Rational design and robust formulation processes are critical for optimal delivery of mRNA by lipid nanoparticles (LNPs). Varying degrees of heterogeneity in mRNA-LNPs can affect their biophysical ...and functional properties. Given the profound complexity of mRNA-LNPs, it is critical to develop comprehensive and orthogonal analytical techniques for a better understanding of these formulations. To this end, we developed a robust ultracentrifugation method for density-based separation of subpopulations of mRNA-LNPs. Four LNP formulations encapsulating human erythropoietin (hEPO) with varying functionalities were synthesized using two ionizable lipids, A and B, and two helper lipids, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and 1,2-dierucoyl-sn-glycero-3-phosphoethanolamine (DEPE), along with cholesterol and DMG-PEG-2K. Upon ultracentrifugation on a sucrose gradient, a distinct pattern of “fractions” was observed across the gradient, from the less dense topmost fraction to the increasingly denser bottom fractions, which were harvested for comprehensive analyses. Parent LNPs, A-DOPE and B-DOPE, were resolved into three density-based fractions, each differing significantly in the hEPO expression following intravenous and intramuscular routes of administration. Parent B-DEPE LNPs resolved into two density-based fractions, with most of the payload and lipid content being attributed to the topmost fraction compared to the lower one, indicating some degree of heterogeneity, while parent A-DEPE LNPs showed remarkable homogeneity, as indicated by comparable in vivo potency, lipid numbers, and particle count among the three density-based fractions. This study is the first to demonstrate the application of density gradient-based ultracentrifugation (DGC) for a head-to-head comparison of heterogeneity as a function of biological performance and biophysical characteristics of parent mRNA-LNPs and their subpopulations.
Therapeutic approaches for the induction of immune tolerance remain an unmet clinical need for the treatment of autoimmune diseases, including multiple sclerosis (MS). Based on its role in the ...control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is a candidate target for novel immunotherapies. Here, we report the development of AhR-activating nanoliposomes (NLPs) to induce antigen-specific tolerance. NLPs loaded with the AhR agonist ITE and a T cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 induced tolerogenic dendritic cells and suppressed the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, in preventive and therapeutic setups. EAE suppression was associated with the expansion of MOG35–55-specific FoxP3⁺ regulatory T cells (Treg cells) and type 1 regulatory T cells (Tr1 cells), concomitant with a reduction in central nervous system-infiltrating effector T cells (Teff cells). Notably, NLPs induced bystander suppression in the EAE model established in C57BL/6 × SJL F1 mice. Moreover, NLPs ameliorated chronic progressive EAE in nonobese diabetic mice, a model which resembles some aspects of secondary progressive MS. In summary, these studies describe a platform for the therapeutic induction of antigen-specific tolerance in autoimmune diseases.
Electronic waste is an increasing issue and a serious pollution problem for the environment and human life. The disposal of electronic waste is becoming a serious problem. The main potential for ...addressing the disposal of large amounts of electronic waste material is in the construction industry. The excess cost of coarse aggregate has forced civil engineers to find out an alternative solution for the construction materials. So, we can use e-waste as a partial replacement for coarse aggregate. Using electronic waste in construction will not only reduce the waste materials like electronic waste from the earth but also reduce the construction material(concrete) that will lead to economic construction. for Concrete mixes, different rate percentages of E-waste were selected and three different types of conventional and standard specimens have been decided to be partly replaced by E-waste at a percentage rate of 10%, 20%, and 30% for a coarse aggregate. M25 Concrete is usually prepared for conventional specimens without using E-waste aggregates. The results and effectiveness of concrete with e-waste replacement and the physical and mechanical properties of the following have been studied in this paper.
Emotions are sudden rushes; they are unexpected factors dependent on the living situations. Generally, there are two types of emotions: positive and negative. The most impactful emotions are the ...negative ones. Nowadays, depression has become a common disorder. But seeking professional help isn't something everyone can afford. To overcome this, many people go through different therapies. Music therapy is the most common type and it helps calm the nerves affected due to social pressure, anxiety, depression etc. In recent era, the interaction between machine and human has become very convenient. Therefore, we have proposed a speech emotion recognition-based framework for a music therapy suggestion system using machine learning. Three emotion classes considered are happy, angry and depressed. Experimentation is carried out on the English language RAVDESS Dataset, augmented RAVDESS dataset, and combined dataset. With the SVM classifier and PCA feature selection algorithm average accuracy for RAVDESS 80.21%, for an augmented dataset 98.09%, while that for Combination (RAVDESS + Augmented) an accuracy of 91.11% is obtained.
A WebRTC Based Video Conferencing System with Screen Sharing Kasetwar, Abhay; Balani, Nikita; Damwani, Deepika ...
International Journal for Research in Applied Science and Engineering Technology,
5/2022, Letnik:
10, Številka:
5
Journal Article
Odprti dostop
With the modern and rapid development of the internet, people's connections are more important than ever, and they're looking for new ways to communicate with one another in real time. WebRTC is a ...futuristic technology that enables realtime communication in audio, video, and data transmission through web browsers without the need for a plugin by using JavaScript APIs (Application Programming Interface). In this paper, we present a web peer-to-peer real-time communication system that allows users to communicate across a communication channel with high-speed data transmission using WebRTC technology, HTML5, and a Node.js server address. The outcome demonstrates that the system is stable, fully functioning, and secure. Keywords: WebRTC, Vide o Conferencing Application, Peer to Peer
Policies and distinct steps are taken by nations facing water shortages such as India, China and Middle East Asia. The demand control techniques are identified with growing population and increased ...demand for food, water and insufficient supplies. As a profitable renewable water supply, Simulated Water has been embraced. Virtual Water must be treated as the need of the hour with Advanced Water Supply Management (IWRM). The Virtual Water Trade (VWT) is the concept when commodities and services are exchanged, so is VW. When a country imports one ton of wheat instead of producing in its own country, it is saving about 1,300 cubic meters of real water. If this country is facing water crisis, the water that is 'saved' can be used for other means. VW can be stated as water that is used for producing a commodity, not in the real sense, but in a virtual sense. The term virtual refers to the fact that at the end, the water which is not contained in the final product is the VW, also known as 'embedded water'. External water is thus added on to a country 's 'internal water'. For the quantitative definition of VW, principally two different approaches are proposed and applied till date. In one approach, the VW content is defined as the quantity of water that was used to produce any commodity. It depends on certain conditions, including place, time of production & water usage and its efficiency. Producing 1 kg of grains in a dry region requires 2 or 3 times more water than producing the same quantity in a humid region. In the second approach producer's perspective is taken, and here VW is defined as the content of commodity where the quantity of water that might be required to produce the good at the required place is considered. This is especially important if the question is posed: what quantity of water can one save if one imports a commodity rather than producing it oneself? One relevant concept that is associated with VW is the 'water footprint '. The worth of VW as an alternate water resource is extremely important basically for water short nations. This paper focuses on concept of worldwide VW trade. The paper emphasizes on analysing global status of V.W.T. & implementation of V.W.T at National & State level in India. This research concluded that, after studying the worldwide scope of V.W.T there's an opportunity for the appliance of the VW concept at the national level and at state level taking under consideration, water endowments, and other natural and social economic conditions. We 've also examined the worldwide statues of V.W.T across different nations and have located some essential factors required for successful V.W.T in importing counties. The VW trade seeks ways to consciously and efficiently utilize the internal and external water sources to alleviate water crises. Research also shows that V.W.T is already being practiced at an inter-state level in India.
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