Cyclin D3 deficiency inhibits skin tumor development, but does not affect normal keratinocyte proliferation.

Rearrangement and amplification of the D-type cyclin genes have been reported in human cancer. Previous studies have demonstrated that Ras-mediated skin tumorigenesis depends on pathways that act through cyclin D1 and D2; however, the role of cyclin D3 remains unknown. The present study demonstrates that cyclin D3 ablation does not affect keratinocyte proliferation, but instead increases apoptosis levels in the bulge region of the hair follicle. Consequently, cyclin D3 ablation reduces skin papilloma development in a Ras-dependent carcinogenesis model. Previous results revealed that cyclin D3 preferentially binds to cyclin-dependent kinase 6 (CDK6) in mouse keratinocytes and transgenic expression of CDK6 (K5CDK6 mice) inhibits skin tumor development. Thus, we hypothesized that the inhibitory effect of CDK6 is dependent on cyclin D3 expression. To test this hypothesis, a mouse model that overexpresses CDK6 and does not express cyclin D3 (K5CDK6/cyclin D3-/- compound mouse) was developed. Biochemical analysis of the epidermis of K5CDK6/cyclin D3-/- mice revealed that cyclin D3 ablation resulted in increased expression of cyclin D1 protein, with a consequent elevation in the level of CDK6/cyclin D1 and CDK4/cyclin D1 complexes. These findings were concurrent with the increase skin papilloma malignant progression observed in K5CDK6/cyclin D3-/- mice. In summary the absence of cyclin D3 led to fewer number of papillomas in cyclin D3-ablated mice than in the wild-type owing to increased apoptosis, suggesting that alterations in cell survival are a crucial mechanism for crippling cellular defense against neoplasia. The results of the current study also suggest that although cyclin D3 expression does not alter the tumor suppressive role of CDK6 in skin carcinogenesis, the compensatory increase in cyclin D1 can shift the balance towards malignant progression

A Study on the Body Insulators for the Bushing for HTS Devices at Cryogenic Temperature

AbstractA bushing for high temperature superconducting devices (HTS bushing) is important because of applying high voltage to the cable or the winding of the transformer. It is cooled with liquid nitrogen (LN2) and is insulated with various insulators. For the development of the HTS bushing, it is necessary to know the fundamental characteristics of various insulators at cryogenic temperature.The electrical characteristics of the breakdown were studied under AC and impulse voltages. Also, the mechanical characteristics such as tensile strength in air and LN2 were studied. It was confirmed that GFRP is excellent not only electrical characteristics but also mechanical characteristics in LN2

The effect of wavy leading edges on aerofoil-gust interaction noise

High-order accurate numerical simulations are performed to investigate the effects of wavy leading edges (WLEs) on aerofoil–gust interaction (AGI) noise. The present study is based on periodic velocity disturbances predominantly in streamwise and vertical directions that are mainly responsible for the surface pressure fluctuation of an aerofoil. In general, the present results show that WLEs lead to reduced AGI noise. It is found that the ratio of the wavy leading-edge peak-to-peak amplitude (LEA) to the longitudinal wavelength of the incident gust (?g) is the most important factor for the reduction of AGI noise. It is observed that there exists a tendency that the reduction of AGI noise increases with LEA/?g and the noise reduction is significant for LEA/?g?0.3. The present results also suggest that any two different cases with the same LEA/?g lead to a strong similarity in their profiles of noise reduction relative to the straight leading-edge case. The wavelength of wavy leading edges (LEW), however, shows minor influence on the reduction of AGI noise under the present gust profiles used. Nevertheless, the present results show that a meaningful improvement in noise reduction may be achieved when 1.0?LEW/?g?1.5. In addition, it is found that the beneficial effects of WLEs are maintained for various flow incidence angles and aerofoil thicknesses. Also, the WLEs remain effective for gust profiles containing multiple frequency components. It is discovered in this paper that WLEs result in incoherent response time to the incident gust across the span, which results in a decreased level of surface pressure fluctuations, hence a reduced level of AGI noise

Compact single-shot hyperspectral imaging using a prism

We present a novel, compact single-shot hyperspectral imaging method. It enables capturing hyperspectral images using a conventional DSLR camera equipped with just an ordinary refractive prism in front of the camera lens. Our computational imaging method reconstructs the full spectral information of a scene from dispersion over edges. Our setup requires no coded aperture mask, no slit, and no collimating optics, which are necessary for traditional hyperspectral imaging systems. It is thus very cost-effective, while still highly accurate. We tackle two main problems: First, since we do not rely on collimation, the sensor records a projection of the dispersion information, distorted by perspective. Second, available spectral cues are sparse, present only around object edges. We formulate an image formation model that can predict the perspective projection of dispersion, and a reconstruction method that can estimate the full spectral information of a scene from sparse dispersion information. Our results show that our method compares well with other state-of-the-art hyperspectral imaging systems, both in terms of spectral accuracy and spatial resolution, while being orders of magnitude cheaper than commercial imaging systems

Multi-object model-based multi-atlas segmentation for rodent brains using dense discrete correspondences

The delineation of rodent brain structures is challenging due to low-contrast multiple cortical and subcortical organs that are closely interfacing to each other. Atlas-based segmentation has been widely employed due to its ability to delineate multiple organs at the same time via image registration. The use of multiple atlases and subsequent label fusion techniques has further improved the robustness and accuracy of atlas-based segmentation. However, the accuracy of atlas-based segmentation is still prone to registration errors; for example, the segmentation of in vivo MR images can be less accurate and robust against image artifacts than the segmentation of post mortem images. In order to improve the accuracy and robustness of atlas-based segmentation, we propose a multi-object, model-based, multi-atlas segmentation method. We first establish spatial correspondences across atlases using a set of dense pseudo-landmark particles. We build a multi-object point distribution model using those particles in order to capture inter- and intra- subject variation among brain structures. The segmentation is obtained by fitting the model into a subject image, followed by label fusion process. Our result shows that the proposed method resulted in greater accuracy than comparable segmentation methods, including a widely used ANTs registration tool

Synergistic effect of a defect-free graphene nanostructure as an anode material for lithium ion batteries

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.Graphene nanosheets have been among the most promising candidates for a highperformance anode material to replace graphite in lithium ion batteries (LIBs). Studies in this area have mainly focused on nanostructured electrodes synthesized by graphene oxide (GO) or reduced graphene oxide (rGO) and surface modifications by a chemical treatment. Herein, we propose a cost-effective and reliable route for generating a defect-free, nanoporous graphene nanostructure (df-GNS) through the sequential insertion of pyridine into a potassium graphite intercalation compound (K-GIC). The as-prepared df-GNS preserves the intrinsic property of graphene without any crystal damage, leading to micro-/nano-porosity (microporosity: ~10–50 µm, nanoporosity: ~2– 20 nm) with a significantly large specific surface area. The electrochemical performance of the dfGNS as an anode electrode was assessed and showed a notably enhanced capacity, rate capability, and cycle stability, without fading in capacity or decaying. This is because of the optimal porosity, with perfect preservation of the graphene crystal, allowing faster ion access and a high amount of electron pathways onto the electrode. Therefore, our work will be very helpful for the development of anode and cathode electrodes with higher energy and power performance requirement

PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroblast activation.

The Notch/CSL pathway plays an important role in skin homeostasis and carcinogenesis. CSL, the key effector of canonical Notch signaling endowed with an intrinsic transcription repressive function, suppresses stromal fibroblast senescence and Cancer Associated Fibroblast (CAF) activation through direct down-modulation of key effector genes. Interacting proteins that participate with CSL in this context are as yet to be identified. We report here that Programmed Cell Death 4 (PDCD4), a nuclear/cytoplasmic shuttling protein with multiple functions, associates with CSL and plays a similar role in suppressing dermal fibroblast senescence and CAF activation. Like CSL, PDCD4 is down-regulated in stromal fibroblasts of premalignant skin actinic keratosis (AKs) lesions and squamous cell carcinoma (SCC). While devoid of intrinsic DNA binding capability, PDCD4 is present at CSL binding sites of CAF marker genes as well as canonical Notch/CSL targets and suppresses expression of these genes in a fibroblast-specific manner. Thus, we propose that PDCD4 is part of the CSL repressive complex involved in negative control of stromal fibroblasts conversion into CAFs

Enhanced cortical thickness measurements for rodent brains via Lagrangian-based RK4 streamline computation

The cortical thickness of the mammalian brain is an important morphological characteristic that can be used to investigate and observe the brain's developmental changes that might be caused by biologically toxic substances such as ethanol or cocaine. Although various cortical thickness analysis methods have been proposed that are applicable for human brain and have developed into well-validated open-source software packages, cortical thickness analysis methods for rodent brains have not yet become as robust and accurate as those designed for human brains. Based on a previously proposed cortical thickness measurement pipeline for rodent brain analysis,1 we present an enhanced cortical thickness pipeline in terms of accuracy and anatomical consistency. First, we propose a Lagrangian-based computational approach in the thickness measurement step in order to minimize local truncation error using the fourth-order Runge-Kutta method. Second, by constructing a line object for each streamline of the thickness measurement, we can visualize the way the thickness is measured and achieve sub-voxel accuracy by performing geometric post-processing. Last, with emphasis on the importance of an anatomically consistent partial differential equation (PDE) boundary map, we propose an automatic PDE boundary map generation algorithm that is specific to rodent brain anatomy, which does not require manual labeling. The results show that the proposed cortical thickness pipeline can produce statistically significant regions that are not observed in the previous cortical thickness analysis pipeline