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We numerically investigated the global linear instability and bifurcations in electro-thermo-convection (ETC) of a dielectric liquid confined in a two-dimensional (2-D) concentric annulus subjected to a strong unipolar injection. Seven kinds of solutions exist in this ETC system due to the complex bifurcations, i.e. saddle-node, subcritical and supercritical Hopf bifurcations. These bifurcation routes constitute at most four solution branches. Global linear instability analysis and energy analysis were conducted to explain the instability mechanism and transition of different solutions and to predict the local instability regions. The linearized lattice Boltzmann method (LLBM) for global linear instability analysis, first proposed by Pérez et al. (Theor. Comput. Fluid Dyn., vol. 31, 2017, pp. 643–664) to analyse incompressible flows, was extended here to solve the whole set of coupled linear equations, including the linear Navier–Stokes equations, the linear energy equation, Poisson's equation and the linear charge conservation equation. A multiscale analysis was also performed to recover the macroscopic linearized Navier–Stokes equations from the four different discrete lattice Boltzmann equations (LBEs). The LLBM was validated by calculating the linear critical value of 2-D natural convection; it has an error of 1.39% compared with the spectral method. Instability with global travelling wave behaviour is a unique behaviour in the annulus configuration electrothermohydrodynamic system, which may be caused by the baroclinity. Finally, the chaotic behaviour was quantitatively analysed through calculation of the fractal dimension and Lyapunov exponent.
Breast cancer is a high-risk disease with a high mortality rate among women. Chemotherapy plays an important role in the treatment of breast cancer. However, chemotherapy eventually results in tumours that are resistant to drugs. In recent years, many studies have revealed that the activation of Wnt/β-catenin signalling is crucial for the emergence and growth of breast tumours as well as the development of drug resistance. Additionally, drugs that target this pathway can reverse drug resistance in breast cancer therapy. Traditional Chinese medicine has the properties of multi-target and tenderness. Therefore, integrating traditional Chinese medicine and modern medicine into chemotherapy provides a new strategy for reversing the drug resistance of breast tumours. This paper mainly reviews the possible mechanism of Wnt/β-catenin in promoting the process of breast tumour drug resistance, and the progress of alkaloids extracted from traditional Chinese medicine in the targeting of this pathway in order to reverse the drug resistance of breast cancer.
OBJECTIVES/GOALS: Hamsters develop COVID-19 similarly to people because the SARS-CoV-2 spike protein binds with high affinity to hamster ACE2 resulting in host cell entry and replication. Our goal was to establish a hamster model that mirrors the lung and brain pathophysiology observed in COVID-19. METHODS/STUDY POPULATION: Hamsters infected with SARS CoV-2 are sacrificed on day 1 and day 6 postinfection. Lung histopathology scoring model was implemented for assessment all pathological relevant changes in the lungs of infected animals on tissue sections stained with hematoxylin and eosin. To quantify the extent and severity of lung pathology, two scoring systems were used: the first evaluated all relevant changes in the lungs of the infected animals and the second evaluated only the pathology associated with the pulmonary vasculature. Percentage of airway affected, airway severity, bronchiolar epithelial hyperplasia, alveoli affected, alveolar severity, type II pneumocyte hyperplasia and vessels affected were analyzed. Total airway score plus total lung alveolar score give lung histopathology score. RESULTS/ANTICIPATED RESULTS: Compared to the control hamster, the hamsters day 1 postinfection, exhibited a higher total airway score [9.00 ± 1.35 vs. 0.25 ± 0.1; p DISCUSSION/SIGNIFICANCE: Establishing this outstanding small animal model of COVID-19 will facilitate studies investigating diagnostics, prognosis and response to treatment in COVID-19 disease. These studies will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19.
OBJECTIVES/GOALS: Rodents are the most widely used experimental animals to study disease mechanisms due to their availability and cost-effectiveness. An international drive to investigate the pathophysiology of COVID-19 is inhibited by the resistance of rats and mice to SARS-CoV-2 infection. Our goal was to establish an appropriate small animal model. METHODS/STUDY POPULATION: To recreate the cytokine storm that is associated with COVID-19, we injected angiotensin converting enzyme 2 knockout (ACE2KO) mice (C57BI/6 strain) with lipopolysaccharide (LPS) intraperitoneally and measured the expression of multiple cytokines as a function of time and LPS dose. We then chose a minimum dose (500ug/kg) and time (3h) when multiple cytokines were elevated to measure lung injury scores using a point-counting technique on tissue sections stained with hematoxylin and eosin. The data are expressed as mean percentage of grid points lying within the peribronchial and superficial area in up to 20 fields. Percentage of peribronchial and superficial intrapulmonary hemorrhage, congestion, neutrophil infiltration and area of alveolar space were all assessed. RESULTS/ANTICIPATED RESULTS: Compared to the wildtype group (WT-G), the LPS-injected ACE2KO mice (LPS-G) exhibited a higher percentage of peribronchial intrapulmonary hemorrhage [(%): LPS-G, 10.56 ± 2.06 vs. WT-G, 5.59 ± 0.53; p DISCUSSION/SIGNIFICANCE: Establishing this novel mouse model of COVID-19 will facilitate studies investigating tissue-specific mechanisms of pathogenesis in this disease. This model can also be used to discover novel therapeutic targets and the design of clinical trials focusing on diagnostics, treatments and outcomes in COVID-19.
In this article, we show that firms can become conservative in innovation when their directors face job insecurity. We find that after the staggered enactment of majority voting legislation that strengthens shareholders’ power in director elections, firms produce fewer patents, particularly exploratory patents, and fewer forward citations. This effect is stronger for directors facing higher dismissal costs or threats and for firms with greater needs for board expertise and is mitigated by institutional investors’ expertise in innovation. Overall, our results suggest that heightened job insecurity induces director myopia, which leads to a reduction in investment in risky, long-term innovation projects.
This paper presents a feedforward compensation approach for musculoskeletal systems (MSs). Compared with traditional rigid robots, human arms have the advantages of flexibility and safety in operation in unstructured environments. However, the influence of external unknown disturbances, inner friction effects, and dynamic uncertainties of the MS makes it difficult to model and practically apply. In order to reduce the inner friction effects of the hardware platform and the over-relaxation/tension of the cable-pull drive, a feedforward friction compensation method for the cable-pulled artificial muscle unit is proposed. The method analyzes the friction causes of the hardware structure and establishes a mapping network relationship between the joint variables and the muscle force error in the muscle space. The experimental results show that the method can effectively improve the control accuracy and reduce the artificial muscle over-relaxation/tension instability.
We report that vertical vibration with small amplitude and high frequency can tame convective heat transport in Rayleigh–Bénard convection in a turbulent regime. When vertical vibration is applied, a dynamically averaged ‘anti-gravity’ results that stabilizes the thermal boundary layer and inhibits the eruption of thermal plumes. This eventually leads to the attenuation of the intensity of large-scale mean flow and a significant suppression of turbulent heat transport. Accounting for both the thermally led buoyancy and the vibration-induced anti-gravitational effects, we propose an effective Rayleigh number that helps to extend the Grossmann–Lohse theory to thermal vibrational turbulence. The prediction of the reduction on both the Nusselt and Reynolds numbers obtained by the extended model is found to agree well with the numerical data. In addition, vibrational influences on the mean flow structure and the temporal evolution of Nusselt and Reynolds numbers are investigated. The non-uniform characteristic of vibration-induced ‘anti-gravity’ is discussed. The present findings provide a powerful basis for studying thermal vibrational turbulence and put forward a novel strategy for actively controlling thermal turbulence.
Modal global linear stability analysis of thermal convection is performed with the linearized lattice Boltzmann method (LLBM). The onset of Rayleigh–Bénard convection in rectangular cavities with conducting and adiabatic sidewalls and the instability of two-dimensional (2-D) and three-dimensional (3-D) natural convection in cavities are studied. The method of linearizing the local equilibrium probability distribution function that was first proposed by Pérez et al. (Theor. Comp. Fluid Dyn., vol. 31, 2017, pp. 643–664) is extended to solve the coupled linear Navier–Stokes equations together with the linear energy equation in this work. A multiscale analysis is also performed to recover the macroscopic linear Navier–Stokes equations from the discrete lattice Boltzmann equations for both the single and multiple relaxation time models. The present LLBM is implemented in the framework of the Palabos library. It is validated by calculating the linear critical value of 2-D natural convection that the LLBM with the multiple relaxation time model has an error less than 1 % compared with the spectral method. The instability mechanism of the flow is explained by kinetic energy transfer analysis. It is shown that the buoyancy mechanism and inertial mechanism tend to stabilize the Hopf bifurcation of the 2-D natural convection at Pr < 0.08 and Pr > 1, respectively. For 3-D natural convection, subcritical bifurcation of the Hopf type is found for low-Prandtl-number fluids (Pr < 0.1).
When designing programs to assist the poor, it is important to recognize who is most in need of government assistance. Although measures of poverty are often based on income alone, poverty measures based on both income and assets provide greater precision in the analysis of this group since accumulated assets can be liquidated to compensate for temporary shortfalls in income. The current study used the Panel Study of Income Dynamics (2007–2017) to analyze associations between different facets of poverty dynamics (i.e. poverty entry and exit) and its determinants. We explored differences in results based on whether poverty was measured by income alone, or income plus assets. The Cox proportional hazard regression was used to examine how demographic characteristics predicted poverty entry and poverty exit. Results indicated factors predicting poverty entry were not identical to those predicting difficulty of exiting poverty. Also, the risk of poverty entry and exit differed based on whether poverty was measured by income alone, or income plus assets. Thus, using income plus assets provides new perspectives into poverty dynamics which past research, based on income alone, did not provide. These new insights can be used to inform decisions about policies for poverty prevention and alleviation.
Emotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.
In total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.
Compared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.
The cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.
Host density is a key regulatory factor in parasite transmission. The goldfish (Carassius auratus)-Gyrodactylus kobayashii model was used to investigate effects of host density on population growth of gyrodactylids. A donor fish infected by five gravid gyrodactylids was mixed with 11 parasite-free goldfish at five host densities. There was a significant positive correlation between host density and mean abundance of G. kobayashii throughout the 58-day experiment. During early infection (days 15–24), mean abundance in medium high (0.5 fish L−1) and high host density groups (1 and 2 fish L−1) was significantly higher than that in the low host density groups (0.125 and 0.25 fish L−1). At high host density, prevalence increased more rapidly, and the peak prevalence was higher. Fitting of an exponential growth model showed that the population growth rate of the parasite increased with host density. A hypothesis was proposed that higher host density contributed to increased reinfection of detached gyrodactylids. A reinfection experiment was designed to test this hypothesis. Both mean abundance and prevalence at a host density of 1 fish L−1 were significantly higher than those at 0.25 fish L−1 on days 1 and 3, which suggested that more reinfections of G. kobyashii occurred at the higher host density. Density-dependent transmission during the early infection was an important contributor of population growth of G. kobayashii, as well as density-dependent reinfection of the detached gyrodactylids.
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 purpose of the current study was to develop a validated FFQ to evaluate the intake of non-nutritive sweeteners (NNS) in child and adolescent Asian populations.
Intensive and overall market research was performed to create the applicable NNS-FFQ with thirteen food categories and 305 items. Six intense sweeteners, including acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides and sorbitol, were investigated. The validity and reproducibility of the NNS-FFQ were evaluated. The validity was further assessed by examining the consistency of reported NNS intake compared with urinary biomarkers using Cohen’s κ analysis.
This work was considered to be relevant in Asian societies.
One hundred and two children and adolescents recruited from several clinics were invited to participate in the current study.
High content validity indices and high content validity ratio levels were revealed for each sweetener and food category. Reproducibility among subjects was satisfactory. Significant moderate correlations between estimated steviol glycoside/sucralose consumption and sensitive urinary biomarker levels were demonstrated (κ values were 0·59 and 0·45 for steviol glycosides and sucralose, respectively), indicating that the NNS-FFQ can be used to assess an individual’s NNS intake. The dietary intense sweetener consumption pattern evaluated in this measurement was similar to those observed in other Asian countries but differed from those observed in Western populations with respect to types and amounts of NNS.
This validated NNS-FFQ can be an applicable and useful tool to evaluate NNS intake in future epidemiological and clinical studies.
Using a new trademark-based product market competition measure and a novel trademark-merger data set over the period 1983–2016, we show that companies facing greater product market competition are more likely to be acquirers. We further show that postmerger, compared to their nonacquiring peers, acquirers consolidate their product offerings by discontinuing more existing product lines and developing fewer new product lines. Using a quasi-experiment based on bids withdrawn due to exogenous reasons helps us establish the causal effect of deal completion on product-market consolidation. We conclude that acquisitions create product market synergies by cutting overlapping product offerings to achieve cost efficiency.
Neuroimaging- and machine-learning-based brain-age prediction of schizophrenia is well established. However, the diagnostic significance and the effect of early medication on first-episode schizophrenia remains unclear.
To explore whether predicted brain age can be used as a biomarker for schizophrenia diagnosis, and the relationship between clinical characteristics and brain-predicted age difference (PAD), and the effects of early medication on predicted brain age.
The predicted model was built on 523 diffusion tensor imaging magnetic resonance imaging scans from healthy controls. First, the brain-PAD of 60 patients with first-episode schizophrenia, 60 healthy controls and 21 follow-up patients from the principal data-set and 40 pairs of individuals in the replication data-set were calculated. Next, the brain-PAD between groups were compared and the correlations between brain-PAD and clinical measurements were analysed.
The patients showed a significant increase in brain-PAD compared with healthy controls. After early medication, the brain-PAD of patients decreased significantly compared with baseline (P < 0.001). The fractional anisotropy value of 31/33 white matter tract features, which related to the brain-PAD scores, had significantly statistical differences before and after measurements (P < 0.05, false discovery rate corrected). Correlation analysis showed that the age gap was negatively associated with the positive score on the Positive and Negative Syndrome Scale in the principal data-set (r = −0.326, P = 0.014).
The brain age of patients with first-episode schizophrenia may be older than their chronological age. Early medication holds promise for improving the patient's brain ageing. Neuroimaging-based brain-age prediction can provide novel insights into the understanding of schizophrenia.
The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1–2 years), preschool (3–5 years), primary or elementary school (6–11 years), and adolescence (10–18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0–18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia).
PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex.
Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3–406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5–417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4–1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60–2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7–50.4)].
The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.
Echinococcus shiquicus is currently limited to the Qinghai–Tibet plateau, a large mountainous region in China. Although the zoonotic potential remains unknown, progress is being made on the distribution and intermediate host range. In this study, we report E. shiquicus within Gansu and Qinghai provinces in regions located not only around the central areas but also the southeast edge of the plateau and describe their genetic relationship with previous isolates from the plateau. From 1879 plateau pikas examined, 2.39% (95% CI 1.79–3.18) were infected with E. shiquicus. The highest prevalence of 10.26% (4.06–23.58) was recorded in Makehe town, Qinghai province. Overall the prevalence was marginally higher in Qinghai (2.5%, CI 1.82–3.43) than in Gansu (2%, CI 1.02–3.89). The cox1 and nad1 genes demonstrated high and low haplotype and nucleotide diversities, respectively. The median-joining network constructed by the cox1–nad1 gene sequences demonstrated a star-like configuration with a median vector (unsampled haplotype) occupying the centre of the network. No peculiar distinction or common haplotype was observed in isolates originating from the different provinces. The presence of E. shiquicus in regions of the southeast and northeast edges of the Qinghai–Tibet plateau and high genetic variation warrants more investigation into the haplotype distribution and genetic polymorphism by exploring more informative DNA regions of the mitochondrial genome to provide epidemiologically useful insight into the population structure of E. shiquicus across the plateau and its axis.
This study aimed to evaluate to what extent the different interval times between trophectoderm (TE) biopsy and vitrification influence the clinical outcomes in preimplantation genetic testing (PGT) cycles. Patients who underwent frozen embryo transfer (FET) after PGT between 2015 and 2019 were recruited. In total, 297 cycles with single day 5 euploid blastocyst transfer were included. These cycles were divided into three groups according to the interval times: <1 h group, 1–2 h group, and ≥2 h group. Blastocyst survival, clinical pregnancy, miscarriage, and ongoing pregnancy rates were compared. The results showed that, in PGT-SR cycles, survival rate in the ≥2 h group (96.72%) was significantly lower than in the <1 h group (100%, P = 0.047). The clinical pregnancy rate in the ≥2 h group was 55.93%, significantly lower than in the <1 h group (74.26%, P = 0.017). The ongoing pregnancy rates in the 1–2 h group and the ≥2 h group were 48.28% and 47.46%, respectively, significantly lower than that in the <1 h group (67.33%, P < 0.05). The miscarriage rate in the 1–2 h group was 18.42%, significantly higher than that in the <1 h group (5.33%, P = 0.027). In PGT-A cycles, the clinical pregnancy and ongoing pregnancy rates in the <1 h group were 67.44% and 53.49%, respectively, higher than that in the 1–2 h group (52.94%, 47.06%, P > 0.05) and the ≥2 h group (52.63%, 36.84%, P > 0.05). In conclusion, vitrification of blastocysts beyond 1 h after biopsy significantly influences embryo survival and clinical outcomes and is therefore not recommended.