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Enhanced Objective Detection of Retinal Nerve Fiber Bundle Defects in Glaucoma With a Novel Method for En Face OCT Slab Image Construction and Analysis
Get PDFYesTo introduce and evaluate the performance in detecting glaucomatous abnormalities of a novel method for extracting en face slab images (SMAS), which considers varying individual anatomy and configuration of retinal nerve fiber bundles.
Dense central retinal spectral domain optical coherence tomography scans were acquired in 16 participants with glaucoma and 19 age-similar controls. Slab images were generated by averaging reflectivity over different depths below the inner limiting membrane according to several methods. SMAS considered multiple 16 µm thick slabs from 8 to 116 µm below the inner limiting membrane, whereas 5 alternative methods considered single summary slabs of various thicknesses and depths. Superpixels in eyes with glaucoma were considered abnormal if below the first percentile of distributions fitted to control data for each method. The ability to detect glaucoma defects was measured by the proportion of abnormal superpixels. Proportion of superpixels below the fitted first percentile in controls was used as a surrogate false-positive rate. The effects of slab methods on performance measures were evaluated with linear mixed models.
The ability to detect glaucoma defects varied between slab methods, χ2(5) = 120.9,
Two-Stage Stochastic Model to Invest in Distributed Generation Considering the Long-Term Uncertainties
Get PDFYesThis paper used different risk management indicators applied to the investment optimization performed by consumers in Distributed Generation (DG). The objective function is the total cost incurred by the consumer including the energy and capacity payments, the savings, and the revenues from the installation of DG, alongside the operation and maintenance (O&M) and investment costs. Probability density function (PDF) was used to model the price volatility in the long-term. The mathematical model uses a two-stage stochastic approach: investment and operational stages. The investment decisions are included in the first stage and which do not change with the scenarios of the uncertainty. The operation variables are in the second stage and, therefore, take different values with every realization. Three risk indicators were used to assess the uncertainty risk: Value-at-Risk (VaR), Conditional Value-at-Risk (CVaR), and Expected Value (EV). The results showed the importance of migration from deterministic models to stochastic ones and, most importantly, the understanding of the ramifications of every risk indicator
MIMO Antenna System for Modern 5G Handheld Devices with Healthcare and High Rate Delivery
Get PDFYesIn this work, a new prototype of the eight-element MIMO antenna system for 5G communications, internet of things, and networks has been proposed. This system is based on an H-shaped monopole antenna system that offers 200 MHz bandwidth ranges between 3.4-3.6GHz, and the isolation between any two elements is well below -12dB without using any decoupling structure. The proposed system is designed on a commercially available 0.8mm-thick FR4 substrate. One side of the chassis is used to place the radiating elements, while the copper from the other side is being removed to avoid short-circuiting with other components and devices. This also enables space for other systems, sub-systems, and components. A prototype is fabricated and excellent agreement is observed between the experimental and the computed results. It was found that ECC is 0.2 for any two radiating elements which is consistent with the desirable standards, and channel capacity is 38 bps/Hz which is 2.9 times higher than 4x4 MIMO configuration. In addition, single hand mode and dual hand mode analysis are conducted to understand the operation of the system under such operations and to identify losses and/or changes in the key performance parameters. Based on the results, the proposed antenna system will find its applications in modern 5G handheld devices and internet of things with healthcare and high rate delivery. Besides that, its design simplicity will make it applicable for mass production to be used in industrial demands
Green and Highly Efficient MIMO Transceiver System for 5G Heterogenous Networks
Get PDFYesThe paper presents the general requirements and an exemplary design of the RF front-end system that in today's handset is a key consumer of power. The design is required to minimize the carbon footprint in mobile handsets devices, whilst facilitating cooperation, and providing the energy-efficient operation of multi-standards for 5G communications. It provides the basis of hardware solutions for RF front-end integration challenges and offers design features covering energy efficiency for power amplifiers (PAs), Internet of Things (IoT) controlled tunable filters and compact highly isolated multiple-input and multiple-output (MIMO) antennas. An optimum design requires synergetic collaboration between academic institutions and industry in order to satisfy the key requirements of sub-6 GHz energy-efficient 5G transceivers, incorporating energy efficiency, good linearity and the potential for low-cost manufacturing. A highly integrated RF transceiver was designed and implemented to transmit and receive a picture using compact MIMO antennas integrated with efficient tunable filters and high linearity PAs. The proposed system has achieved a bit error rate (BER) of less than 10-10 at a data rate of 600 Mb/s with a wireless communication distance of more than 1 meter and power dissipation of 18-20 mW using hybrid beamforming technology and 64-QAM modulation.10.13039/100010665-H2020 Marie Skodowska Curi
Process Parameter Optimization of a Polymer Derived CeramicCoatings for Producing Ultra-High Gas Barrier
Get PDFYesSilica is one of the most efficient gas barrier materials, and hence is widely used as anencapsulating material for electronic devices. In general, the processing of silica is carried out at hightemperatures, i.e., around 1000◦C. Recently, processing of silica has been carried out from a polymercalled Perhydropolysilazane (PHPS). The PHPS reacts with environmental moisture or oxygen andyields pure silica. This material has attracted many researchers and has been widely used in manyapplications such as encapsulation of organic light-emitting diodes (OLED) displays, semiconductorindustries, and organic solar cells. In this paper, we have demonstrated the process optimization ofthe conversion of the PHPS into silica in terms of curing methods as well as curing the environment.Various curing methods including exposure to dry heat, damp heat, deep UV, and their combinationunder different environments were used to cure PHPS. FTIR analysis suggested that the quickestconversion method is the irradiation of PHPS with deep UV and simultaneous heating at 100◦C.Curing with this method yields a water permeation rate of 10−3g/(m2·day) and oxygen permeationrate of less than 10−1cm3/(m2·day·bar). Rapid curing at low-temperature processing along withbarrier properties makes PHPS an ideal encapsulating material for organic solar cell devices and avariety of similar applications.King Saud Universit
Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7
Get PDFChemokines are chemotactic cytokines, which mediate cell trafficking and play a key
role in mobilisation of leukocytes. More recently, chemokines and their cognate
receptors have been described as key players in different aspects of cancer biology
contributing to proliferation, angiogenesis and metastasis. In particular, chemokines
CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key
drivers of lymph node metastasis in a number of malignancies including breast, colon,
gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine
bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders
both peptides incapable of fully activating CCR7. However, little is known about the
nature of the interactions that occur between the N-terminal residues of CCL19 or
CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim
of this study is to investigate the role of the residues in the N-terminus of CCL19 and
in particular CCL21 in the context of CCR7 activation and to use this information in the
discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a
number of short (three to seven amino acids) peptides and peptidomimetics inspired
by the seven N-terminal amino acid residues of CCL19 and CCL21 and
pharmacologically characterised their ability to activate CCR7 or block the activation
of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden
chamber), and Western blotting. We also carried out computational studies to better
understand and predict the activity of these peptides. Our results demonstrate that
some of these peptides are indeed capable of acting as agonists or antagonists of
CCR7.Kuwait Health Ministry and Kuwait Civil Services Commissio
Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer
Get PDFYesEpidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. However, CYP2W1 was expressed in FaDu and Detroit-562 xenografts and in a cohort of human HNC samples. Functional activity was measured in Fadu and Detroit-562 cells using P450-Glo™ assay. Antiproliferative results of duocarmycin prodrugs ICT2700 and ICT2706 revealed FaDu and Detroit-562 as the most sensitive HNC cell lines. Administration of ICT2700 in vivo using a single dose of ICT2700 (150 mg/kg) showed preferential inhibition of small tumour growth (mean size of 60 mm3) in mice bearing FaDu xenografts. Significantly, our findings suggest a potential targeted therapeutic approach to manage HNCs by exploiting intratumoural CYP expression for metabolic activation of duocarmycin-based prodrugs such as ICT2700.The authors would like to thank Bradford Institute for Health Research for funding a PhD studentship to DP through a competitive scheme and Yorkshire Cancer Research programme Grant (B381PA) for supporting our cytochrome P450-focused drug discovery research
Peacebuilding Evaluations within International Organisations. Investigation of their relevance, roles and effects
Get PDFResponding to and preventing violent conflict continue to be a major concern on the international agenda. However, the results of peacebuilding projects are often mixed and some interventions have even proven harmful in the past. In the debates on aid effectiveness, evaluations have been advocated as being an effective instrument to better understand the results of development and peacebuilding projects and thereby ultimately to improve the practice. However, despite a long tradition of evaluation utilisation research dating back to the 1970s, the effects of peacebuilding evaluations are far from being understood. The concept of evaluation use is too narrow and does not take the diversity of potential positive and negative evaluation effects into account. There is little evidence concerning the organisational factors that influence the use and effects of evaluations. Using a comparative case study analysis in three organisations implementing peacebuilding activities (Deutsche Gesellschaft für Internationale Zusammenarbeit, Saferworld and the World Bank), this study examines the roles and effects of peacebuilding evaluations within international organisations. The results show a wide range of positive and negative evaluation effects that are promoted or hindered by different attitudes and the process of the evaluation, in addition to organisational and other contextual factors. To improve our understanding of the interlinkages in this context, evaluation pathways causally linking different effects and factors are proposed
Faster than light (microscopy): superiority of digital pathology over microscopy for assessment of immunohistochemistry
Get PDFYesDigital pathology offers the potential for significant benefits in diagnostic pathology, but currently the efficiency of slide viewing is a barrier to adoption. We hypothesised that presenting digital slides for simultaneous viewing of multiple sections of tissue for comparison, as in those with immunohistochemical panels, would allow pathologists to review cases more quickly.
Novel software was developed to view synchronised parallel tissue sections on a digital pathology workstation. Sixteen histopathologists reviewed three liver biopsy cases including an immunohistochemical panel using the digital microscope, and three different liver biopsy cases including an immunohistochemical panel using the light microscope. The order of cases and interface was fully counterbalanced. Time to diagnosis was recorded and mean times are presented as data approximated to a normalised distribution.
Mean time to diagnosis was 4 min 3 s using the digital microscope and 5 min 24 s using the light microscope, saving 1 min 21 s (95% CI 16 s to 2 min 26 s; p=0.02), using the digital microscope. Overall normalised mean time to diagnosis was 85% on the digital pathology workstation compared with 115% on the microscope, a relative reduction of 26%.
With appropriate interface design, it is quicker to review immunohistochemical slides using a digital microscope than the conventional light microscope, without incurring any major diagnostic errors. As digital pathology becomes more integrated with routine clinical workflow and pathologists increase their experience of the technology, it is anticipated that other tasks will also become more time-efficient
Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation
No full textYesCoronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency.
One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM.
We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM