1,721,073 research outputs found
Silver nitroprusside as an efficient chemodynamic therapeutic agent and a peroxynitrite nanogenerator for targeted cancer therapies
No full textIntroduction
Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species. However, CDT is limited by the lower amount of catalyst ions that can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome.
Objectives
To overcome these limitations, a tailored approach, which utilizes dual metals cations (Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kill cancer cells by taking advantage of tumor acidic environment without used of any external stimuli.
Methods
A simple solution mixing procedure was used to synthesize AgNP as CDT agent. AgNP were structurally and morphologically characterized, and it was observed that a minimal dose of AgNP is required to destroy cancer cells with limited effects on normal cells. Moreover, comprehensive in vitro studies were conducted to evaluate antitumoral mechanism.
Results
AgNP have an effective ability to decompose endogenous H2O2 in cells. The decomposed endogenous H2O2 generates several different types of reactive species (•OH, O2•−) including peroxynitrite (ONOO−) species as apoptotic inducers that kill cancer cells, specifically. Cellular internalization data demonstrated that in short time, AgNP enters in lysosomes, avoid degradation and due to the acidic pH of lysosomes significantly generate high ROS levels. These data are further confirmed by the activation of different oxidative genes. Additionally, we demonstrated the biocompatibility of AgNP on mouse liver and ovarian organoids as an ex vivo model while AgNP showed the therapeutic efficacy on patient derived tumor organoids (PDTO).
Conclusion
This work demonstrates the therapeutic application of silver nitroprusside as a multiple ROS generator utilizing Fenton like reaction. Thereby, our study exhibits a potential application of CDT against HGSOC (High Grade Serous Ovarian Cancer), a deadly cancer through altering the redox homeostasis
Controlled, partially exfoliated, self-supported functionalized flexible graphitic carbon foil for ultrasensitive detection of SARS-CoV-2 spike protein
Full text linkThis paper reports on an ultrasensitive and label-free electrochemical immunosensor for monitoring the SARSCoV-2 spike protein (SARS-CoV-2 SP). A self-supported electrode, which can simultaneously serve as an antibody immobilization matrix and electron transport channel, was initially fabricated by a controlled partial exfoliation of a flexible graphitic carbon foil (GCF). Mild acidic treatment enabled the partial oxidation and exfoliation (down to a few layers) of the flexible GCF; this also provided a high percentage of oxygen functionality and an enhanced surface roughness. The substrate electrode was further functionalized with ethylenediamine (EDA) to provide a suitable platform with even a higher surface roughness, for the covalent immobilization of an anti-SARS-CoV-2 antibody. The change in the current response for the [Fe(CN)(6)](3-/4-) redox couple, induced by the binding of SARS-CoV-2 SP to the antibody immobilized on the electrode surface, was used to determine the SARS-CoV-2 SP concentration. The immunosensor thus prepared could detect SARSCoV-2 SP within 30 min with high reproducibility and specificity over a wide concentration range (0.2-100 ng/ mL). Detection limits of 25 pg/mL and 27 pg/mL were found in a phosphate buffer solution (pH 7.4), and diluted blood plasma, respectively. The immunosensor was also employed to detect SARS-CoV-2 SP in artificial human saliva
Iron nitroprusside as a chemodynamic agent and inducer of ferroptosis for ovarian cancer therapy
Full text linkChemoDynamic Therapy (CDT) is a powerful therapeutic modality using Fenton/Fenton-like reactions to produce oxidative stress for cancer treatment. However, the insufficient amount of catalyst ions and ROS scavenging activity of glutathione peroxidase (GPX4) limit the application of this approach. Therefore, a tailored strategy to regulate the Fenton reaction more efficiently (utilizing dual metal cations) and inhibit the GPX4 activity, is in great demand. Herein, a CDT system is based on dual (Fe2+ metals) iron pentacyanonitrosylferrate or iron nitroprusside (FeNP) having efficient ability to catalyze the reaction of endogenous H2O2 to form highly toxic OH species in cells. Additionally, FeNP is involved in ferroptosis via GPX4 inhibition. In particular, FeNP was structurally characterized, and it is noted that a minimum dose of FeNP is required to kill cancer cells while a comparable dose shows negligible toxicity on normal cells. Detailed in vitro studies confirmed that FeNP participates in sustaining apoptosis, as determined using the annexin V marker. Cellular uptake results showed that in a short time period, FeNP enters lysosomes and, due to the acidic lysosomal pH, releases Fe2+ ions, which are involved in ROS generation (OH species). Western blot analyses confirmed the suppression of GPX4 activity over time. Importantly, FeNP has a therapeutic effect on ovarian cancer organoids derived from High-Grade Serous Ovarian Cancer (HGSOC). Furthermore, FeNP showed biocompatible nature towards normal mouse liver organoids and in vivo. This work presents the effective therapeutic application of FeNP as an efficient Fenton agent along with ferroptosis inducer activity to improve CDT, through disturbing redox homeostasis
Islamic activism in Bangladesh: a case study of the Jamaat-e-Islami Bangladesh, 2007
No full textThis dissertation is a study of the dynamics and direction of contemporary Islamic activism. It examines why some Muslims turn to Islamic activism and what determines the direction of this movement. It focuses on the Jamaat-e-Islami of Bangladesh, one of the most influential Islamic activist movements in South Asia. The study particularly explores the factors that contributed to the rise of the Jamaat-e-Islami in Bangladesh, and the subsequent transformation of this movement. The basic premise of this study is that the appeal of the contemporary Islamic activism is primarily religious, but wherever and whenever it participates in a democratic system, moderation is critical to its wider appeal and political success. By examining the historical roots, ideological discourse, organizational mechanism and the strategy of the Jamaat-e-Islami based on both primary and secondary source materials, the study uncovers that while at the core of this movement is a religious reawakening and rhetoric that were generated by new kind of Islamic discourses and sustained by a well-knit organizational network, this awakening being the result of one particular reading of Islam has attracted only a limited number of adherents. Having failed to win the hearts and minds of the majority as reflected in repeated electoral showings, the Jamaat has turned to redefine its ideology and socio-political agenda by adopting a pragmatic and relatively liberal approach in the political arena. While it is still experiencing dilemmas in reconciling and re-interpreting much of its agenda, the transformation the party has gone through in Bangladesh is significant, for it demonstrates its flexible character and a trend toward further moderation. Empirical findings of this study have wider theoretical implications. First, contemporary Islamic movements are not necessarily fundamentalist, reactive or radical, as they are often portrayed in the literature of this subject. In contrast, this study finds that while a degree of nostalgia is at work in Islamic activism in that it often refers back to the early history of Islam, it nevertheless embraces modernity. Second, this study unveils the diverse character of the Islamic activism that can be radical as well as moderate. It also shows that the character of an Islamic movement is shaped not just by a particular reading of Islam, but also by the context in which it operates. In other words, the nature of contemporary Islamic activism is largely contextual. Third, the ideological position and character of Islamic movements are still evolving. Fourth (and finally), pluralist democracy helps moderate the character of an Islamic movement, especially when the latter becomes the part of this process
Label-free electrochemical aptasensor for the detection of SARS-CoV-2 spike protein based on carbon cloth sputtered gold nanoparticles
Full text linkThe proliferation and transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or the (COVID-19) disease, has become a threat to worldwide biosecurity. Therefore, early diagnosis of COVID-19 is crucial to combat the ongoing infection spread. In this study we propose a flexible aptamer-based electrochemical sensor for the rapid, label-free detection of SARS-CoV-2 spike protein (SP). A platform made of a porous and flexible carbon cloth, coated with gold nanoparticles, to increase the conductivity and electrochemical performance of the material, was assembled with a thiol functionalized DNA aptamer via S–Au bonds, for the selective recognition of the SARS-CoV-2 SP. The various steps for the sensor preparation were followed by using scanning electron microscopy, cyclic voltammetry and differential pulse voltammetry (DPV). The proposed platform displayed good mechanical stability, revealing negligible changes on voltammetric responses to bending at various angles. Quantification of SARS-CoV-2 SP was performed by DPV and chronopotentiometry (CP), exploiting the changes of the electrical signals due the [Fe(CN)6]3-/4- redox probe, when SARS-CoV-2 SP binds to the aptamer immobilized on the electrode surface. Current density, in DPV, and square root of the transition time, in CP, varied linearly with the log[ SARS-CoV-2 SP], providing lower limits of detection (LOD) of 0.11 ng/mL and 37.8 ng/mL, respectively. The sensor displayed good selectivity, repeatability, and was tested in diluted human saliva, spiked with different SARS-CoV-2 SP concentrations, providing LODs of 0.167 ng/mL and 46.2 ng/mL for DPV and CP, respectively
Self-Therapeutic Cobalt Hydroxide Nanosheets (Co(OH)2 NS) for Ovarian Cancer Therapy
Full text linkHigh-grade serous ovarian cancer (HGSOC) is one of the major life-threatening cancers in women, with a survival rate of less than 50%. So far, chemotherapy is the main therapeutic tool to cure this lethal disease; however, in many cases, it fails to cure HGSOC even with severe side effects. Self-therapeutic nanomaterials could be an effective alternative to chemotherapy, facilitated by their diverse physicochemical properties and the ability to generate reactive species for killing cancer cells. Herein, inorganic cobalt hydroxide nanosheets (Co(OH)2 NS) were synthesized by a simple solution process at room temperature, and morphological, spectroscopic, and crystallographic analyses revealed the formation of Co(OH)2 NS with good crystallinity and purity. The as-prepared Co(OH)2 NS showed excellent potency, comparable to the FDA-approved cisplatin drug to kill ovarian cancer cells. Flow cytometric analysis (nnexin V) revealed increased cellular apoptosis for Co(OH)2 NS than cobalt acetate (the precursor). Tracking experiments demonstrated that Co(OH)2 NS are internalized through the lysosome pathway, although relocalization in the cytoplasm has been observed. Hence, Co(OH)2 NS could be an effective self-therapeutic drug and open up an area for the optimization of self-therapeutic properties of cobalt nanomaterials for cancer treatment
Challenges and Strategies to Conduct Research at Restricted Rohingya Refugee Camps of Bangladesh
No full textAbstract: Rohingya refugees have been living in Bangladesh for decades. Before the latest 2017 exodus only two registered camps and some unregistered spots lying with the registered camps were present in the Cox’s Bazar area of Bangladesh. However, now 33 makeshift camps are hosting around one million Rohingyas coming from Myanmar. The government of Bangladesh prohibits visitors’ access in those camps without prior official permission. The bureaucratic hurdles for securing permission from the respective office to get into the camps are lengthy, difficult and time consuming. Besides research in any humanitarian settings like Rohingya camps having vulnerable communities require some special ethical consideration. This paper draws fieldwork experiences among the makeshift camps of Cox’s Bazar, Bangladesh. It sheds light on practical experience and challenges in the field and the required strategies taken by the author to do a productive fieldwork overcoming all the challenge
Improving the crown rot resistance and tolerance of wheat using marker-assisted recurrent selection
Full text linkCrown rot disease (Fusarium pseudograminearum) of wheat causes significant yield losses across Australia. However, the genetic control of crown rot resistance and tolerance is complex and traditional breeding strategies have proven ineffective. Marker Assisted Recurrent Selection (MARS) was examined as a strategy to more effectively pyramid the many minor genes controlling plant response to crown rot. Populations were developed from three-way crosses to (i) optimize screening procedures for crown rot, (ii) examine the relationship between resistance and tolerance, (iii) identify quantitative trait loci (QTL) linked to resistance and tolerance, (iv) pyramid QTLs using MARS and (v) confirm response to selection. Disease severity in greenhouse pot tests was less reliable than field screening using managed inoculum; hence field screening was used for all subsequent evaluations. In the MARS approach, materials from each population were genotyped and phenotyped by F4 for crown rot response and QTLs linked to crown rot resistance and/or tolerance identified. Consistent QTL, mapped to unique chromosomal regions, were then recombined in crossing to pyramid markers. Following two cycles of recombination, the progeny from both cycles of MARS, the base population and the original parents were compared for resistance and/or tolerance depending on the population. Resistance and tolerance (determined as reduced yield loss in the presence of crown rot) were independently inherited. A significant and positive response to selection was observed with some recombinants significantly more resistant and higher yielding than their parents. The genotypes identified and developed in this study combine multiple sources of resistance and tolerance and these materials and their associated markers can be used by the Australian wheat industry to improve wheat yield in the presence of crown rot
Solving Multi-Objective Assignment Problem with Decision Maker’s Preferences by Using Genetic Algorithm
No full textThis thesis is submitted to the Department of Mechanical Engineering, Khulna University of Engineering & Technology in partial fulfillment of the requirements for the degree of Master of Science in Mechanical Engineering, June 2019.Cataloged from PDF Version of Thesis.Includes bibliographical references (pages 43-45).The multi-objective assignment problem is basically the N men –N tasks problem, where a single task has to be assigned to an individual with a view of optimizing the outcomes. A common challenge is to address the conflicting objectives which produce Pareto–optimal solutions. The main feature of the work is- normalizing all the criteria into a single scale regardless of their measurement units and their demand of minimum or maximum, which reliefs the researchers from careful attention in quantifying the quality criteria. The methodology also included the decision maker’s preferences regarding the objectives. While solving the problem through a genetic algorithm, a new encoding scheme is used together with a partially matched crossover (PMX). The working principle of the proposed algorithm is illustrated with a numerical example and its effectiveness has been compared with some well-established methodologies. It is found that the proposed algorithm provides a better solution with minimal computational effort.Md. Mahbubur RahmanMaster of Science in Mechanical Engineerin
Low-Power Wide-Area Network Design
Full text linkLow-Power Wide-Area Network (LPWAN) is an enabling technology for long-range, low-power, and low-cost Internet of Things (IoT) and Cyber-Physical Systems (CPS) applications. Due to their escalating demand in the IoT/CPS applications, recently, multiple LPWAN technologies have been developed that operate in the cellular/licensed (e.g., 5G, LTE Cat M1, and NB-IoT) and unlicensed/ISM (e.g., LoRa and SigFox) bands. To avoid the crowd in the limited ISM band (where most LPWANs operate) and the cost of the licensed band, we propose a novel LPWAN technology called Sensor Network Over White Spaces (SNOW) by utilizing the TV white spaces. White spaces refer to the allocated but locally unused TV channels (54--698MHz in the US) and can be used by the unlicensed devices as secondary users. White spaces offer less crowded and much wider spectrum in both urban and rural areas, boasting an abundance in rural and suburbs and have excellent propagation and obstacle penetration characteristics that enable long-range communication.
In this thesis, we design, develop, and experiment SNOW that is highly scalable, energy-efficient, and can connect thousands of sensors over a single-hop distance of several kilometers. SNOW achieves scalability and energy efficiency by enabling concurrent packets reception (Rx) at a base station (BS) using a single radio from numerous sensors and concurrent packets transmission (Tx) to numerous sensors from the BS using a single radio, simultaneously, which we achieve by proposing a distributed implementation of Orthogonal Frequency Division Multiplexing. We also demonstrate the feasibility of SNOW design by implementing on a prototype hardware called Universal Software Radio Peripheral(USRP).
To enable the low-cost and scalable SNOW deployment in practical IoT/CPS applications, we then implement SNOW using the low-cost and small form-factored commercial off-the-shelf (COTS) devices, where we address multiple practical challenges including the peak-to-average power ratio (PARP) problem handling, channel state information estimation, and carrier frequency offset estimation. Additionally, we propose an adaptive transmission power protocol for the SNOW nodes to handle the near-far power problem in SNOW. To demonstrate the feasibility of COTS SNOW implementation, we use TI CC1310 and TI CC1350 devices as SNOW nodes and deploy in the city of Detroit, Michigan.
To enable connecting tens of thousands of nodes over hundreds of kilometers, we further propose a network architecture called SNOW-tree through a seamless integration of multiple SNOWs where they form a tree structure and are under the same management/control at the tree root. We address the intra-SNOW and inter-SNOW interferences in SNOW-tree by formulating a constrained optimization problem called the scalability optimization problem (SOP) whose objective is to maximize scalability by managing the spectrum sharing across the SNOWs. By proving the NP-hardness of SOP, we then propose two polynomial-time methods to solve it: a greedy heuristic algorithm and a 1/2-approximation algorithm. Our deployment covering approximately (25x15)sq. km in the Detroit metropolitan area demonstrates that both of our algorithms are highly efficient in practice
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