Identification of Novel Therapeutic Targets for Polyglutamine Diseases That Target Mitochondrial Fragmentation

Huntington’s disease (HD) is one of at least nine polyglutamine diseases caused by a trinucleotide CAG repeat expansion, all of which lead to age-onset neurodegeneration. Mitochondrial dynamics and function are disrupted in HD and other polyglutamine diseases. While multiple studies have found beneficial effects from decreasing mitochondrial fragmentation in HD models by disrupting the mitochondrial fission protein DRP1, disrupting DRP1 can also have detrimental consequences in wild-type animals and HD models. In this work, we examine the effect of decreasing mitochondrial fragmentation in a neuronal C. elegans model of polyglutamine toxicity called Neur-67Q. We find that Neur-67Q worms exhibit mitochondrial fragmentation in GABAergic neurons and decreased mitochondrial function. Disruption of drp-1 eliminates differences in mitochondrial morphology and rescues deficits in both movement and longevity in Neur-67Q worms. In testing twenty-four RNA interference (RNAi) clones that decrease mitochondrial fragmentation, we identified eleven clones—each targeting a different gene—that increase movement and extend lifespan in Neur-67Q worms. Overall, we show that decreasing mitochondrial fragmentation may be an effective approach to treating polyglutamine diseases and we identify multiple novel genetic targets that circumvent the potential negative side effects of disrupting the primary mitochondrial fission gene drp-1.     

Starch Damage Part 1: Characterisation of Granule Damage in Ball-milled Potato Starch Study by SEM

Scanning electron microscopy (SEM) has been used to classify and quantify the types of damage evident in a population potato starch granules following ball milling. Whilst the majority of granules remained undamaged, a significant (p<0.01) increase in the number of granules with localized damage was observed (1.6% to 15.1%). A variety fo types of localised damage were discernable, ranging from areas where small amounts of granule surface material had been removed, to large areas possessing coarse surfaces caused by extensive removal of material. The generation of this latter category termed ‘rough faces’, was the most significant and predominant change following ball milling (p <0.05). Ball-milling was therefore attributed to the penetration of an outer granule layer, via the removal of surface material at existing points of weakness. This produced rough, disrupted areas of the granule surface, which are more likely to be susceptible to hydration and enzyme attack.     

以太网七要素

在工厂生产层使用以太网之前,必须了解它的七个要素。这里,我们以Profinet标准为例,为大家一一进行介绍。1.网络布局办公室的网络拓扑布局并不适用于工厂生产层,那里采用的是工厂/机器的以太网拓扑布局。办公室以太网的基础架构通常是由商业级的产品构建,它们在恒温的环境和星型拓扑构建的交换网络中可以很好地发挥作用;而与此不同,工业以太网架构常常要面对多变的意     

Post-test evaluation of oxygen electrodes from solid oxide electrolysis stacks

The oxygen electrodes from two solid oxide electrolysis stacks that performed high-temperature steam electrolysis (HTSE) and produced hydrogen for 1000 and 2000 h, respectively, were examined using X-ray fluorescence, X-ray absorption near edge structure (XANES), four-point resistivity, scanning electron microscopy, energy dispersive spectroscopy, X-ray diffraction and Raman micro-spectroscopy to determine possible causes for the degradation in stack performance over the test periods. These techniques yielded information such as elemental distribution, oxidation state, phases present, electrode delamination, and porosity within the electrode layers. From these studies, we found two phenomena that were likely the cause of increasingly poor oxygen electrode performance over time. The first source of degradation was chromium substitution into the oxygen electrode bond layer, which serves to bond the cell to the flow field and interconnect. This is caused by migration of a chromium species from the bipolar plate. The effect of this is a significant increase in the electrical resistance of the bond layer material. The other source of degradation identified was oxygen electrode delamination. The cause of electrode delamination, which is locally catastrophic to the operation of the cell, is unclear; however, we will discuss two possible mechanisms that might cause this phenomenon.     

Implementation,calibration and accuracy testing of an image-enhanced endoscopy system

This paper presents a new method for image-guided surgery called image-enhanced endoscopy. Registered real and virtual endoscopic images (perspective volume renderings generated from the same view as the endoscope camera using a preoperative image) are displayed simultaneously; when combined with the ability to vary tissue transparency in the virtual images, this provides surgeons with the ability to see beyond visible surfaces and, thus, provides additional exposure during surgery. A mount with four photoreflective spheres is rigidly attached to the endoscope and its position and orientation is tracked using an optical position sensor. Generation of virtual images that are accurately registered to the real endoscopic images requires calibration of the tracked endoscope. The calibration process determines intrinsic parameters (that represent the projection of three-dimensional points onto the two-dimensional endoscope camera imaging plane) and extrinsic parameters (that represent the transformation from the coordinate system of the tracker mount attached to the endoscope to the coordinate system of the endoscope camera), and determines radial lens distortion. The calibration routine is fast, automatic, accurate and reliable, and is insensitive to rotational orientation of the endoscope. The routine automatically detects, localizes, and identifies dots in a video image snapshot of the calibration target grid and determines the calibration parameters from the sets of known physical coordinates and localized image coordinates of the target grid dots. Using nonlinear lens-distortion correction, which can be performed at real-time rates (30 frames per second), the mean projection error is less than 0.5 mm at distances up to 25 mm from the endoscope tip, and less than 1.0 mm up to 45 mm. Experimental measurements and point-based registration error theory show that the tracking error is about 0.5-0.7 mm at the tip of the endoscope and less than 0.9 mm for all points in the field of view of the endoscope camera at a distance of up to 65 mm from the tip. It is probable that much of the projection error is due to endoscope tracking error rather than calibration error. Two examples of clinical applications are presented to illustrate the usefulness of image-enhanced endoscopy. This method is a useful addition to conventional image-guidance systems, which generally show only the position of the tip (and sometimes the orientation) of a surgical instrument or probe on reformatted image slices.     

Targeting HGF/c-MET Axis in Pancreatic Cancer

Pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC/PC)) has been an aggressive disease that is associated with early metastases. It is characterized by dense and collagenous desmoplasia/stroma, predominantly produced by pancreatic stellate cells (PSCs). PSCs interact with cancer cells as well as other stromal cells, facilitating disease progression. A candidate growth factor pathway that may mediate this interaction is the hepatocyte growth factor (HGF)/c-MET pathway. HGF is produced by PSCs and its receptor c-MET is expressed on pancreatic cancer cells and endothelial cells. The current review discusses the role of the MET/HGF axis in tumour progression and dissemination of pancreatic cancer. Therapeutic approaches that were developed targeting either the ligand (HGF) or the receptor (c-MET) have not been shown to translate well into clinical settings. We discuss a two-pronged approach of targeting both the components of this pathway to interrupt the stromal–tumour interactions, which may represent a potential therapeutic strategy to improve outcomes in PC.     

Additive manufacturing of zirconia parts with organic sacrificial supports

Ceramic On-Demand Extrusion (CODE) process has been recently proposed for additive manufacturing of strong ceramic components via extrusion. This paper focuses on fabricating 3 mol% yttria-stabilized zirconia (3YSZ) components using CODE process, and enabling CODE to produce parts with support structures. A colloidal suspension of 3YSZ was developed and deposited through the main nozzle, and an organic feedstock was developed and deposited by means of another nozzle to fabricate supports. After printing and drying of raw parts, supports were removed by increasing the temperature and parts were then sintered to near theoretical (~99%) density. The maximum overhang angle that could be built with no support was also found out to be approximately 60 degrees. Three organic support materials, that is, polycaprolactone (PCL), silicone, and petrolatum were prepared and tested. PCL and petrolatum were identified as feasible support materials. Specimens were fabricated to validate the efficiency of the support materials and to evaluate CODE's capability for building parts with complex geometry. The microstructures of these parts were also analyzed via scanning electron microscopy.     

A fast digital chip implementing a real-time noise-resistant algorithm for estimating blood pressure using a non-invasive,cuffless PPG sensor

Microsystem Technologies - A fast digital chip is designed and fabricated successfully to implement the algorithm for estimating blood pressure (BP) in real time by a non-invasive cuffless...