Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and ...differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, β-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.
Aprotic Li–O2 batteries are promising candidates for next‐generation energy storage technologies owing to their high theoretical energy densities. However, their practically achievable specific ...energy is largely limited by the need for porous conducting matrices as cathode support and the passivation of cathode surface by the insulating Li2O2 product. Herein, a self‐standing and hierarchically porous carbon framework is reported with Co nanoparticles embedded within developed by 3D‐printing of cobalt‐based metal–organic framework (Co‐MOF) using an extrusion‐based printer, followed by appropriate annealing. The novel self‐standing framework possesses good conductivity and necessary mechanical stability, so that it can act as a porous conducting matrix. Moreover, the porous framework consists of abundant micrometer‐sized pores formed between Co‐MOF‐derived carbon flakes and meso‐ and micropores formed within the flakes, which together significantly benefit the efficient deposition of Li2O2 particles and facilitate their decomposition due to the confinement of insulating Li2O2 within the pores and the presence of Co electrocatalysts. Therefore, the self‐standing porous architecture significantly enhances the cell's practical specific energy, achieving a high value of 798 Wh kg−1cell. This study provides an effective approach to increase the practical specific energy for Li–O2 batteries by constructing 3D‐printed framework cathodes.
3D‐printed cobalt (Co)‐based metal–organic framework–derived carbon framework with a hierarchically porous network and embedded with Co nanocatalysts is developed via a extrusion‐based method. The self‐standing framework acts as a porous conducting matrix for the cathode, and the desired micrometer‐sized pores formed between carbon flakes efficiently accumulate Li2O2 particles, which together significantly increases the practical specific energy of Li–O2 batteries.
Multifunctional structural batteries have gained interest in recent years due to their capability to simultaneously store electrochemical energy and bear mechanical load. The structural cathode is an ...integral component to form multifunctional structural batteries, and its electrochemical and mechanical performance are highly dependent on the fabrication process. Thus, this review aims to explore the fabrication techniques for these cathodes via indirect (casting, dip coating and layer-by-layer assembly, electrophoretic deposition, vacuum filtration & use of polymer matrix) and direct (synthesis) methods. Challenges and improvements in fabricating structural cathodes specific to these techniques will also be put forth, and the influence of cathode microstructure on the electrochemical and mechanical performances will also be discussed. This review also aims to introduce a performance metric using multifunctional efficiency as a basis for comparison when evaluating the multifunctional performance of structural cathodes. Future considerations on improving energy storage and load-bearing capability of structural cathodes will also be highlighted in order to develop more robust and efficient structural batteries.
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By providing objective measures, resilience metrics (RMs) help planners, designers, and decisionmakers to have a grasp of the resilience status of a system. Conceptual frameworks establish a sound ...basis for RM development. However, a significant challenge that has yet to be addressed is the assessment of the validity of RMs, whether they reflect all abilities of a resilient system, and whether or not they overrate/underrate these abilities. This article covers this gap by introducing a methodology that can show the validity of an RM against its conceptual framework. This methodology combines experimental design methods and statistical analysis techniques that provide an insight into the RM's quality. We also propose a new metric that can be used for general systems. The analysis of the proposed metric using the presented methodology shows that this metric is a better indicator of the system's abilities compared to the existing metrics.
Significant challenges currently prohibit expressive interaction in virtual reality (VR). Occlusions introduced by head-mounted displays (HMDs) make existing facial tracking techniques intractable, ...and even state-of-the-art techniques used for real-time facial tracking in unconstrained environments fail to capture subtle details of the user's facial expressions that are essential for compelling speech animation. We introduce a novel system for HMD users to control a digital avatar in real-time while producing plausible speech animation and emotional expressions. Using a monocular camera attached to an HMD, we record multiple subjects performing various facial expressions and speaking several phonetically-balanced sentences. These images are used with artist-generated animation data corresponding to these sequences to train a convolutional neural network (CNN) to regress images of a user's mouth region to the parameters that control a digital avatar. To make training this system more tractable, we use audio-based alignment techniques to map images of multiple users making the same utterance to the corresponding animation parameters. We demonstrate that this approach is also feasible for tracking the expressions around the user's eye region with an internal infrared (IR) camera, thereby enabling full facial tracking. This system requires no user-specific calibration, uses easily obtainable consumer hardware, and produces high-quality animations of speech and emotional expressions. Finally, we demonstrate the quality of our system on a variety of subjects and evaluate its performance against state-of-the-art real-time facial tracking techniques.
Despite intense interests in developing blood measurements of Alzheimer's disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we ...present a dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins - exosome-bound vs. unbound - directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.
To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children in Great Britain.
A nationally representative cross-sectional study survey of children (1102) aged 4-18 years ...(999 white, 570 male) living in private households (January 1997-1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L).
Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4-63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53-59 degrees latitude had lower levels (compared with 50-53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14-18 years old), odds ratio (OR) = 3.6 (95%CI 1.8-7.2) compared with younger children (4-8 years); non white children (OR = 37 95%CI 15-90); blood levels taken December-May (OR = 6.5 95%CI 4.3-10.1); on income support (OR = 2.2 95%CI 1.3-3.9); not taking vitamin D supplementation (OR = 3.7 95%CI 1.4-9.8); being overweight (OR 1.6 95%CI 1.0-2.5); <1/2 hour outdoor exercise/day/week (OR = 1.5 95%CI 1.0-2.3); watched >2.5 hours of TV/day/week (OR = 1.695%CI 1.0-2.4).
We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children.
Phagocytosis, a critical early event in the microbicidal response of neutrophils, is now appreciated to serve multiple functions in a variety of cell types. Professional phagocytes play a central ...role in innate immunity by eliminating pathogenic bacteria, fungi and malignant cells, and contribute to adaptive immunity by presenting antigens to lymphocytes. In addition, phagocytes play a part in tissue remodeling and maintain overall homeostasis by disposing of apoptotic cells, a task shared by non-professional phagocytes, often of epithelial origin. This functional versatility is supported by a vast array of receptors capable of recognizing a striking variety of foreign and endogenous ligands. Here we present an abbreviated overview of the different types of phagocytes, their varied modes of signaling and particle engulfment, and the multiple physiological roles of phagocytosis.
We demonstrate one-dimensional sub-Doppler laser cooling of a beam of YbF molecules to 100 μK. This is a key step towards a measurement of the electron's electric dipole moment using ultracold ...molecules. We compare the effectiveness of magnetically assisted and polarization-gradient sub-Doppler cooling mechanisms. We model the experiment and find good agreement with our data.
Few studies have examined the associations between sleep duration, shiftwork, and exercise to the infrequent menstruation, hyperandrogenism, and ovarian morphological changes observed in women with ...polycystic ovarian syndrome (PCOS).
To examine whether lifestyle factors, including short sleep duration, insufficient exercise, and shiftwork, alone or in combination, are associated with the reproductive and metabolic abnormalities typical of PCOS in a healthy population.
Prospective cross-sectional study of 231 women, including healthcare workers recruited for an annual health screen, healthy referral patients from the Women's Clinic and volunteers from the university community at the National University Hospital, Singapore, from 2011 to 2015.
The women completed a questionnaire, including their menstrual cycle length, sleep length, frequency of exercise and shift work. Hyperandrogenism (hirsutism score, testosterone, sex hormone binding globulin (SHBG)), ovarian morphology and function (anthral follicle count, ovarian volume, anti-mullerian hormone (AMH)), and metabolic measures (body mass index (BMI), waist hip ratio (WHR), blood pressure, fasting glucose, fasting insulin and fasting lipids) were examined through anthropometric measurements, transvaginal ultrasound scans, and blood tests.
No significant associations were observed between shift work, exercise or sleep duration and the androgenic and ovarian measures that define PCOS. However, women reporting fewer than 6 hours of sleep were more likely to report abnormal (short or long) menstrual cycle lengths (OR = 2.1; 95% CI, 1.1 to 4.2). Women who reported fewer than 6 hours of sleep had increased fasting insulin levels (difference in means = 2.13; 95% CI, 0.27 to 3.99 mU/L) and higher odds of insulin resistance (OR = 2.58; CI, 1.16 to 5.76). Lack of regular exercise was associated with higher mean fasting insulin (difference in means = 2.3 mU/L; 95% CI, 0.5 to 4.1) and HOMA-IR (difference in means = 0.49; 95% CI, 0.09 to 0.90) levels.
Women with insufficient sleep are at increased risk of menstrual disturbances and insulin resistance, but do not have the hyperandrogenism and polycystic ovarian morphology typical of PCOS.
Improved sleep duration may help reduce the risks of diabetes or infertility. Shift work, exercise or sleep duration appear not to impact the androgenic and ovarian measures that define PCOS.
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