Abstract:Gaucher disease (GD) is one of the most common lysosomal storage disorders and is caused by an inherited deficiency in glucocerebrosidase. Dipeptidyl peptidase-4 inhibitors have demonstrated multiple beneficial activities, including anti-diabetic, anti-oxidant, anti-apoptotic, and neuroprotective effects. The aim of this study was to determine if omarigliptin, a dipeptidyl peptidase-4 inhibitor, has a therapeutic effect on fibroblast cells derived from patients with type II GD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of omarigliptin on cell viability. The expression patterns of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of omarigliptin treatment on GD cells. Thin-layer chromatography (TLC) was performed to determine glucosylceramide levels in omarigliptin-treated GD cells. Omarigliptin increased GD cell viability compared to untreated control cells. Further, omarigliptin treatment dose-dependently decreased the apoptotic factors AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of intracellular glucosylceramides in omarigliptin-treated GD cells. These findings demonstrate that omarigliptin can reduce cellular stress resulting from glucosylceramide accumulation, and suggest that omarigliptin should be studied further as a novel therapeutic agent for GD.
Abstract:Gaucher disease is the most common lysosomal storage disorder. Resveratrol is a phytoalexin that possesses a wide range of beneficial effects, including anti-inflammatory, anti-oxidant, and neuroprotective properties. This study was conducted to determine whether the resveratrol derivative HG-101 has a therapeutic effect on primary fibroblast cells derived from patients with type III Gaucher disease. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of HG-101 on cell survival. The expression levels of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of HG-101 treatment on Gaucher disease cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in HG-101-treated patient cells. HG-101 increased the viability of patient cells compared to that of untreated control cells. HG-101 treatment dose-dependently decreased AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of glucosylceramides in HG-101-treated patient cells. These findings demonstrate that the resveratrol derivative HG-101 can relieve cellular stress due to glucosylceramide accumulation, and suggest that it should be studied further as a new therapeutic approach for the treatment of neuronopathic Gaucher disease.
Abstract:Gaucher disease (GD) is the most prevalent lysosomal storage disorder caused by an inherited deficiency of glucocerebrosidase. In the present study, we aimed to determine whether dipeptidyl peptidase-4 inhibitors (DPP4i) exhibit a potential therapeutic effect in type I GD cells. Four kinds of DPP4i were tested in dermal fibroblasts from patients with type I GD. MTT assays were performed to determine their effects on cell viability. The expression levels of Bcl-2-associated X protein (Bax), ATP-citrate synthase (ATP-CS), E3-binding protein (E3BP), and acetyl-coenzyme A acetyltransferase 1 (ACAT1) were determined by western blotting to understand the molecular mechanism of DPP4i in cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in cultured fibroblasts. This investigation showed that DPP4i increased cell viability more than 1.45 times. After exposure to DPP4i, the expression level of Bax decreased, whereas those of ATP-CS, E3BP, and ACAT1 increased. TLC revealed reduced amounts of intracellular glucosylceramides in type I GD patient cells. Here, we suggest that DPP4i can reduce cellular stress by glucosylceramide accumulation, and that it may be utilized as a new therapeutic approach for Gaucher disease.
Abstract:We consider estimation problems for linear systems with random matrices and additive uncertain disturbances. Information sets containing true states of the systems are defined and investigated. The sets are described by its support functions. Some theorems\non the approximation of the sets by be simpler objects are given. Particular cases, where matrices of the systems or probability spaces have special formes, are elaborated. In conclusion we review some examples.
Abstract:We introduce a binary coding system to represent integers, and call it the Golden system.\nThe Golden system supports the increment and decrement of a digit at arbitrary position by performing at most two bit flips.\nCounting up or down can then be performed in a constant time such that every successive pair of numbers differ in at most two bits.\nThe addition and subtraction of two integers can be performed in a number of bit operations and time proportional to the length of the shorter number, not the longer as in the case of the ordinary binary and decimal systems.\nThis may lead to significant speed-ups in computer hardware design and in many software applications.
Abstract:Fermatean fuzzy set (FFS) is the generalization of both intuitionistic\nfuzzy set (IFS) and Pythagorean fuzzy set (PFS). FFS possesses higher\nprospect of applications because of its wider scope compare to IFS and PFS.\nThe notion of composite relation is a very important information measure in\ndetermining decision-making problems, and thus this paper proposes max-minmax\ncomposite relation under Fermatean fuzzy environment and discusses some\nproperties of FFS. We present an algorithm with its flowchart to aid the computation of Fermatean fuzzy max-min-max composition (FFMMMC). In terms\nof application, a hypothetical medical diagnostic reasoning is determined based\non the proposed FFMMMC where diseases and patients are presented as Fermatean\nfuzzy values in the feature space of some symptoms.
Abstract:The Instrumentation Amplifier is among the most critical components of an ECG recording device. The Instrumentation Amplifier may have been the first component in the analog chain to analyze the ECG data from the human body, determining crucial ECG system parameters including noise and CMRR. Owing to the ECG\'s very limited bandwidth, developing a fully integrated ECG recording system is extremely difficult.This article discusses a concept for a completely integrated instrumentation amplifier with low noise & low power consumption. The Instrumentation Amplifier\'s operational power consumption block is just an Operational Transconductance Amplifier (OTA), that leads in minimal power consumption. The current mirror-based low power OTA was developed in this study using MOSFET sub threshold concept. The circuit\'s transistors are configured to operate throughout the weak inversion region. CMOS 45nm technology is used to develop and simulate the circuit. With 1V supply voltage, the proposed IA has an input referred noise of 1.21 μVrms.
Abstract:Tuberculosis is a deadly disease, being responsible for management challenges. It is estimated there are about 9 million people engaged to tuberculosis every year. By 2020, there are expectedly additional 200 million infected cases and 70 million deaths caused by tuberculosis. The most effective treatment for tuberculosis - pleural puncture chemotherapy - is subject to effusion complications within 6-8 months, which has been a major obstacle in controlling tuberculosis for a long time. Therefore, it is essential to invent new drugs or work out new treatment methods to shorten the treatment course. Meanwhile, the method using low-level laser as a mean to support tuberculosis treatment has been widely researched. The article applies research on semiconductor laser created in tuberculosis treatment. Monte Carlo simulation method is used to irradiate low-power semiconductor laser beam to pulmonary tissues on the front and back chest of the patient, to select the suitable wavelength for the research and application of low-level semiconductor laser in supporting the treatment of tuberculosis in the community.
Abstract:In the Fourth Industrial Revolution, crime is hardly reported to the Police, or other law enforcement agencies. Most victims prefer to go on social media and vent, as this medium is easier for them to access and requires no paperwork or interrogations. This leaves policy makers and the law enforcement with skewed dataset, due to unreported crimes. Hence, it is paramount that one finds a way to “mine” the crime data reported on social media to comprehensively gain insights in crimes that have been committed for decision making. In this paper, we have attempted to estimate crime rates, using one microblogging and social networking service, Twitter as a data source. To do this, we have used a formal technique – Jumping Finite Automata (JFA), for the abstraction of a corpus of crime-related words and leveraged shuffle algorithms to establish semantic relationships between these words. Furthermore, we implemented JFA in a tool called “Crime-Ripper”. Through evaluation, we demonstrate that given real-world tweet dataset, Crime-Ripper is able to estimate crime rates and produce reports that are map annotations, showing areas of a city and their respective estimated crime-rates. Crime-Ripper is expected to find applications in law enforcement, policy making and public safety sensitization.
Abstract:Technological advancement has diversified advertising into a multi-faceted and dynamic channel with enormous growth and prospects. Marketing data of today requires big data analytics to predict trends necessary for decision making. This work is inspired by the signaling theory and used 23589 datasets drawn from three global B2C and C2C websites using the scrappy web crawler. Using the serial moderated mediation analysis, we investigate a resilience model in the relationship between short video advertising (SV) adoption, quality signals, customer satisfaction, price fairness, and sales in digital marketing. With price as a moderator, SVs significantly affect sales while controlling for logistics service quality, location, and product categories. Quality signals and customer satisfaction are found to have significant mediation powers on the relationship short video ads have on sales. Price has a positive moderating effect on quality signals but a negative impact on customer satisfaction. Whereas shop location is vital in traditional shopping, logistics service quality overrides its influence in online shopping settings. We made a significant effort to identify actual online data to justify why SV adoption is essential in e-commerce and digital marketing. E-vendors can now leverage this to focus on what matters.