Detection of REM Sleep Behaviour Disorder by Automated Polysomnography Analysis

Evidence suggests Rapid-Eye-Movement (REM) Sleep Behaviour Disorder (RBD) is an early predictor of Parkinson's disease. This study proposes a fully-automated framework for RBD detection consisting of automated sleep staging followed by RBD identification. Analysis was assessed using a limited polysomnography montage from 53 participants with RBD and 53 age-matched healthy controls. Sleep stage classification was achieved using a Random Forest (RF) classifier and 156 features extracted from electroencephalogram (EEG), electrooculogram (EOG) and electromyogram (EMG) channels. For RBD detection, a RF classifier was trained combining established techniques to quantify muscle atonia with additional features that incorporate sleep architecture and the EMG fractal exponent. Automated multi-state sleep staging achieved a 0.62 Cohen's Kappa score. RBD detection accuracy improved by 10% to 96% (compared to individual established metrics) when using manually annotated sleep staging. Accuracy remained high (92%) when using automated sleep staging. This study outperforms established metrics and demonstrates that incorporating sleep architecture and sleep stage transitions can benefit RBD detection. This study also achieved automated sleep staging with a level of accuracy comparable to manual annotation. This study validates a tractable, fully-automated, and sensitive pipeline for RBD identification that could be translated to wearable take-home technology.Comment: 20 pages, 3 figure

Detection of Functional Matrix Metalloproteinases by Zymography

Matrix metalloproteinases (MMPs) are zinc-containing endopeptidases. They degrade proteins by cleavage of peptide bonds. More than twenty MMPs have been identified and are separated into six groups based on their structure and substrate specificity (collagenases, gelatinases, membrane type [MT-MMP], stromelysins, matrilysins, and others). MMPs play a critical role in cell invasion, cartilage degradation, tissue remodeling, wound healing, and embryogenesis. They therefore participate in both normal processes and in the pathogenesis of many diseases, such as rheumatoid arthritis, cancer, or chronic obstructive pulmonary disease1-6. Here, we will focus on MMP-2 (gelatinase A, type IV collagenase), a widely expressed MMP. We will demonstrate how to detect MMP-2 in cell culture supernatants by zymography, a commonly used, simple, and yet very sensitive technique first described in 1980 by C. Heussen and E.B. Dowdle7-10. This technique is semi-quantitative, it can therefore be used to determine MMP levels in test samples when known concentrations of recombinant MMP are loaded on the same gel11

Genetic Algorithm-Based Approaches for Solving Inexact Optimization Problems and their Applications for Municipal Solid Waste Management

This chapter proposes a genetic algorithm (GA)-based approach as an all-purpose problem-solving method for optimization problems with uncertainty. This chapter explains the GA-based method and presents details on the computation procedures involved for solving the three types of inexact optimization problems, which include the ILP, inexact quadratic programming (IQP) and inexact nonlinear programming (INLP) optimization problems

Induction of WNT16 via peptide-mRNA nanoparticle-based delivery maintains cartilage homeostasis

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants antagonizes canonical β-catenin/WNT3a signaling, leading to increased lubricin production and decreased chondrocyte apoptosis. This is a proof-of-concept study showing that mRNA can be efficiently delivered to articular cartilage, an avascular tissue that is poorly accessible even when drugs are intra-articularly (IA) administered. The ability to accommodate a wide range of oligonucleotides suggests that this platform may find use in a broad range of clinical applications

Charged particle detection performances of CMOS pixel sensors produced in a 0.18 um process with a high resistivity epitaxial layer

The apparatus of the ALICE experiment at CERN will be upgraded in 2017/18 during the second long shutdown of the LHC (LS2). A major motivation for this upgrade is to extend the physics reach for charmed and beauty particles down to low transverse momenta. This requires a substantial improvement of the spatial resolution and the data rate capability of the ALICE Inner Tracking System (ITS). To achieve this goal, the new ITS will be equipped with 50 um thin CMOS Pixel Sensors (CPS) covering either the 3 innermost layers or all the 7 layers of the detector. The CPS being developed for the ITS upgrade at IPHC (Strasbourg) is derived from the MIMOSA 28 sensor realised for the STAR-PXL at RHIC in a 0.35 um CMOS process. In order to satisfy the ITS upgrade requirements in terms of readout speed and radiation tolerance, a CMOS process with a reduced feature size and a high resistivity epitaxial layer should be exploited. In this respect, the charged particle detection performance and radiation hardness of the TowerJazz 0.18 um CMOS process were studied with the help of the first prototype chip MIMOSA 32. The beam tests performed with negative pions of 120 GeV/c at the CERN-SPS allowed to measure a signal-to-noise ratio (SNR) for the non-irradiated chip in the range between 22 and 32 depending on the pixel design. The chip irradiated with the combined dose of 1 MRad and 10^13 n_eq/cm^2 was observed to yield a SNR ranging between 11 and 23 for coolant temperatures varying from 15 C to 30 C. These SNR values were measured to result in particle detection efficiencies above 99.5% and 98% before and after irradiation respectively. These satisfactory results allow to validate the TowerJazz 0.18 um CMOS process for the ALICE ITS upgrade.Comment: (v2) Added hyper-links; (v3) A typo correcte

Age-related changes to macrophages are detrimental to fracture healing in mice.

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age-related diseases. Therefore, we investigated age-related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA-seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up-regulation of M1/pro-inflammatory genes in macrophages from old mice as well as dysregulation of other immune-related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age-matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA-seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age-related changes, and depleting infiltrating macrophages can improve fracture healing in old mice

Development of CMOS Pixel Sensors fully adapted to the ILD Vertex Detector Requirements

CMOS Pixel Sensors are making steady progress towards the specifications of the ILD vertex detector. Recent developments are summarised, which show that these devices are close to comply with all major requirements, in particular the read-out speed needed to cope with the beam related background. This achievement is grounded on the double- sided ladder concept, which allows combining signals generated by a single particle in two different sensors, one devoted to spatial resolution and the other to time stamp, both assembled on the same mechanical support. The status of the development is overviewed as well as the plans to finalise it using an advanced CMOS process.Comment: 2011 International Workshop on Future Linear Colliders (LCWS11), Granada, Spain, 26-30 September 201