Since the first successful application of messenger ribonucleic acid (mRNA) as a vaccine agent in a preclinical study nearly 30 years ago, numerous advances have been made in the field of mRNA ...therapeutic technologies. This research uncovered the unique favorable characteristics of mRNA vaccines, including their ability to give rise to non-toxic, potent immune responses and the potential to design and upscale them rapidly, making them excellent vaccine candidates during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the first two vaccines against COVID-19 to receive accelerated regulatory authorization were nucleoside-modified mRNA vaccines, which showed more than 90% protective efficacy against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alongside tolerable safety profiles in the pivotal phase III clinical trials. Real-world evidence following the deployment of global vaccination campaigns utilizing mRNA vaccines has bolstered clinical trial evidence and further illustrated that this technology can be used safely and effectively to combat COVID-19. This unprecedented success also emphasized the broader potential of this new drug class, not only for other infectious diseases, but also for other indications, such as cancer and inherited diseases. This review presents a brief history and the current status of development of four mRNA vaccine platforms, nucleoside-modified and unmodified mRNA, circular RNA, and self-amplifying RNA, as well as an overview of the recent progress and status of COVID-19 mRNA vaccines. We also discuss the current and anticipated challenges of these technologies, which may be important for future research endeavors and clinical applications.
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The COVID-19 pandemic has highlighted the powerful clinical potential of mRNA vaccines. The authors give an overview of the recent status of COVID-19 vaccine candidates on the different mRNA platforms, including the approved nucleoside-modified mRNA vaccines, and briefly discuss the challenges and the future of this technology.
In a recent paper, Cabbolet argues that the PBR theorem is nonreal since in the ensemble interpretation of quantum mechanics the entangled measurement used in the derivation of the PBR theorem is ...nonexisting. However, Cabbolet (1) does not provide any argument for the nonexistence of entangled measurements beyond the incompatibility of the existence of entangled measurements and the existence of
ψ
-epistemic models which we already know from the PBR theorem; and (2) he does not show why it is more reasonable to abandon entangled measurements instead of
ψ
-epistemic models. Hence, the PBR theorem remains intact.
This paper presents the results of energy analysis of absorption heat pumps. The thermo-chemical instability term was introduced for absorption heat pumps used for heating or cooling or heating and ...cooling. A higher thermo-chemical instability results in the equipment being more sensitive with regard to the variation of the heat source flux. This sensitivity can be taken into account when heat sources are chosen for a certain absorption machine. Absorption heat pumps having thermo-chemical compressors were compared from energy demand and energy efficiency points of view with heat pumps having mechanical compressors. As it is shown, for certain evaporation and condensation temperature values, an absorption heat pump with similar efficiency to that of the heat pump with a mechanical compressor can always be found.
Radiant cooling systems (wall and ceiling) are low exergy systems which can help in solving efficiently the comfort needs of occupants. However, a complex energy and exergy analysis should be done in ...the design phase of such cooling systems in order to choose the most appropriate solution. This paper attempts to present a mathematical model and methodology of such a complex analysis and illustrates through a case study the energy and exergy comparison of cooling systems with mechanical compression and absorption cooling systems. Simple relations were developed in order to evaluate rapidly the energy and exergy efficiency of these types of cooling systems taking into account the avoidance of surface condensation. It was proven that, besides the coefficient of performances of installed chillers, the temperatures in the generator and absorber, respectively the supply and return temperatures are the main influencing factors of the exergy efficiencies of such types cooling systems. Based on the developed mathematical method a numerical analysis was done assuming different operational parameters of the cooling system used in practice.
•The maximal heat load, neutralizable with radiant cooling, was determined.•The relations for exergy content calculation of the “cold energy” were presented.•Three new evaluation indices were introduced for radiant cooling systems.•The energy and exergy efficiencies of the whole cooling systems were analysed.
It will be shown that the Peres–Mermin square admits value-definite noncontextual hidden-variable models if the observables associated with the operators can be measured only sequentially but not ...simultaneously. Namely, sequential measurements allow for noncontextual models in which hidden states update between consecutive measurements. Two recent experiments realizing the Peres–Mermin square by sequential measurements will also be analyzed along with other hidden-variable models accounting for these experiments.
The share of cooling is rising in the energy balance of buildings. The reason is for increasing occupants’ comfort needs, which is accentuated by the fact that the number and the amplitude of heat ...waves are increasing. The comfortable and healthy indoor environment should to be realized with the minimum amount of energy and fossil fuels. In order to meet this goal, designers should know the effect of different parameters on the buildings’ energy consumption. The energy need for cooling is mainly influenced by the glazed ratio and orientation of the facades, the quality of glazing and shading. In this paper the heat load analysis was done by assuming different types of summer days and surface cooling, depending on the glazing ratio, shading factor and solar factor of glazing. It was proven that, for a certain parameter, the sensitivity of the heat load depends on the orientation and chosen summer day. If the glazing area is doubled, the heat load increases with about 30%. Decreasing the glazed area to 50%, the heat load decreases with about 10%. The heat load decreases with about 3% if the g factor is lowered with 25% or the shading factor is reduced with 60%.
A more accurate determination of energy demands for buildings is of utmost importance for estimating future energy demands. This article presents two novel ideas that have the potential to contribute ...to a more precise determination of expected energy demands. The first idea involves accounting for a building’s function more thoroughly, which enables the determination of different energy demands for two or more identical buildings, depending on their respective usage functions. According to a case study, the heating energy demand can be up to twice as high in a commercial facility compared with a residential building. Similarly, the cooling energy requirement can also differ. The second idea concerns determining the heating degree day (HDD) and cooling degree day (CDD) values from the daily minimum and maximum temperatures. This idea may be relevant when few instantaneous values are available for the daily mean temperature. According to the case study, the calculated values from the daily minimum and maximum temperatures follow the HDD and CDD values specified from the daily mean temperature. However, the difference is less than 2% for the heating season and higher for the cooling season. Therefore, further research is required to refine the constants in the cooling equation.
Microglia are the main immune cells in the brain and have roles in brain homeostasis and neurological diseases. Mechanisms underlying microglia-neuron communication remain elusive. Here, we ...identified an interaction site between neuronal cell bodies and microglial processes in mouse and human brain. Somatic microglia-neuron junctions have a specialized nanoarchitecture optimized for purinergic signaling. Activity of neuronal mitochondria was linked with microglial junction formation, which was induced rapidly in response to neuronal activation and blocked by inhibition of P2Y12 receptors. Brain injury-induced changes at somatic junctions triggered P2Y12 receptor-dependent microglial neuroprotection, regulating neuronal calcium load and functional connectivity. Thus, microglial processes at these junctions could potentially monitor and protect neuronal functions.
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