50 research outputs found

    Trisubstituted-imidazoles induce apoptosis in human breast cancer cells by targeting the oncogenic PI3K/Akt/mTOR signaling pathway

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    Overactivation of PI3K/Akt/mTOR is linked with carcinogenesis and serves a potential molecular therapeutic target in treatment of various cancers. Herein, we report the synthesis of trisubstituted-imidazoles and identified 2-chloro-3-(4, 5-diphenyl-1H-imidazol-2-yl) pyridine (CIP) as lead cytotoxic agent. Naïve Base classifier model of in silico target prediction revealed that CIP targets RAC-beta serine/threonine-protein kinase which comprises the Akt. Furthermore, CIP downregulated the phosphorylation of Akt, PDK and mTOR proteins and decreased expression of cyclin D1, Bcl-2, survivin, VEGF, procaspase-3 and increased cleavage of PARP. In addition, CIP significantly downregulated the CXCL12 induced motility of breast cancer cells and molecular docking calculations revealed that all compounds bind to Akt2 kinase with high docking scores compared to the library of previously reported Akt2 inhibitors. In summary, we report the synthesis and biological evaluation of imidazoles that induce apoptosis in breast cancer cells by negatively regulating PI3K/Akt/mTOR signaling pathway

    Electrocardiographic findings and prognostic values in patients hospitalised with COVID-19 in the World Heart Federation Global Study

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    BACKGROUND COVID-19 affects the cardiovascular system and ECG abnormalities may be associated with worse prognosis. We evaluated the prognostic value of ECG abnormalities in individuals with COVID-19. METHODS Multicentre cohort study with adults hospitalised with COVID-19 from 40 hospitals across 23 countries. Patients were followed-up from admission until 30 days. ECG were obtained at each participating site and coded according to the Minnesota coding criteria. The primary outcome was defined as death from any cause. Secondary outcomes were admission to the intensive care unit (ICU) and major adverse cardiovascular events (MACE). Multiple logistic regression was used to evaluate the association of ECG abnormalities with the outcomes. RESULTS Among 5313 participants, 2451 had at least one ECG and were included in this analysis. The mean age (SD) was 58.0 (16.1) years, 60.7% were male and 61.1% from lower-income to middle-income countries. The prevalence of major ECG abnormalities was 21.3% (n=521), 447 (18.2%) patients died, 196 (8.0%) had MACE and 1115 (45.5%) were admitted to an ICU. After adjustment, the presence of any major ECG abnormality was associated with a higher risk of death (OR 1.39; 95% CI 1.09 to 1.78) and cardiovascular events (OR 1.81; 95% CI 1.30 to 2.51). Sinus tachycardia (>120 bpm) with an increased risk of death (OR 3.86; 95% CI 1.97 to 7.48), MACE (OR 2.68; 95% CI 1.10 to 5.85) and ICU admission OR 1.99; 95% CI 1.03 to 4.00). Atrial fibrillation, bundle branch block, ischaemic abnormalities and prolonged QT interval did not relate to the outcomes. CONCLUSION Major ECG abnormalities and a heart rate >120 bpm were prognostic markers in adults hospitalised with COVID-19

    The animal breeding abstracts

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    123-130<span style="font-size:12.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:"times="" roman";="" mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:ar-sa"="" lang="EN-US">An account of the coverage, abstracting and editing procedures relating to the publication of the quarterly Animal Breeding Abstracts of the Commonwealth Bureau of Animal Breeding and Genetics is presented.</span

    PIXEL CLASSIFICATION OF SATELLITE IMAGES USING A NOVEL PAIR WISE KERNEL FUNCTION SVM

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    ABSTRACT In this paper we have proposed a symmetric, positive semi definite kernel function for support vector machine classifier. Pixel classification is a form of supervised image segmentation where the actual object classes present in the image are known a priori. In case of satellite image, this prior information plays a huge role to estimate the actual statistics of different land covers. The state of the art kernels have the problem to clearly separate closely spaced data points, as in the case of image pixels of satellite images, where there are no sharp changes between two different regions in terms of the pixel intensity. The proposed kernel has overcome this difficulty with the previous kernels effectively and has good generalization capability. Experimental results establishes the fact when the proposed kernel based SVM has been used for supervised satellite image segmentation purpose

    Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium tuberculosis at Its Bone Marrow Niche

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    One-third of the world&rsquo;s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 &plusmn; 16.3 nm and 84 &plusmn; 18.4 nm, respectively, with the encapsulation efficiency of 69.5% &plusmn; 4.2% and 70.6% &plusmn; 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells

    Demand Response Management of a Residential Microgrid Using Chaotic Aquila Optimization

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    In this paper, Chaotic Aquila Optimization has been proposed for the solution of the demand response program of a grid-connected residential microgrid (GCRMG) system. Here, the main objective is to optimize the scheduling pattern of connected appliances of the building such that overall user cost are minimized under the dynamic price rate of electricity. The GCRMG model considered for analysis is equipped with a fuel cell, combined heat and power (CHP), and a battery storage system. It has to control and schedule the thermostatically controlled deferrable and interruptible appliances of the building optimally. A multipowered residential microgrid system with distinct load demand for appliances and dynamic electricity price makes the objective function complex and highly constrained in nature, which is difficult to solve efficiently. For the solution of such a complex highly constrained optimization problem, both Chaotic Aquila Optimization (CAO) and Aquila optimization (AO) algorithms are implemented, and their performance is analyzed separately. Obtained simulation results in terms of optimal load scheduling and corresponding user cost reveal the better searching and constrained handling capability of AO. In addition, experimental results show that a sinusoidal map significantly improves the performances of AO. Comparison of results with other reported methods are also made, which supports the claim of superiority of the proposed approach

    Impact of Demand Response on Optimal Sizing of Distributed Generation and Customer Tariff

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    Due to the surge in load demand, the scarcity of fossil fuels, and increased concerns about global climate change, researchers have found distributed energy resources (DERs) to be alternatives to large conventional power generation. However, a drastic increase in the installation of distributed generation (DGs) increases the variability, volatility, and poor power quality issues in the microgrid (MG). To avoid prolonged outages in the distribution system, the implementation of energy management strategies (EMS) is necessary within the MG environment. The loads are allowed to participate in the energy management (EM) so as to reduce or shift their demands to non-peak hours such that the maximum peak in the system gets reduced. Therefore, this article addresses the complication of solutions, merits, and demerits that may be encountered in today’s power system and encompassed with demand response (DR) and its impacts in reducing the installation cost, the capital cost of DGs, and total electricity tariff. Moreover, the paper focuses on various communication technologies, load clustering techniques, and sizing methodologies presented

    Impact of Demand Response on Optimal Sizing of Distributed Generation and Customer Tariff

    No full text
    Due to the surge in load demand, the scarcity of fossil fuels, and increased concerns about global climate change, researchers have found distributed energy resources (DERs) to be alternatives to large conventional power generation. However, a drastic increase in the installation of distributed generation (DGs) increases the variability, volatility, and poor power quality issues in the microgrid (MG). To avoid prolonged outages in the distribution system, the implementation of energy management strategies (EMS) is necessary within the MG environment. The loads are allowed to participate in the energy management (EM) so as to reduce or shift their demands to non-peak hours such that the maximum peak in the system gets reduced. Therefore, this article addresses the complication of solutions, merits, and demerits that may be encountered in today&rsquo;s power system and encompassed with demand response (DR) and its impacts in reducing the installation cost, the capital cost of DGs, and total electricity tariff. Moreover, the paper focuses on various communication technologies, load clustering techniques, and sizing methodologies presented
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