Classical Strategies Research Articles

Chromosome Transplantation: Opportunities and Limitations.

There are thousands of rare genetic diseases that could be treated with classical gene therapy strategies such as the addition of the defective gene via viral or non-viral delivery or by direct gene editing. However, several genetic defects are too complex for these approaches. These "genomic mutations" include aneuploidies, intra and inter chromosomal rearrangements, large deletions, or inversion and copy number variations. Chromosome transplantation (CT) refers to the precise substitution of an endogenous chromosome with an exogenous one. By the addition of an exogenous chromosome and the concomitant elimination of the endogenous one, every genetic defect, irrespective of its nature, could be resolved. In the current review, we analyze the state of the art of this technique and discuss its possible application to human pathology. CT might not be limited to the treatment of human diseases. By working on sex chromosomes, we showed that female cells can be obtained from male cells, since chromosome-transplanted cells can lose either sex chromosome, giving rise to 46,XY or 46,XX diploid cells, a modification that could be exploited to obtain female gametes from male cells. Moreover, CT could be used in veterinary biology, since entire chromosomes containing an advantageous locus could be transferred to animals of zootechnical interest without altering their specific genetic background and the need for long and complex interbreeding. CT could also be useful to rescue extinct species if only male cells were available. Finally, the generation of "synthetic" cells could be achieved by repeated CT into a recipient cell. CT is an additional tool for genetic modification of mammalian cells.

DKK3 Expression in Glioblastoma: Correlations with Biomolecular Markers.

Glioblastoma is the most common malignant primary tumor of the CNS. The prognosis is dismal, with a median survival of 15 months. Surgical treatment followed by adjuvant therapies such as radiotherapy and chemotherapy characterize the classical strategy. The WNT pathway plays a key role in cellular proliferation, differentiation, and invasion. The DKK3 protein, capable of acting as a tumor suppressor, also appears to be able to modulate the WNT pathway. We performed, in a series of 40 patients, immunohistochemical and Western blot evaluations of DKK3 to better understand how the expression of this protein can influence clinical behavior. We used a statistical analysis, with correlations between the expression of DKK3 and overall survival, age, sex, Ki-67, p53, and MGMT and IDH status. We also correlated our data with information included in the cBioPortal database. In our analyses, DKK3 expression, in both immunohistochemistry and Western blot analyses, was reduced or absent in many cases, showing downregulation. To date, no clinical study exists in the literature that reports a potential correlation between IDH and MGMT status and the WNT pathway through the expression of DKK3. Modulation of this pathway through the expression of DKK3 could represent a new tailored therapeutic strategy in the treatment of glioblastoma.

New strategy for anti-loop formulations

This paper presents a strategy based on binary labelling of nodes for the creation of anti-loop formulations from existing strategies. This strategy prevents by default the formation of odd cycles, therefore it can have important role in iterative procedures based on generating subtour elimination constraints. It can also be used to modify the classic strategies used in problems associated to graphs. In this paper we focus on this last application. The behavior of this strategy is analyzed with two problems associated with graphs, the Asymmetric Traveling Salesman Problem (ATSP) and the Steiner Problem, where two configurations that modify the Miller-Tucking-Zemlig proposal to avoid cycles are compared. The experimental analysis shows that this strategy keep a good convergence, highlighting its use for the Steiner problem.

Cephalopod-Inspired Chemical-Gated Hydrogel Actuation Systems for Information 3D-Encoding Display.

Cephalopods evolve the acetylcholine-gated actuation control function of their skin muscles, which enables their dynamic/static multimode display capacities for achieving perfectly spatial control over the colors/patterns on every inch of skin. Reproduction of artificial analogs that exhibit similar multimodal display is essential to reach advanced information three-dimensional (3D) encoding with higher security than the classic 2D-encoding strategy, but remains underdeveloped. The core difficulty is how to replicate such chemical-gated actuation control function into artificial soft actuating systems. Herein, this work proposes to develop azobenzene-functionalized poly(acrylamide) (PAAm) hydrogel systems, whose upper critical solution temperature (UCST) type actuation responsiveness can be intelligently programmed or even gated by the addition of hydrophilic α-cyclodextrin (α-CD) molecules for reversible association with pendant azobenzene moieties via supramolecular host-guest interactions. By employing such α-CD-gated hydrogel actuator as an analogue of cephalopods' skin muscle, biomimetic mechanically modulated multicolor fluorescent display systems are designed, which demonstrate a conceptually new α-CD-gated "thermal stimulation-hydrogel actuation-fluorescence output" display mechanism. Consequently, high-security 3D-encoding information carriers with an unprecedented combination of single-input multiple-output, dynamic/static dual-mode and spatially controlled display capacities are achieved. This bioinspired strategy brings functional-integrated features for artificial display systems and opens previously unidentified avenues for information security.

Novel item selection strategies for cognitive diagnostic computerized adaptive testing: A heuristic search framework.

The computerized adaptive form of cognitive diagnostic testing, CD-CAT, has gained increasing attention in the domain of personalized measurements for its ability to categorize individual mastery status of fine-grained attributes more accurately and efficiently through administering items tailored to one's ability progressively. How to select the next item based on previous response(s) is crucial for the success of CD-CAT. Previous item selection strategies for CD-CAT have often followed a greedy or semi-greedy approach, which makes it difficult to strike a balance between diagnostic performance and item bank utilization. To address this issue, this study takes a graph perspective and transforms the item selection problem in CD-CAT into a path-searching problem, in which paths refer to possible test construction and nodes refer to individual items. A heuristic function is defined to predict the prospect of a path, indicating how well the corresponding test can diagnose the current examinee. Two search mechanisms with different biases towards item exposure control are proposed to approximate the optimal path with the best prospect. The first unused item on the resulting path is selected as the next item. The above components compose a novel CD-CAT item selection framework based on heuristic search. Simulation studies are conducted under a variety of conditions regarding bank designs, bank-quality conditions, and testing scenarios. The results are compared with different types of classic item selection strategies in CD-CAT, showing that the proposed framework can enhance bank utilization at a smaller cost of diagnostic performance.

Adaptive Space-Aware Infotaxis II as a Strategy for Odor Source Localization.

Mobile robot olfaction of toxic and hazardous odor sources is of great significance in anti-terrorism, disaster prevention, and control scenarios. Aiming at the problems of low search efficiency and easily falling into a local optimum of the current odor source localization strategies, the paper proposes the adaptive space-aware Infotaxis II algorithm. To improve the tracking efficiency of robots, a new reward function is designed by considering the space information and emphasizing the exploration behavior of robots. Considering the enhancement in exploratory behavior, an adaptive navigation-updated mechanism is proposed to adjust the movement range of robots in real time through information entropy to avoid an excessive exploration behavior during the search process, which may lead the robot to fall into a local optimum. Subsequently, an improved adaptive cosine salp swarm algorithm is applied to confirm the optimal information adaptive parameter. Comparative simulation experiments between ASAInfotaxis II and the classical search strategies are carried out in 2D and 3D scenarios regarding the search efficiency and search behavior, which show that ASAInfotaxis II is competent to improve the search efficiency to a larger extent and achieves a better balance between exploration and exploitation behaviors.

Lithium Metal Anode in Electrochemical Perspective

AbstractLithium metal is a possible anode material for building high energy density secondary batteries, but its problems during cycling have hindered the commercialization of lithium metal secondary batteries. Until now, many sophisticated techniques have been used to obtain rich micro‐morphological and physicochemical information of the deposition layer and the solid electrolyte interface (SEI), and to develop improvement strategies based on the information and achieve remarkable results. Regulating the reaction process around key links is a classic strategy to achieve expected results. Based on this empirical fact, we artificially highlighted the differences in the apparent performance of lithium metal anode using different series of electrolytes. We used microelectrode technology to analyze the reaction mechanisms and kinetic characteristics of each elementary step under all electrolyte conditions, revealing common laws that affect apparent performance and the basic steps that have a decisive impact on apparent performance. We discussed and elucidated the relevant physical and chemical principles, providing a clear basis for improving the pertinence and efficiency of improvement strategies.

LISR: Learning Linear 3D Implicit Surface Representation Using Compactly Supported Radial Basis Functions

Implicit 3D surface reconstruction of an object from its partial and noisy 3D point cloud scan is the classical geometry processing and 3D computer vision problem. In the literature, various 3D shape representations have been developed, differing in memory efficiency and shape retrieval effectiveness, such as volumetric, parametric, and implicit surfaces. Radial basis functions provide memory-efficient parameterization of the implicit surface. However, we show that training a neural network using the mean squared error between the ground-truth implicit surface and the linear basis-based implicit surfaces does not converge to the global solution. In this work, we propose locally supported compact radial basis functions for a linear representation of the implicit surface. This representation enables us to generate 3D shapes with arbitrary topologies at any resolution due to their continuous nature. We then propose a neural network architecture for learning the linear implicit shape representation of the 3D surface of an object. We learn linear implicit shapes within a supervised learning framework using ground truth Signed-Distance Field (SDF) data for guidance. The classical strategies face difficulties in finding linear implicit shapes from a given 3D point cloud due to numerical issues (requires solving inverse of a large matrix) in basis and query point selection. The proposed approach achieves better Chamfer distance and comparable F-score than the state-of-the-art approach on the benchmark dataset. We also show the effectiveness of the proposed approach by using it for the 3D shape completion task.

Trajectory Tracking and Disturbance Rejection Performance Analysis of Classical and Advanced Controllers for a SCORBOT Robot

This work presents the design and assessment of four control schemes for the monitoring and regulation of joint trajectories applied in the dynamic model of a SCORBOT-ER V plus robot, which includes the dynamics of the actuators, and the estimation of the friction forces present within the joints. The two classical control strategies calculated torque and PID, and the two advanced control strategies, fuzzy and predictive, are considered. In the latter case, a gravitational compensation stage is incorporated, as well as the inverse models of the motors and the transmissions of belt movement for each joint. Computational tests are performed by applying an external step-type disturbance to the third joint of the robot. Finally, an evaluation of the results obtained is presented through trajectory curves, joint errors, and the three performance indexes residual mean square, residual standard deviation, and index of agreement.

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer.

Experimental and computational studies illuminating the factors that guide metal-centered stereogenicity and, therefrom, selectivity in transfer hydrogenative carbonyl additions of alcohol proelectrophiles catalyzed by chiral-at-metal-and-ligand octahedral d6 metal ions, iridium(III) and ruthenium(II), are described. To augment or invert regio-, diastereo-, and enantioselectivity, predominantly one from among as many as 15 diastereomeric-at-metal complexes is required. For iridium(III) catalysts, cyclometalation assists in defining the metal stereocenter, and for ruthenium(II) catalysts, iodide counterions play a key role. Whereas classical strategies to promote selectivity in metal catalysis aim for high-symmetry transition states, well-defined low-symmetry transition states can unlock selectivities that are otherwise difficult to achieve or inaccessible.

Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery

The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment of viral particles to the host cell membrane receptor and membrane fusion. Due to its crucial involvement in the initial phases of influenza A infections, HA emerges as a promising target in the search of novel drug-like candidates. Given its pivotal role in the early stages of influenza A infections, intense drug discovery efforts have been undertaken to target HA in the past decades. Drug discovery studies mainly rely on preventing the recognition of sialic acid units by the receptor binding site in the globular head (GH) domain, or the conformational rearrangement required for the fusion of viral and cell membranes. In this work, the aim is to summarize the progress made in HA-targeted development of small molecule fusion inhibitors. To this end, attention will primarily be focused on the analysis of the X-ray crystallographic structures of HA bound to fusion inhibitors. Furthermore, this study also aims to highlight the efforts made in exploiting the structural information in conjunction with molecular modeling techniques to discern the mechanism of action of the fusion inhibitors and to assist the design and interpretation of structure-activity relationships of novel lead compounds will be highlighted. The final section will be dedicated to elucidating novel and promising antiviral strategies proceeding from the transformation of known small molecule antivirals in proteolysis targeting chimera (PROTAC)-based targeted protein degradation. This knowledge will be valuable to assist the exploitation of classical and novel antiviral structure-based strategies, together with a deeper understanding of the mechanism of action and minimization of the impact of drug resistance.

Product digitization and differentiation strategy change: Evidence from the book publishing industry

AbstractResearch SummaryWe study product digitization as an impetus for firm strategy change. Product digitization can erode a firm's ability to differentiate through physical product attributes and prompts them to increase emphasis on nonphysical product attributes to sustain their competitive advantage. We expect this effect is pronounced among firms that have pursued a physical differentiation strategy prior to the digital age. However, we expect that countervailing forces exist such that the internal supply cost of and the external market demand for the nonphysical differentiator mitigate this effect. Evidence from publishers in the Amazon Kindle e‐book ecosystem supports our hypotheses. This study bridges the growing digital strategy literature and the classical competitive strategy literature. We discuss how our findings are relevant to a range of industries.Managerial SummaryMany companies invest in superior physical product attributes to increase a customer's willingness‐to‐pay and entice purchase. However, when products become digitized—such as music streaming displacing CDs or e‐books replacing printed books—the effectiveness of physical product differentiation is diminished. We examine how book publishers manage this challenge at the advent of Amazon's Kindle e‐book technology. We find that publishers that have emphasized physical product attributes turn to emphasizing nonphysical product differentiation, namely, through offering more content. Yet, the extent of the strategy change is limited by the internal development cost of and the external demand for the nonphysical differentiator. We discuss how our findings are relevant to a range of settings, including both product and service companies.

The Relationship Between the Strategy of Russian Companies and Their Policies in the Field of Human Capital

In modern conditions of instability of the national economic system, the question of effective strategic planning and implementation of an organizational strategy covering all levels of the corporation becomes relevant. The post-pandemic period and the shock year 2022 for many Russian companies forced the top management of many corporations to respon3d flexibly to the current realities of the global market, changing previous strategies. Interesting in this regard are the factors that shape the organizational strategies of the corporations under study. The author presents an attempt to analyze the effectiveness of Russian companies from the chosen type of strategy in relation to the policy in the field of use of human capital. In particular, economically important companies using classical planned and classical process strategies are considered. Based on the study, it was revealed that there is a relationship between organizational strategy and management policy in the field of human capital; moreover, the higher it is, the more successful companies are (expressed in caring for employees). Also, as a distinctive factor shaping organizational strategies, the author identified the policy in the field of labor protection and industrial safety (which is a feature of companies with a classic process strategy).

Contexts for integrating classical music in vulnerable educational environments

Intersectional intervention on educational policies in 21st century society is noted as a viable alternative in disadvantaged educational settings. In this direction, a well-reasoned educational policy facilitates access to education and knowledge for a significant number of students. The vision of each teacher, and in general of an educator, must be aimed at comprehensive educational policies, consistent with educational ideals and the agreed school curriculum, the skills of each educator being evident in the way they can adapt and apply classical or modern educational strategies or concepts, capable of producing much needed change in the evolution and school performance of the beneficiaries of this social service. The involvement of music education in the formation of the modern pupil's personality can be the foundation on which to build an equitable and inclusive education system, providing pupils with valuable opportunities to develop cognitive, social and emotional skills.

Water resources management in the context of the circular economy concept

The article examines the essence and main goals of the circular economy. The connection between the circular economy and the achievement of the goals of sustainable development has been studied. The positive effect of the introduction of the circular economy for the social, economic and ecological system was determined. Reducing the scarcity of natural resources, as well as the creation of durable goods, allows reducing the negative impact on the environment, which in turn stimulates innovation, which increases competitive advantages in international markets. The peculiarities of the development of circular economy models in developed countries are considered. The peculiarities of the economic category of water and its role in the economy are analyzed. The different roles of water emphasize its uniqueness and prove the difficulty of adopting a unified approach to it in the circular economy. The dynamics of indicators of the water capacity of Ukraine's GDP and volumes of return (waste) water discharged into surface water bodies were analyzed. It was determined that the rethinking of the urban water supply system through the principles of the circular economy and the goals of sustainable development will reduce the amount of polluted water and increase its reuse. It was determined that Ukraine is one of the least water-supplied countries in Europe, the annual runoff reserves available for use per person do not exceed 1,000 m3, while the GDP water capacity indicator remains sufficiently high and exceeds its target value. The dynamics of the indicator of the water capacity of the GDP of Ukraine has been analyzed, it has a tendency to decrease for the years 2015-2022. The characteristic problems of the functioning of urban water supply and drainage systems in the front-line territories and safer cities, where the number of internally displaced people has increased, are analyzed. It was analyzed that not all classic circular economy strategies can be applied to water. Strategies of the circular economy of water are considered and it is emphasized that rethinking is inherent in all water strategies. It has been analyzed that the implementation of the circular economy may face financial, bureaucratic and behavioral problems and regulatory, legislative, managerial and implementation obstacles. Keywords: circular economy, water resources, sustainable development, integrated management of water resources, state policy, goals of sustainable development, strategies, economic model, water supply and drainage system

Quantifying the performance enhancement facilitated by fractional-order implementation of classical control strategies for nanopositioning

For most nanopositioning systems, maximizing positioning bandwidth to accurately track periodic and aperiodic reference signals is the primary performance goal. Closed-loop control schemes are employed to overcome the inherent performance limitations such as mechanical resonance, hysteresis and creep. Most reported control schemes are integer-order and combine both damping and tracking actions. In this work, fractional-order controllers from the positive position feedback family namely: the Fractional-Order Integral Resonant Control (FOIRC), the Fractional-Order Positive Position Feedback (FOPPF) controller, the Fractional-Order Positive Velocity and Position Feedback (FOPVPF) controller and the Fractional-Order Positive, Acceleration, Velocity and Position Feedback (FOPAVPF) controller are designed and analysed. Compared with their classical integer-order implementation, the fractional-order damping and tracking controllers furnish additional design (tuning) parameters, facilitating superior closed-loop bandwidth and tracking accuracy. Detailed simulated experiments are performed on recorded frequency-response data to validate the efficacy, stability and robustness of the proposed control schemes. The results show that the fractional-order versions deliver the best overall performance.

A multiplexed, confinable CRISPR/Cas9 gene drive can propagate in caged Aedes aegypti populations

Aedes aegypti is the main vector of several major pathogens including dengue, Zika and chikungunya viruses. Classical mosquito control strategies utilizing insecticides are threatened by rising resistance. This has stimulated interest in new genetic systems such as gene drivesHere, we test the regulatory sequences from the Ae. aegypti benign gonial cell neoplasm (bgcn) homolog to express Cas9 and a separate multiplexing sgRNA-expressing cassette inserted into the Ae. aegypti kynurenine 3-monooxygenase (kmo) gene. When combined, these two elements provide highly effective germline cutting at the kmo locus and act as a gene drive. Our target genetic element drives through a cage trial population such that carrier frequency of the element increases from 50% to up to 89% of the population despite significant fitness costs to kmo insertions. Deep sequencing suggests that the multiplexing design could mitigate resistance allele formation in our gene drive system.

Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists.

Metal-Based Nanoparticles for Cardiovascular Diseases.

Globally, cardiovascular diseases (CVDs) are the leading cause of death and disability. While there are many therapeutic alternatives available for the management of CVDs, the majority of classic therapeutic strategies were found to be ineffective at stopping or significantly/additionally slowing the progression of these diseases, or they had unfavorable side effects. Numerous metal-based nanoparticles (NPs) have been created to overcome these limitations, demonstrating encouraging possibilities in the treatment of CVDs due to advancements in nanotechnology. Metallic nanomaterials, including gold, silver, and iron, come in various shapes, sizes, and geometries. Metallic NPs are generally smaller and have more specialized physical, chemical, and biological properties. Metal-based NPs may come in various forms, such as nanoshells, nanorods, and nanospheres, and they have been studied the most. Massive potential applications for these metal nanomaterial structures include supporting molecular imaging, serving as drug delivery systems, enhancing radiation-based anticancer therapy, supplying photothermal transforming effects for thermal therapy, and being compounds with bactericidal, fungicidal, and antiviral qualities that may be helpful for cardiovascular diseases. In this context, the present paper aims to review the applications of relevant metal and metal oxide nanoparticles in CVDs, creating an up-to-date framework that aids researchers in developing more efficient treatment strategies.

A Quantum Double-or-Nothing Game: An Application of the Kelly Criterion to Spins.

A quantum game is constructed from a sequence of independent and identically polarised spin-1/2 particles. Information about their possible polarisation is provided to a bettor, who can wager in successive double-or-nothing games on measurement outcomes. The choice at each stage is how much to bet and in which direction to measure the individual particles. The portfolio's growth rate rises as the measurements are progressively adjusted in response to the accumulated information. Wealth is amassed through astute betting. The optimal classical strategy is called the Kelly criterion and plays a fundamental role in portfolio theory and consequently quantitative finance. The optimal quantum strategy is determined numerically and shown to differ from the classical strategy. This paper contributes to the development of quantum finance, as aspects of portfolio optimisation are extended to the quantum realm. Intriguing trade-offs between information gain and portfolio growth are described.