Duality of iron as an essential cofactor of many enzymatic metabolic processes and as a catalyst of poorly controlled redox-cycling reactions defines its possible biological beneficial and hazardous ...role in the body. In this review, we discuss these two “faces” of iron in a newly conceptualized program of regulated cell death, ferroptosis. Ferroptosis is a genetically programmed iron-dependent form of regulated cell death driven by enhanced lipid peroxidation and insufficient capacity of thiol-dependent mechanisms (glutathione peroxidase 4, GPX4) to eliminate hydroperoxy-lipids. We present arguments favoring the enzymatic mechanisms of ferroptotically engaged non-heme iron of 15-lipoxygenases (15-LOX) in complexes with phosphatidylethanolamine binding protein 1 (PEBP1) as a catalyst of highly selective and specific oxidation reactions of arachidonoyl- (AA) and adrenoyl-phosphatidylethanolamines (PE). We discuss possible role of iron chaperons as control mechanisms for guided iron delivery directly to their “protein clients” thus limiting non-enzymatic redox-cycling reactions. We also consider opportunities of loosely-bound iron to contribute to the production of pro-ferroptotic lipid oxidation products. Finally, we propose a two-stage iron-dependent mechanism for iron in ferroptosis by combining its catalytic role in the 15-LOX-driven production of 15-hydroperoxy-AA-PE (HOO-AA-PE) as well as possible involvement of loosely-bound iron in oxidative cleavage of HOO-AA-PE to oxidatively truncated electrophiles capable of attacking nucleophilic targets in yet to be identified proteins leading to cell demise.
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•Phospholipid peroxidation in ferroptosis.•Lipoxygenase oxidation of arachidonoyl phosphatidylethanolamine.•Guided transportation of iron to target destinations in cells.•GPX4 reduction of hydroperoxy-arachidonoyl-phosphatidylethanolamine.•ACSL4 biosynthesis of arachidonoyl phosphatidylethanolamine is required for.
With the integration of Wireless Sensor Networks and the Internet of Things, the smart grid is being projected as a solution for the challenges regarding electricity supply in the future. However, ...security and privacy issues in the consumption and trading of electricity data pose serious challenges in the adoption of the smart grid. To address these challenges, blockchain technology is being researched for applicability in the smart grid. In this paper, important application areas of blockchain in the smart grid are discussed. One use case of each area is discussed in detail, suggesting a suitable blockchain architecture, a sample block structure and the potential blockchain technicalities employed in it. The blockchain can be used for peer-to-peer energy trading, where a credit-based payment scheme can enhance the energy trading process. Efficient data aggregation schemes based on the blockchain technology can be used to overcome the challenges related to privacy and security in the grid. Energy distribution systems can also use blockchain to remotely control energy flow to a particular area by monitoring the usage statistics of that area. Further, blockchain-based frameworks can also help in the diagnosis and maintenance of smart grid equipment. We also discuss several commercial implementations of blockchain in the smart grid. Finally, various challenges to be addressed for integrating these two technologies are discussed.
The growth restriction factor
Q is the key quantity in current descriptions of the solutal effect on grain growth and grain refinement during solidification of alloys. A rigorous treatment for the ...evaluation of
Q in multicomponent alloys based on consistent thermodynamic descriptions of the alloy phase equilibria is presented. On closer inspection the conventional approach to calculate
Q in multicomponent alloys from liquidus gradient
m
i and partition coefficient
k
i must fail for a wide range of common alloys exhibiting minute amounts of primary crystallizing intermetallic phase, exemplified for Mg–Al–Mn and Al–Si–Ti alloys. The rigorous approach provides an extension of the applicability range of the concept of
Q. The qualitative similarity of inoculant particles and primary intermetallic phases is verified by calculations for Al–Si–Ti–B alloys.
To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of
, or evolution by tumor neofunctionalization, has been developed. The important demand for ...a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using
theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (
genes). (3) Human orthologs of fish
genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that
theory has predictive power, fulfilling a fundamental requirement for a new theory.
Ethanol is an attractive alternative fuel because it is a renewable bio-based resource and it is oxygenated, thereby providing the potential to reduce particulate emissions in compression-ignition ...engines. Thus, the use of ethanol in a diesel engine can simultaneously solve two important problems - the replacement of non-renewable diesel fuel and improving the environmental performance of diesel by reducing soot emissions into the atmosphere. Thus, the use of ethanol in a diesel engine can simultaneously solve two important problems - the replacement of non-renewable diesel fuel and improving the environmental performance of diesel by reducing soot emissions into the atmosphere. The presented work considers the main reasons for reducing the formation of solid particles in the diesel cylinder, taking into account the transformation of the combustion process. The article presents the results of experimental studies to reduce the soot content in the exhaust gases by direct injection of ethanol into the combustion chamber with ignition from the burning fuel jet. The implementation of this method somewhat complicates the design of the diesel engine but allows you to control the combustion process and exclude the maximum amount of diesel fuel. The characteristics of the combustion process of alternative fuels in the diesel cylinder and the main patterns of change are described. In conclusion, the main problems of the use of ethanol and promising directions of its use as a fuel for the engine with compression ignition are considered, taking into account the peculiarities of the combustion process and the formation of harmful components of exhaust gases.
In previous publications, the author developed the theory of carcino-evo-devo, which predicts that evolutionarily novel organs should recapitulate some features of tumors in their development.
...Mammalian adipose is currently recognized as a multi-depot metabolic and endocrine organ consisting of several adipose tissues. Although lipid-storing cells and proteins are ancient, the adipose organ as a whole is evolutionarily novel to mammals. The adipose expansion has remarkable similarities with the growth of solid tumors. These similarities are the following: (1) The capability to unlimited expansion; (2) Reversible plasticity; (3) Induction of angiogenesis; (4) Chronic inflammation; (5) Remodeling and disfunction; (6) Systemic influence on the organism; (7) Hormone production; (8) Production of miRNAs that influence other tissues; (9) Immunosuppression; (10) DNA damage and resistance to apoptosis; (11) Destructive infiltration in other organs and tissues. These similarities include the majority of "hallmarks of cancer". In addition, lipomas are the most frequent soft tissue tumors, and similar drugs may be used for the treatment of obesity and cancer by preventing infiltration. This raises the possibility that obesity, at least in part, may represent an oncological problem. The existing similarities between adipose and tumors suggest the possible evolutionary origin of mammalian adipose from some ancestral benign mesenchymal hereditary tumors. Indeed, using a transgenic inducible zebrafish tumor model, we described many genes, which originated in fish and were expressed in fish tumors. Their human orthologs LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA acquired functions connected with the adipose organ. They are also involved in tumor development in humans.
If the hypothesis of the evolutionary origin of the adipose organ from the ancestral hereditary tumor is correct, it may open new opportunities to resolve the oncological problem and the problem of the obesity epidemic. New interventions targeting LEP, NOTCH1, SPRY1, PPARG, ID2, and CIDEA gene network, in addition to what already is going on, can be designed for treatment and prevention of both obesity and tumors.
The Internet of Things (IoT) is an emerging technology that has gained a huge user base by facilitating Internet-connected devices being used in numerous applications including smart vehicular ...infrastructure. In this context, we focus on the traditional vehicular ad hoc network that has evolved into a new perception called the Internet of Vehicles (IoV), and is expected to soon transform into the Internet of Autonomous Vehicles (IoAV). IoAV hopes to facilitate smart vehicular infrastructure and autonomous driving without the need for human involvement. However, as the number of connected vehicles keeps increasing, so does the need for autonomous decision making. Hence, the IoAV must provide robust, secure, seamless, and scalable communication among the vehicles as well as the roadside units. This article provides an overview of autonomous vehicle communication layers, its associated properties, and security threats. Further, this article also briefly discusses the current research trends and future research issues.
Collaboration patterns offer important insights into how scientific breakthroughs and innovations emerge in small and large research groups. However, links in traditional networks account only for ...pairwise interactions, thus making the framework best suited for the description of two-person collaborations, but not for collaborations in larger groups. We therefore study higher-order scientific collaboration networks where a single link can connect more than two individuals, which is a natural description of collaborations entailing three or more people. We also consider different layers of these networks depending on the total number of collaborators, from one upwards. By doing so, we obtain novel microscopic insights into the representativeness of researchers within different teams and their links with others. In particular, we can follow the maturation process of the main topological features of collaboration networks, as we consider the sequence of graphs obtained by progressively merging collaborations from smaller to bigger sizes starting from the single-author ones. We also perform the same analysis by using publications instead of researchers as network nodes, obtaining qualitatively the same insights and thus confirming their robustness. We use data from the arXiv to obtain results specific to the fields of physics, mathematics, and computer science, as well as to the entire coverage of research fields in the database.
Earlier I hypothesized that hereditary tumors might participate in the evolution of multicellular organisms. I formulated the hypothesis of evolution by tumor neofunctionalization, which suggested ...that the evolutionary role of hereditary tumors might consist in supplying evolving multicellular organisms with extra cell masses for the expression of evolutionarily novel genes and the origin of new cell types, tissues, and organs. A new theory-the carcino-evo-devo theory-has been developed based on this hypothesis.
My lab has confirmed several non-trivial predictions of this theory. Another non-trivial prediction is that evolutionarily new organs if they originated from hereditary tumors or tumor-like structures, should recapitulate some tumor features in their development. This paper reviews the tumor-like features of evolutionarily novel organs. It turns out that evolutionarily new organs such as the eutherian placenta, mammary gland, prostate, the infantile human brain, and hoods of goldfishes indeed have many features of tumors. I suggested calling normal organs, which have many tumor features, the tumor-like organs.
Tumor-like organs might originate from hereditary atypical tumor organs and represent the part of carcino-evo-devo relationships, i.e., coevolution of normal and neoplastic development. During subsequent evolution, tumor-like organs may lose the features of tumors and the high incidence of cancer and become normal organs without (or with almost no) tumor features.
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