In this work, we introduce a new workflow to solve portfolio optimization problems on annealing platforms. We combine a classical preprocessing step with a modified unconstrained binary optimization ...(QUBO) model and evaluate it using simulated annealing (classical computer), digital annealing (Fujitsu’s Digital Annealing Unit), and quantum annealing (D-Wave Advantage). Starting from Markowitz’s theory on portfolio optimization, our classical preprocessing step finds the most promising assets within a set of possible assets to choose from. We then modify existing QUBO models for portfolio optimization, such that there are no limitations on the number of assets that can be invested in. Furthermore, our QUBO model enables an investor to also place an arbitrary amount of money into each asset. We apply this modified QUBO to the set of promising asset candidates we generated previously via classical preprocessing. A solution to our QUBO model contains information about what percentage of the whole available capital should be invested into which asset. For the evaluation, we have used publicly available real-world data sets of stocks of the New York Stock Exchange as well as common ETFs. Finally, we have compared the respective annealing results with randomly generated portfolios by using the return, variance, and diversification of the created portfolios as measures. The results show that our QUBO formulation is capable of creating well-diversified portfolios that respect certain criteria given by an investor, such as maximizing return, minimizing risk, or sticking to a certain budget.
This study aims to present the problems associated with the use of information from private internal investigation in a criminal process. The paper first presents the essence, functions, limits, and ...purposes of internal investigations, taking into account legal restrictions, including constitutional ones. Further in the paper, the authors critically analyze the possibility of using materials obtained and produced in internal investigations in criminal proceedings. A significant number of internal investigations are conducted by attorneys. Therefore, the paper also evaluates the permissibility of abolishing the attorney-client privilege and of the court or the law enforcement agencies obtaining the materials produced by an attorney in the course of an internal investigation or questioning of the lawyer. Having an attorney conduct an internal investigation improves the security of the information produced in the course of the internal investigation, as the materials are covered by the attorney-client privilege. However, one should bear in mind that in Poland this is not an absolute protection. The considerations led the authors to the conclusion that internal investigations are a valuable tool of the system for preventing irregularities in corporations and an important source of materials that can be used in criminal proceedings.
Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. ...Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.
The effect of bulk alkali (Li, Na, K, Cs) promotion on the tungsten(VI) oxide catalytic activity in soot oxidation was investigated. Catalyst oxidation and reduction susceptibility investigations ...have shown, that soot oxidation on the investigated catalysts operates through Mars van Krevelen mechanism. It has been also revealed, that increase in electrodonor properties (lowering the work function) of the AxWO3 (ALi, Na, K, Cs) catalysts results in enhancing the catalytic activity in soot oxidation with the promotional effect increasing in order: Cs<Na≪K≈Li.
•Soot oxidation on alkali tungsten bronzes involves lattice oxygen.•Oxygen mobility increases as: WO3<Cs0.3WO3<Na0.3WO3<K0.3WO3≈Li0.3WO3.•Correlation between catalyst work function and soot oxidation activity is established.
Catalytic combustion of hazardous particulate matter (soot) generated by automobile engines is a primary method of their elimination. Ruthenium-based catalysts are a promising alternative for ...traditional noble metal (Pt, Pd) based systems; however, their relatively poor thermal stability hinders wide applications. In this study, we synthesized a novel, highly active, and stable catalyst for soot oxidation containing bimetallic RuRe nanoparticles supported on TiO
2
. The RuRe NPs were synthesized by colloidal, microwave-assisted polyol method and deposited on rutile or anatase TiO
2
. The effect of rhenium content and the nature of TiO
2
support on the performance of RuRe nanoparticles (NPs) in the soot oxidation under air atmosphere was investigated. Bimetallic RuRe/TiO
2
nanocatalysts exhibited higher activity in the soot oxidation than Ru/TiO
2
systems, and the rutile supported 2 wt% Ru–0.4 wt% Re nanocatalyst (Ru/Re atomic ratio of 9:1) showed the best catalytic performance (T
50
= 340 °C and T
90
< 400 °C). All studied nanocatalysts were stable under reaction conditions in the consecutive catalytic tests. The exceptional catalytic performance of bimetallic RuRe NPs is explained by the synergy effect between ruthenium, rhenium, and TiO
2
.
Graphical Abstract
The oxidation of soot over RuRe bimetallic nanoparticles (NPs) supported on γ-Al
2
O
3
has been investigated. The catalysts were synthesized by a microwave-polyol method and characterized by ICP, ...BET, TEM, STEM-EDS, XRD and XPS techniques. The study revealed that the proper choice of the Re loading (0.4–2.0 wt%) is crucial for the catalytic behavior of the 2% Ru–Re/Al
2
O
3
nano-catalysts.The best catalytic properties, in terms of overall activity and stability, were observed for the 2%Ru-0.8%Re/γ-Al
2
O
3
nano-catalyst. The stability of all bimetallic 2% Ru–Re nano-catalysts in catalytic soot oxidation in the presence of oxygen is very high in contrast to the 2% Ru/γ-Al
2
O
3
sample. The presence of rhenium in the catalytic system hinder the formation of large RuO
2
agglomerates leading to a better dispersion of active ruthenium phase and a better catalytic performance. The relationship between the catalytic activity of Ru–Re/γ-Al
2
O
3
and the synergetic roles of Ru and Re is discussed.
Lipid Nanoparticles (LNPs) are promising drug delivery systems for various RNAs such as small interfering (siRNA) and messenger RNA (mRNA). Microfluidic mixing is a common technique to encapsulate ...RNA in LNPs. However, high flow rates and lipid concentrations are used for LNP formation to control LNP size as well as RNA encapsulation efficiency. We investigated the feasibility of downscaling siRNA and mRNA LNP manufacturing to save materials and enable a broader access to this technology. To optimize such a down-scaled procedure, we evaluated physicochemical nanoparticle characteristics including hydrodynamic diameter, zeta potential, particle concentration, encapsulation efficiency, and recovery for LNPs produced with three different microfluidic methods. We observed differences in nanoparticle characteristics and in vitro performance regarding cellular uptake, gene silencing, and mRNA expression. We determined the gene knockdown ability of the best siRNA LNPs formulation ex vivo using precision-cut lung slices to highlight the translational character of LNPs for inhalation and observed comparable efficacy as with a commercially available transfection reagent.
Catalytic combustion of hazardous particulate matter (soot) generated by automobile engines is a primary method of their elimination. Ruthenium-based catalysts are a promising alternative for ...traditional noble metal (Pt, Pd) based systems; however, their relatively poor thermal stability hinders wide applications. In this study, we synthesized a novel, highly active, and stable catalyst for soot oxidation containing bimetallic RuRe nanoparticles supported on TiO.sub.2. The RuRe NPs were synthesized by colloidal, microwave-assisted polyol method and deposited on rutile or anatase TiO.sub.2. The effect of rhenium content and the nature of TiO.sub.2 support on the performance of RuRe nanoparticles (NPs) in the soot oxidation under air atmosphere was investigated. Bimetallic RuRe/TiO.sub.2 nanocatalysts exhibited higher activity in the soot oxidation than Ru/TiO.sub.2 systems, and the rutile supported 2 wt% Ru-0.4 wt% Re nanocatalyst (Ru/Re atomic ratio of 9:1) showed the best catalytic performance (T.sub.50 = 340 °C and T.sub.90 < 400 °C). All studied nanocatalysts were stable under reaction conditions in the consecutive catalytic tests. The exceptional catalytic performance of bimetallic RuRe NPs is explained by the synergy effect between ruthenium, rhenium, and TiO.sub.2.
Abstract
RNA-protein interactions determine the cellular fate of RNA and are central to regulating gene expression outcomes in health and disease. To date, no method exists that is able to identify ...proteins that interact with specific regions within endogenous RNAs in live cells. Here, we develop SHIFTR (Selective RNase H-mediated interactome framing for target RNA regions), an efficient and scalable approach to identify proteins bound to selected regions within endogenous RNAs using mass spectrometry. Compared to state-of-the-art techniques, SHIFTR is superior in accuracy, captures minimal background interactions and requires orders of magnitude lower input material. We establish SHIFTR workflows for targeting RNA classes of different length and abundance, including short and long non-coding RNAs, as well as mRNAs and demonstrate that SHIFTR is compatible with sequentially mapping interactomes for multiple target RNAs in a single experiment. Using SHIFTR, we comprehensively identify interactions of cis-regulatory elements located at the 5′ and 3′-terminal regions of authentic SARS-CoV-2 RNAs in infected cells and accurately recover known and novel interactions linked to the function of these viral RNA elements. SHIFTR enables the systematic mapping of region-resolved RNA interactomes for any RNA in any cell type and has the potential to revolutionize our understanding of transcriptomes and their regulation.
Graphical Abstract
Graphical Abstract
Regulation of viral RNA biogenesis is fundamental to productive SARS-CoV-2 infection. To characterize host RNA-binding proteins (RBPs) involved in this process, we biochemically identified proteins ...bound to genomic and subgenomic SARS-CoV-2 RNAs. We find that the host protein SND1 binds the 5′ end of negative-sense viral RNA and is required for SARS-CoV-2 RNA synthesis. SND1-depleted cells form smaller replication organelles and display diminished virus growth kinetics. We discover that NSP9, a viral RBP and direct SND1 interaction partner, is covalently linked to the 5′ ends of positive- and negative-sense RNAs produced during infection. These linkages occur at replication-transcription initiation sites, consistent with NSP9 priming viral RNA synthesis. Mechanistically, SND1 remodels NSP9 occupancy and alters the covalent linkage of NSP9 to initiating nucleotides in viral RNA. Our findings implicate NSP9 in the initiation of SARS-CoV-2 RNA synthesis and unravel an unsuspected role of a cellular protein in orchestrating viral RNA production.
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•SND1 is required for nascent SARS-CoV-2 RNA synthesis early during infection•SND1 directly interacts with NSP9 and both proteins bind negative-sense viral RNA•NSP9 is covalently linked to viral RNA at initiation sites, indicating protein priming•SND1 modulates the covalent linkage of NSP9 to positive- and negative-sense viral RNA
Mapping of subgenome-resolved SARS-CoV-2 RNA-protein interactions reveals that the host protein SND1 binds negative-sense SARS-CoV-2 RNA and promotes viral RNA synthesis by recruiting NSP9, which likely serves as a protein primer for RNA production.
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