 locus.

The response to librational forcing of a cube in rapid rotation about a diagonal axis is explored. In this orientation, the faces of the cube are all oblique to the rotation axis. The system supports inertial waves, which predominantly comprise beams emitted from the edges and vertices of the cube. Which ones emit and the resulting complicated pattern of three-dimensional reflections and subsequent focusing depend on the libration frequency. Direct numerical simulations of the Navier–Stokes flows with no-slip boundary conditions at low Ekman number ($\text{E}=10^{-7}$) and small libration amplitude ($\unicode[STIX]{x1D716}=10^{-7}$) exhibit complicated spatio-temporal structure that is remarkably well described by considerations of the inviscid reflections of wavebeams over the whole range of libration frequencies from zero to twice the mean rotation rate of the cube.

This work demonstrates a double-step method, a simple chemical bath deposition and an in situ polymerization process, to synthesize the stable structure of a composite of Polyaniline/BiVO4/cellulose aerogel (PBC) in wastewater treatment. The poor stability of the carrier catalyst was improved significantly by forming a dense film of polyaniline (PANI) through polymerization on BiVO4/cellulose aerogel (BC). The developed three-dimensional porous structure enhanced photocatalytic stability. For instance, photocatalytic degradation of a dye, methylene blue, reached to 91.67% under the eight times successive irradiation of the visible light. The resulted fine performance could be owed to the strong adsorption of cellulose aerogel, uniform spreading of BiVO4, and the speedy electron separation efficiency of PBC. Moreover, the photocatalytic mechanisms including the role of the free radicals (•OH and •O2−) of the developed PBC were also discussed. The novel structure may present a new insight into the development of the carrier catalyst.

Numerical simulations of the response flow in a fluid-filled rotating cube that is subjected to precessional forcing are examined over a wide range of rotation, precession and forcing frequencies. The responses are shown to correspond to resonantly excited inertial modes of the rotating cube that have the same spatio-temporal symmetry as the precessional forcing and, under certain conditions, the response flow loses stability via symmetry breaking that is intricately associated with a triadic resonance between the forced flow and two free inertial modes whose spatio-temporal symmetries do not coincide with that of the precessional forcing.

The experiment was conducted to investigate the effects of dietary threonine (Thr) on growth performance and muscle growth, protein synthesis and antioxidant-related signalling pathways of hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. A total of 1200 fish (14·19 (se 0·13) g) were randomly distributed into six groups with four replicates each, fed six diets with graded level of Thr (9·5, 11·5, 13·5, 15·4, 17·4 and 19·3 g/kg diets) for 56 d. Results showed (P < 0·05) that dietary Thr (1) increased percentage weight gain, specific growth rate, feed efficiency and protein efficiency ratio; (2) up-regulated growth hormone (GH), insulin-like growth factor 1 (IGF-1), proliferating cell nuclear antigen, myogenic regulation factors (MyoD, Myf5, MyoG and Mrf4) and myosin heavy chain (MyHC) mRNA levels; (3) increased muscle protein content via regulating the protein kinase B/target of rapamycin signalling pathway and (4) decreased malondialdehyde and protein carbonyl contents, increased catalase, glutathione-S-transferase, glutathione reductase and GSH activities, up-regulated mRNA levels of antioxidant enzymes related to NFE2-related factor 2 and γ-glutamylcysteine ligase catalytic subunit. These results suggest that Thr has a potential role to improve muscle growth and protein synthesis, which might be due to the regulation of GH-IGF system, muscle growth-related gene, antioxidative capacity and protein synthesis-related signalling pathways. Based on the quadratic regression analysis of specific growth rate, the Thr requirement of hybrid catfish (14·19–25·77 g) was estimated to be 13·77 g/kg of the diet (33·40 g/kg of dietary protein).

The aim of the present study was to explore the influence of tea consumption on diabetes mellitus in the Chinese population. This multi-centre, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12 017 subjects aged 20–70 years. Socio-demographic and general information was collected by a standardised questionnaire. A standard procedure was used to measure anthropometric characteristics and to obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10 825 participants were included and multiple logistic models and interaction effect analysis were applied for assessing the association between tea drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted OR for newly diagnosed diabetes were 0·80 (95 % CI 0·67, 0·97), 0·88 (95 % CI 0·71, 1·09) and 0·86 (95 % CI 0·67, 1·11) for daily tea drinkers, occasional tea drinkers and seldom tea drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in females by 32 %, elderly (>45 years) by 24 % and obese (BMI > 30 kg/m2) by 34 %. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45 % (OR 0·55; 95 % CI 0·42, 0·72; P < 0·01). The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of type 2 diabetes mellitus.

Background: Endovascular thrombectomy (EVT) has shown efficacy in acute ischemic stroke (AIS) patients with infective endocarditis (IE). The possibility to undertake advanced histopathological clot analysis following EVT offers a new avenue to establish the etiological basis of the stroke – which is often labelled “cryptogenic.” In this paper, we present our findings from four consecutive patients with IE who underwent EVT following an AIS at our tertiary referral comprehensive stroke centre. Methods: Comprehensive histopathological analysis of clot retrieved after EVT, including morphology, was undertaken. Results: The consistent observation was the presence of dense paucicellular fibrinoid material mixed/interspersed with clusters of bacterial cocci. This clot morphology may be specific to septic embolus due to IE unlike incidental bacteraemia and could possibly explain the refractoriness of such clots to systemic thrombolysis. Conclusion: Detailed morphological and histopathological analysis of EVT-retrieved clots including Gram staining can assist in etiological classification of the clot. Understanding the composition of the clot may be of clinical value in early diagnostics and mapping treatment planning in IE.

This article examines Buddhist and Jaina attitudes towards the salvation of the Magadhan king Ajātaśatru (alias Kūṇika), a narrative character found in both Buddhist and Jaina traditions. A number of Buddhist texts prophesy that Ajātaśatru, despite his next birth in hell, will attain liberation in his final birth. Jaina sources also speak of Kūṇika's descent into hell, but give no prophecy of his ultimate liberation. While the Buddhists offered various solutions to Ajātaśatru's sinful condition, the Jainas proposed no remedy to mitigate the consequences of Kūṇika's sins. The Buddhist prophecies of Ajātaśatru's eventual liberation indicate that some Buddhists in ancient India were particularly concerned with the salvation of an archetypal villain such as Ajātaśatru. The Jaina silence on Kūṇika's destiny suggests that the Jainas in general had little interest in bringing this violent figure to liberation, and deemed him incapable of overcoming his “false view of reality” (mithyātva) due to his strong passions.

The dynamic response to shear of a fluid-filled square cavity with stable temperature stratification is investigated numerically. The shear is imposed by the constant translation of the top lid, and is quantified by the associated Reynolds number. The stratification, quantified by a Richardson number, is imposed by maintaining the temperature of the top lid at a higher constant temperature than that of the bottom, and the side walls are insulating. The Navier–Stokes equations under the Boussinesq approximation are solved, using a pseudospectral approximation, over a wide range of Reynolds and Richardson numbers. Particular attention is paid to the dynamical mechanisms associated with the onset of instability of steady state solutions, and to the complex and rich dynamics occurring beyond.

The flow response of a rapidly rotating fluid-filled cube to low-amplitude librational forcing is investigated numerically. Librational forcing is the harmonic modulation of the mean rotation rate. The rotating cube supports inertial waves which may be excited by libration frequencies less than twice the rotation frequency. The response is comprised of two main components: resonant excitation of the inviscid inertial eigenmodes of the cube, and internal shear layers whose orientation is governed by the inviscid dispersion relation. The internal shear layers are driven by the fluxes in the forced boundary layers on walls orthogonal to the rotation axis and originate at the edges where these walls meet the walls parallel to the rotation axis, and are hence called edge beams. The relative contributions to the response from these components is obscured if the mean rotation period is not small enough compared to the viscous dissipation time, i.e. if the Ekman number is too large. We conduct simulations of the Navier–Stokes equations with no-slip boundary conditions using parameter values corresponding to a recent set of laboratory experiments, and reproduce the experimental observations and measurements. Then, we reduce the Ekman number by one and a half orders of magnitude, allowing for a better identification and quantification of the contributions to the response from the eigenmodes and the edge beams.

Salt, promoting oxidative stress, contributes to insulin resistance, whereas K, inhibiting oxidative stress, improves insulin sensitivity. Oxidative stress activation of NLRP3 inflammasome is a central player in the induction of insulin resistance. Therefore, we hypothesised that NLRP3 inflammasome may mediate the effects of salt and K on insulin resistance. In all, fifty normotensive subjects were recruited from a rural community of Northern China. The protocol included a low-salt diet for 7 d, then a high-salt diet for 7 d and a high-salt diet with K supplementation for another 7 d. In addition, THP-1 cells were cultured in different levels of Na with and without K. The results showed that salt loading elevated fasting blood glucose, insulin and C-peptide levels, as well as insulin resistance, whereas K supplementation reversed them. Meanwhile, additional K reversed the active effects of high salt on NLRP3 inflammasome in both the subjects and THP-1 cells, and the change of insulin resistance index notably related with the alteration of plasma IL-1β, the index of NLRP3 inflammasome activation, during intervention in the subjects. Additional K ameliorated oxidative stress induced by high salt in both the subjects and cultured THP-1 cells, and the change of oxidative stress related with the alteration of plasma IL-1β during intervention in the subjects. In vitro, antioxidant N-acetyl-l-cysteine significantly prevented the active effects of high Na or oxidant Rosup on NLRP3 inflammasome, so did K. Our study indicates that oxidative stress modulation of NLRP3 inflammasome may be involved in the impacts of Na and K on insulin resistance.

In a previous paper, an inviscid vortex force map approach was developed for the normal force of a flat plate at arbitrarily high angle of attack and leading/trailing edge force-producing critical regions were identified. In this paper, this vortex force map approach is extended to viscous flows and general airfoils, for both lift and drag forces due to vortices. The vortex force factors for the vortex force map are obtained here by using Howe’s integral force formula. A decomposed form of the force formula, ensuring vortices far away from the body have negligible effect on the force, is also derived. Using Joukowsky and NACA0012 airfoils for illustration, it is found that the vortex force map for general airfoils is similar to that of a flat plate, meaning that force-producing critical regions similar to those of a flat plate also exist for more general airfoils and for viscous flow. The vortex force approach is validated against NACA0012 at several angles of attack and Reynolds numbers, by using computational fluid dynamics.

This study aimed to determine the effects of supplementing the diet of adult Nile tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth performance, body composition, fatty acid composition and gene expression. Genetically Improved Farmed Tilapia fish with an initial body weight of 83·1 (sd 2·9) g were divided into six groups. Each group was hand-fed a semi-purified diet containing 1·7 (control diet), 4·0, 6·5, 11·5, 21·3 or 41·0 g PC/kg diet for 68 d. Supplemental PC improved the feed efficiency rate, which was highest in the 11·5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary PC increased PC content in the liver and decreased crude fat content in the liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with increasing dietary PC. Cytoplasmic phospholipase A2 and secreted phospholipase A2 mRNA expression were up-regulated in the brain and heart in PC-supplemented fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral tissue but increased expression in muscle. Hormone-sensitive lipase and lipoprotein lipase expression increased in the liver with increasing dietary PC. Growth hormone mRNA expression was reduced in the brain and insulin-like growth factor-1 mRNA expression in liver reduced with PC above 6·5 g/kg. Our results demonstrate that dietary supplementation with PC improves feed efficiency and reduces liver fat in adult Nile tilapia, without increasing weight gain, representing a novel dietary approach to reduce feed requirements and improve the health of Nile tilapia.

Soft X-ray spectro-tomography provides three-dimensional (3D) chemical mapping based on natural X-ray absorption properties. Since radiation damage is intrinsic to X-ray absorption, it is important to find ways to maximize signal within a given dose. For tomography, using the smallest number of tilt series images that gives a faithful reconstruction is one such method. Compressed sensing (CS) methods have relatively recently been applied to tomographic reconstruction algorithms, providing faithful 3D reconstructions with a much smaller number of projection images than when conventional reconstruction methods are used. Here, CS is applied in the context of scanning transmission X-ray microscopy tomography. Reconstructions by weighted back-projection, the simultaneous iterative reconstruction technique, and CS are compared. The effects of varying tilt angle increment and angular range for the tomographic reconstructions are examined. Optimization of the regularization parameter in the CS reconstruction is explored and discussed. The comparisons show that CS can provide improved reconstruction fidelity relative to weighted back-projection and simultaneous iterative reconstruction techniques, with increasingly pronounced advantages as the angular sampling is reduced. In particular, missing wedge artifacts are significantly reduced and there is enhanced recovery of sharp edges. Examples of using CS for low-dose scanning transmission X-ray microscopy spectroscopic tomography are presented.