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This study aimed to evaluate the effect of different time of taking cutting and IBA concentrations on the rooting of Myrtus communis. White and black fruity myrtle types were used as plant materials. The cuttings were obtained from Batı Akdeniz Agricultural Research Institute (BATEM) collection garden. The effects of 0 (control), 500, 1000, 2000, 4000 and 8000 mg L-1 doses of IBA applications and time of taking cutting (February, March, April and May) on the rooting were investigated. The highest rooting percentage in black fruity myrtle was obtained from cuttings taken in February and applied 1000 mg L-1 (76.67%) IBA, while the lowest rooting was obtained from cuttings applied 500 mg L-1 taken in May. White fruity myrtle was rooted at a lower rate than black fruity myrtle. It was determined that the highest rooting percentage (43.33%), shooting percentage (43.33%), rooted-shooted rates (43.33%) and average root number (1.63 pcs) in the white fruity myrtle were 500 mg L-1 IBA dose in April. In addition, the study showed that the best rooting of white myrtle was in the cuttings taken in April and applied 500 mg L-1 IBA. As a result, it can be recommended to use the cuttings taken in April without any application for the best rooting in black fruity myrtle cuttings.

This letter presents an ultrasonically powered dual-wavelength optogenetic device that targets simultaneous excitation and inhibition of neural activities, or in a broader sense, optical stimulation in two distinct wavelengths for targeting different populations of neurons. This can be applied to a variety of neurological disorders. The device features a load regulator circuit that shares the available power budget between two LEDs in a power-efficient and controlled way suppressing the need for adaptive matching and overvoltage protection circuits. Furthermore, the regulator circuit is capable of detecting power burst availability on the device and generating a control signal, accordingly. For 5.25 -mW acoustic power at the device's surface, the rectified voltage, and the total current load of the system are regulated to 2.79 V and 600A , respectively. The maximum chip and device efficiencies of 92.5% and 31.8% are measured, respectively. The total die area in 180- nm CMOS technology nose and the estimated system volume are 0.16/2 and 0.572/3 , respectively.

The increasing threat of cyberattacks has resulted in increased efforts by both the U.K. government and regulatory authorities to coordinate efforts to influence cybersecurity risk management practices in the U.K. insurance sector, focusing on cyber risk underwriters. This paper provides an evaluation of these arrangements. It first provides a descriptive overview of the key U.K. regulatory authorities and the evolution of their efforts over the past decade, as well as the scope for broader collaborations with industry and member-based associations and international organisations. It then evaluates the effectiveness of these efforts by providing a multi-method study of the incidence, nature and evolution of cost of data breaches, investment in computer systems and software intangible assets at risk of cyberattack, and a content analysis of annual reports of both U.K. regulators and a sample of U.K. insurers. The findings suggest that while both the total costs of data breaches and the size of investment in computer systems and software intangibles at risk of cyberattack have gradually increased over time, the degree of engagement with cyber as a reporting issue by both cyber insurers and financial regulators has not. It is concluded that while these efforts have been apparently successful in avoiding a large-scale, systemic cyberattack on the U.K. insurance industry, there are significant gaps and overlaps in the system of cyber regulatory oversight.

A review of the control laws (models) of alternating current arc steelmaking furnaces’ (ASF) electric modes (EM) is carried out. A phase-symmetric three-component additive fuzzy model of electrode movement control signal formation is proposed. A synthesis of fuzzy inference systems based on the Sugeno model for the implementation of the proposed additive three-component fuzzy law of arc length control is performed. A structural computer Simulink model of the EM control system in a high-power arc steelmaking furnace of the DSP-200 type with an ARDM-T-12 arcs power regulator is created. Computer research into control dynamics indicators under the influence of deterministic perturbations and also integral indicators of energy efficiency when handling stationary random arc lengths fluctuations (corresponding to various technological stages of melting) are carried out. A comparative analysis of dynamics indicators, energy efficiency, and electromagnetic compatibility of the proposed fuzzy and known differential model of ASF arc lengths control is carried out. The implementation of the proposed fuzzy three-component additive control model in comparison with the existing deterministic differential one reduces the dispersion of voltages, currents, and arcs powers, reduces electrical losses in an arc furnace high-power network by 10–22% and increases the average arc power by 0.9–1.5%.

Plants have a dynamic immune system to protect themselves against pathogens. Recognition of a pathogen leads to the activation of this immune system, steered by different phytohormones. One of these, salicylic acid, regulates plant responses to biotrophic pathogens that thrive on living host tissue. Typical SA-mediated responses are the production of antimicrobial proteins and metabolites and the strengthening of the cell wall. These responses can occur both locally and systemically. Due to their nature, these responses cost energy and resources that cannot be invested in plant growth and development. This suppression also works the other way around: active growth and developmental processes suppress immunity. This mutual inhibition is called the growth-immunity tradeoff and is actively regulated by the plant. The research in this thesis is focused on the model plant Arabidopsis thaliana (thale cress), in which the SA content is controlled at the level of synthesis and catabolism. Two enzymes that catabolize SA through hydroxylation are the paralogous 2-oxoglutarate Fe(II)-dependent oxygenases DMR6/S5H (DOWNY MILDEW RESISTANT 6/SA 5-HYDROXYLASE) and DLO1/S3H (DMR6-LIKE OXYGENASE 1/SA 3-HYDROXYLASE). dmr6/dlo1 mutants have enhanced SA levels and therefore a constitutively active immune system and enhanced disease resistance. The high SA levels of double mutant plants cause hyperresistance but also dwarfism. On the other hand, overexpression of DMR6 or DLO1 leads to depletion of SA and thus enhanced susceptibility. We use the perturbed SA catabolism of the dmr6/dlo1 mutants and DMR6/DLO1 overexpression lines to investigate the SA-mediated growth-immunity tradeoff. We found that altered expression of DMR6 and/or DLO1 had major effects on the transcriptome that correlated to the plant’s SA content. We found that enhanced SA levels in dmr6/dlo1 mutants caused reduced photosynthetic efficiency and a sped up development and reduced SA levels in DMR6/DLO1 overexpression lines led to reduced pathogen-associated molecular pattern (PAMP)-triggered immune responses. We further identified a significant effect of the genetic background to perturbations in DMR6/DLO1 expression in different Arabidopsis accessions: several Arabidopsis accessions had a reduced growth tradeoff but retained high disease resistance. To systematically investigate the genetics behind regulation of the growth-immunity tradeoff, we further employed a forward genetics screen for restored growth and high resistance in dmr6-3 dlo1 double mutants and identified seven unique zund mutants. These plants carried mutations in known regulators of SA synthesis (ICS1, ISOCHORISMATE SYNTHASE 1), perception (NPR1, NONEXPRESSOR OF PR GENES 1), or signaling (PAD4, PHYTOALEXIN DEFICIENT 4), indicating that a suppression of SA synthesis or SA responses reduces the growth tradeoff in high immunity dmr6-3 dlo1 mutants. Three other zund mutants carried a mutation in the same gene: MED15a (MEDIATOR 15a), a component of the MEDIATOR complex for transcription initiation. We investigate the function of MED15a in the growth-immunity tradeoff in detail, and find that around 80% of dmr6-3 dlo1-induced gene expression changes are genetically dependent on the integrity of two amino acids in the MED15a kinase-inducible (KIX) domain. I discuss the implications of this research for applications to breed for sustainable disease resistance in crops.

Plants have a dynamic immune system to protect themselves against pathogens. Recognition of a pathogen leads to the activation of this immune system, steered by different phytohormones. One of these, salicylic acid, regulates plant responses to biotrophic pathogens that thrive on living host tissue. Typical SA-mediated responses are the production of antimicrobial proteins and metabolites and the strengthening of the cell wall. These responses can occur both locally and systemically. Due to their nature, these responses cost energy and resources that cannot be invested in plant growth and development. This suppression also works the other way around: active growth and developmental processes suppress immunity. This mutual inhibition is called the growth-immunity tradeoff and is actively regulated by the plant. The research in this thesis is focused on the model plant Arabidopsis thaliana (thale cress), in which the SA content is controlled at the level of synthesis and catabolism. Two enzymes that catabolize SA through hydroxylation are the paralogous 2-oxoglutarate Fe(II)-dependent oxygenases DMR6/S5H (DOWNY MILDEW RESISTANT 6/SA 5-HYDROXYLASE) and DLO1/S3H (DMR6-LIKE OXYGENASE 1/SA 3-HYDROXYLASE). dmr6/dlo1 mutants have enhanced SA levels and therefore a constitutively active immune system and enhanced disease resistance. The high SA levels of double mutant plants cause hyperresistance but also dwarfism. On the other hand, overexpression of DMR6 or DLO1 leads to depletion of SA and thus enhanced susceptibility. We use the perturbed SA catabolism of the dmr6/dlo1 mutants and DMR6/DLO1 overexpression lines to investigate the SA-mediated growth-immunity tradeoff. We found that altered expression of DMR6 and/or DLO1 had major effects on the transcriptome that correlated to the plant’s SA content. We found that enhanced SA levels in dmr6/dlo1 mutants caused reduced photosynthetic efficiency and a sped up development and reduced SA levels in DMR6/DLO1 overexpression lines led to reduced pathogen-associated molecular pattern (PAMP)-triggered immune responses. We further identified a significant effect of the genetic background to perturbations in DMR6/DLO1 expression in different Arabidopsis accessions: several Arabidopsis accessions had a reduced growth tradeoff but retained high disease resistance. To systematically investigate the genetics behind regulation of the growth-immunity tradeoff, we further employed a forward genetics screen for restored growth and high resistance in dmr6-3 dlo1 double mutants and identified seven unique zund mutants. These plants carried mutations in known regulators of SA synthesis (ICS1, ISOCHORISMATE SYNTHASE 1), perception (NPR1, NONEXPRESSOR OF PR GENES 1), or signaling (PAD4, PHYTOALEXIN DEFICIENT 4), indicating that a suppression of SA synthesis or SA responses reduces the growth tradeoff in high immunity dmr6-3 dlo1 mutants. Three other zund mutants carried a mutation in the same gene: MED15a (MEDIATOR 15a), a component of the MEDIATOR complex for transcription initiation. We investigate the function of MED15a in the growth-immunity tradeoff in detail, and find that around 80% of dmr6-3 dlo1-induced gene expression changes are genetically dependent on the integrity of two amino acids in the MED15a kinase-inducible (KIX) domain. I discuss the implications of this research for applications to breed for sustainable disease resistance in crops.

Plants have a dynamic immune system to protect themselves against pathogens. Recognition of a pathogen leads to the activation of this immune system, steered by different phytohormones. One of these, salicylic acid, regulates plant responses to biotrophic pathogens that thrive on living host tissue. Typical SA-mediated responses are the production of antimicrobial proteins and metabolites and the strengthening of the cell wall. These responses can occur both locally and systemically. Due to their nature, these responses cost energy and resources that cannot be invested in plant growth and development. This suppression also works the other way around: active growth and developmental processes suppress immunity. This mutual inhibition is called the growth-immunity tradeoff and is actively regulated by the plant. The research in this thesis is focused on the model plant Arabidopsis thaliana (thale cress), in which the SA content is controlled at the level of synthesis and catabolism. Two enzymes that catabolize SA through hydroxylation are the paralogous 2-oxoglutarate Fe(II)-dependent oxygenases DMR6/S5H (DOWNY MILDEW RESISTANT 6/SA 5-HYDROXYLASE) and DLO1/S3H (DMR6-LIKE OXYGENASE 1/SA 3-HYDROXYLASE). dmr6/dlo1 mutants have enhanced SA levels and therefore a constitutively active immune system and enhanced disease resistance. The high SA levels of double mutant plants cause hyperresistance but also dwarfism. On the other hand, overexpression of DMR6 or DLO1 leads to depletion of SA and thus enhanced susceptibility. We use the perturbed SA catabolism of the dmr6/dlo1 mutants and DMR6/DLO1 overexpression lines to investigate the SA-mediated growth-immunity tradeoff. We found that altered expression of DMR6 and/or DLO1 had major effects on the transcriptome that correlated to the plant’s SA content. We found that enhanced SA levels in dmr6/dlo1 mutants caused reduced photosynthetic efficiency and a sped up development and reduced SA levels in DMR6/DLO1 overexpression lines led to reduced pathogen-associated molecular pattern (PAMP)-triggered immune responses. We further identified a significant effect of the genetic background to perturbations in DMR6/DLO1 expression in different Arabidopsis accessions: several Arabidopsis accessions had a reduced growth tradeoff but retained high disease resistance. To systematically investigate the genetics behind regulation of the growth-immunity tradeoff, we further employed a forward genetics screen for restored growth and high resistance in dmr6-3 dlo1 double mutants and identified seven unique zund mutants. These plants carried mutations in known regulators of SA synthesis (ICS1, ISOCHORISMATE SYNTHASE 1), perception (NPR1, NONEXPRESSOR OF PR GENES 1), or signaling (PAD4, PHYTOALEXIN DEFICIENT 4), indicating that a suppression of SA synthesis or SA responses reduces the growth tradeoff in high immunity dmr6-3 dlo1 mutants. Three other zund mutants carried a mutation in the same gene: MED15a (MEDIATOR 15a), a component of the MEDIATOR complex for transcription initiation. We investigate the function of MED15a in the growth-immunity tradeoff in detail, and find that around 80% of dmr6-3 dlo1-induced gene expression changes are genetically dependent on the integrity of two amino acids in the MED15a kinase-inducible (KIX) domain. I discuss the implications of this research for applications to breed for sustainable disease resistance in crops.

This work presents a fully integrated boost switched-capacitor regulator in 40 nm CMOS technology. In addition to using small MOS + MOM capacitors to reduce the area, the regulator utilizes a pseudo-6-bit analog-to-digital converter at the converter’s output to determine the driving capability needed. Combined with a 32-phase clock, this novel approach reduces control complexity, achieves small ripples, and shows a very fast transient response from zero to the maximum load of 6 mA, and vice versa, in 100 ps with output overshoot and undershoot not exceeding 4% of the regulator’s output voltage. A new Figure of Merit is developed to establish a basis for comparing fully integrated switched regulators’ transient response.

Most of the existing control schemes for power systems ensure stability only in the presence of constant loads and renewable energy sources. Motivated then by the inadequacy of the existing control strategies for power systems affected by time-varying loads and renewable energy sources, this article proposes two control schemes based on the well-known output regulation control methodology. The first one is designed based on the classical output regulation theory and addresses the so-called load frequency control (LFC) problem in the presence of time-varying uncontrolled power injections. Then, in order to also minimize the generation costs, we use an approximate output regulation method that solves numerically only the partial differential equation of the regulator equation and propose a controller based on this solution, minimizing an appropriate penalty function. An extensive case study shows the excellent performance of the proposed control schemes in realistic and critical scenarios.

The work focuses on a new mathematical formulation for the transfer function of a pulsating injection-based position observer, as the key point for its correct design. The proposed analysis exploits the modulation/demodulation control theory to derive the transfer function of the whole estimator in the Laplace domain. Magnetic iron saturation effects and cross–saturation between the dq-axes are taken into consideration in the observer design. To test the effectiveness of the new transfer function representation of the observer, it is used to synthesise two different regulators, namely by the direct synthesis and the internal model principle. An extensive experimental stage is included pointing to fully verify the accuracy of the proposed model and the theoretical considerations. A comparison with the existing mathematical model of the observer is also reported to show the improvement achievable in the position estimation by the proposed observer synthesis.

Mutations in superoxide dismutase 1 (SOD1) result in misfolding and aggregation of the protein, causing neurodegenerative amyotrophic lateral sclerosis (ALS). In recent years, several new SOD1 variants that trigger ALS have been identified, making it increasingly crucial to understand the SOD1 toxicity pathway in ALS. Here we used an integrated bioinformatics approach, including the Ingenuity Pathway Analysis (IPA) tool to analyze signaling pathways, regulators, functions, and network molecules of SOD1 with an emphasis on ALS. IPA toxicity analysis of SOD1 identified superoxide radicals’ degradation, apelin adipocyte, ALS, NRF2-mediated oxidative stress response, and sirtuin signaling as the key signaling pathways, while the toxicity of SOD1 is exerted via mitochondrial swelling and oxidative stress. IPA listed CNR1, APLN, BTG2, MAPK, DRAP1, NFE2L2, SNCA, and CG as the upstream regulators of SOD1. IPA further revealed that mutation in SOD1 results in hereditary disorders, including ALS. The exploration of the relationship between SOD1 and ALS using IPA unveiled SOD1-ALS pathway molecules. The gene ontology (GO) analysis of SOD1-ALS pathway molecules with ShinyGO reaffirmed that SOD1 toxicity results in ALS and neurodegeneration. The GO analysis further identified enriched biological processes, molecular functions, and cellular components for SOD1-ALS pathway molecules. The construction of a protein–protein interaction network of SOD1-ALS pathway molecules using STRING and further analysis of that network with Cytoscape identified ACTB followed by TP53, IL6, CASP3, SOD1, IL1B, APP, APOE, and VEGFA as the major network hubs. Taken together, our study provides insight into the molecular underpinning of SOD1’s toxicity in ALS.

Soft robots are intrinsically underactuated mechanical systems that operate under uncertainties and disturbances. In these conditions, this letter proposes two versions of PID-like control laws with a saturated integral action for the particularly challenging shape regulation task. The closed-loop system is asymptotically stabilized and matched constant disturbances are rejected using a very reduced amount of system information for control implementation. Stability is assessed on the underactuated dynamic model through the Invariant Set Theorem for two relevant classes of soft robots, i.e., elastically decoupled and elastically dominated soft robots. Extensive simulation results validate the proposed controllers.

Splice-modulating antisense oligonucleotides (ASOs) offer treatment options for rare neurological diseases, including those with very rare mutations, where patient-specific, individualized ASOs have to be developed. Inspired by the development of milasen, the 1 Mutation 1 Medicine (1M1M) and Dutch Center for RNA Therapeutics (DCRT) aim to develop patient-specific ASOs and treat eligible patients within Europe and the Netherlands, respectively. Treatment will be provided under a named patient setting. Our initiatives benefited from regulatory advice from the European Medicines Agency (EMA) with regard to preclinical proof-of-concept studies, safety studies, compounding and measuring benefit and safety in treated patients. We here outline the most important considerations from these interactions and how we implemented this advice into our plan to develop and treat eligible patients within Europe.

Магістерська дисертація включає до себе: пояснювальну записку на 134 сторінок, в тому числі 48 рисунків та 34 таблиці. На основі аналітичного огляду науково-технічної літератури визначено актуальність та основін напрямки дослідження транспортних систем. Сформуловано основні вимоги до електромеханічної транспортної системи системи автоматизованого комплексу металообробки. Визначено як найбільш перспективною система електропривода конвеєра побудовано по системі «перетворювач частоти – електродвигун» Під час виконання магістерської дисертації проведено тяговий розрахунок стрічкового конвеєра, визначено параметри схеми заміщення обраного двигуна. На основі отриманих математичних моделей елементів електромеханічної системи отримано модель для дослідження режимів роботи стрічкового конвеєра, проведено дослідження режимів її роботи . За результатами дослідження сформуловано рекомендації що до використання розроблених оптимальних регуляторів в транспортних системах лінії металообробки. The master's thesis includes: an explanatory note on 134 pages, including 48 figures and 34 tables. On the basis of an analytical review of the scientific and technical literature, the relevance and basis of the research direction of transport systems are determined. The basic requirements for the electromechanical transport system of the automated metalworking complex are formulated. Determined as the most promising conveyor electric drive system built according to the "frequency converter - electric motor" system During the execution of the master's thesis, the traction calculation of the belt conveyor was carried out, the parameters of the replacement scheme of the selected engine were determined. On the basis of the obtained mathematical models of the elements of the electromechanical system, a model was obtained for the study of the modes of operation of the belt conveyor, and the study of its modes of operation was carried out. Based on the results of the research, recommendations were formulated regarding the use of the developed optimal regulators in the transport systems of the metalworking line.

Datum: [2023-01-11]Nivå: Kandidatuppsats Företagsekonomi, 15 hpAkademi: Akademin för Ekonomi, Samhälle och Teknik, Mälardalens UniversitetFörfattare: Debora Marouki Kristena Samouie Ornina Gergeo[00/03/29] [99/03/13] [01/03/31]Titel: Förväntningar på revisorn - Finns det ett förväntningsgap mellanrevisorer och myndigheter, utifrån revisorns perspektiv?Handledare: Oksana FeicherNyckelord: Förväntningsgap, ekonomiska oegentligheter, intressentteori, revision,tillsynsmyndigheter.Forskningsfrågor: Förekommer det ett förväntningsgap mellan revisorer och myndighetervid upptäckandet av ekonomiska oegentligheter?Hur kan förväntningsgapet minka utifrån revisorns perspektiv?Syfte: Syftet med arbetet är att undersöka myndigheternas förväntningar pårevisorn vid upptäckandet av ekonomiska oegentligheter. Studien harvidare för avsikt att lyfta fram revisorernas uppfattning avförväntningarna samt undersöka revisorernas förslag till ett minskatförväntningsgap.Metod: Studien tillämpar en kvalitativ metod eftersom studien utgår frånrevisorns perspektiv och efterfrågar revisorns tankar, åsikter ocherfarenheter.Slutsats: Studien påvisar att revisorn inte är en avgörande aktör när det gällerupptäckandet av ekonomiska oegentligheter. Däremot visar studien påatt revisorn kan bidra till att motverka oegentligheter eftersom de kanupptäcka fel som kan förekomma i form av skattebrott ellerbokföringsbrott. Revisorerna anser sig själva vara en kvalitetsstämpelmedan myndigheterna anser att revisorn utövar tillsyn i företag. Detkan således konstateras att det finns ett förväntningsgap mellanrevisorer och myndigheter vid upptäckandet av ekonomiskaoegentligheter. Date: [2023-01-11]Level: Bachelor thesis in Business Administration, 15 hpInstitution: School of Business, Society and Engineering, Mälardalen UniversityAuthors: Debora Marouki Kristena Samouie Ornina Gergeo[00/03/29] [99/03/13] [01/03/31]Title: Expectations of the auditor - Is there an expectation gap betweenauditors and authorities, based on the auditor's perspective?Supervisor: Oksana FeicherKeywords: Expectation gap, financial irregularities, stakeholder theory, audit,regulators.Research questions: Is there an expectation gap between auditors and authorities whendiscovering financial realities? How can the expectation gap bereduced from the auditor's perspective?Purpose: The purpose of the study is to examine the authorities' expectations ofthe auditor when discovering financial irregularities. The study furtherintends to highlight the auditors' perception of expectations andexamine the auditors' proposals for a reduced expectation gap.Method: The study applies a qualitative method for studying based on theauditor's perspective and then the auditor's thoughts, opinions andexperiences.Conclusion: The results of the study shows that the auditor is not a decisive actorwhen it comes to the discovery of financial realities. On the other hand,the study shows that the auditor can contribute to preventingirregularities because they can detect errors that may occur in the formof tax or accounting violations. The auditors consider themselves to bea seal of quality, while the authorities consider the auditor to supervisecompanies. It can thus be stated that there is an expectation gapbetween auditors and authorities when discovering financialirregularities.

We compute explicitly the Goncharov regulator integral associated to $K_4$ classes on modular curves in terms of $L$-values of modular forms. We use this expression to connect it with the Beilinson regulator integral., Comment: In memoriam: Professor Yuri Ivanovich Manin; 37 pages

Flux-Weakening (F-W) methods based on feedback voltage regulation schemes are commonly employed for Interior Permanent Magnet Synchronous Motor (IPMSM) drive systems. Generally, the voltage reference magnitude in the voltage controller is lower than the maximum available voltage due to the margin imposed to prevent saturation of current regulators during transients. However, the margin should be kept as small as possible to avoid torque capability loss above the base speed and larger current consumption at a certain torque in F-W operation. The trade-off between F-W control bandwidth and the necessity of voltage margin has been reported in previous literature, but never analyzed in depth. In fact, F-W regulator design aiming at a certain bandwidth has been addressed by means of gain adaptation, but the choice of the target bandwidth remained as an open issue. In this paper, the crucial transient conditions which can cause the saturation of current regulators, specifically the reduction of input voltage and the fast acceleration of the drive, are considered. The input voltage reduction affects the inverters supplied by means of a diode rectifier during AC grid voltage drop and the fast acceleration is a very common transient condition leading the control in the F-W range. Both conditions are analyzed in terms of worst-case requirement of F-W control bandwidth vs. setpoint voltage margin and the proposed analytical modelling is verified by means of simulations and experiments. The findings can be applied in the design of auto-tuning procedures and design for high-reliability or safety-critical applications.

The role that seaweeds play as primary producers and ecosystems engineers in marine coastal ecosystems is widely acknowledged. Seaweeds, however, are also important drivers in the development of the blue bioeconomy due to their vast diversity of unique chemicals with a broad range of industrial and biotechnological applications. In tropical regions, seaweed production has been focused on a few species only, because of their hydrocolloids used in the food industry. There is a strong need to identify new applications of red seaweed species in other sectors such as aquaculture. Therefore, to diversify the culture of red seaweeds, more tropical species need to be investigated for their chemical composition and potential application in aquaculture, and then, to develop a method for a sustainable cultivation of new seaweed candidates and enhance their economic potential. Based on this context, we analyze the potential value of the red edible seaweed Acanthophora spp., an under-valued seaweed species which is naturally abundant in tropical countries, and Kappaphycus spp., a commercially valuable seaweed commonly used for polysaccharide extraction. The vast chemical diversity of seaweeds (polysaccharides, phytohormones, amino acids, and pigments) has led to research on a wide range of applications in aquaculture, including pathogen control, immunostimulant, antioxidant, bioremediation, feed, UV protectants, increase in seafood shelf life, animal colorant, and growth regulator for microalga culture. This review hopes to stimulate the interest among seaweed researchers to investigate other local seaweed species and seek greater added value of their biomass and chemical compounds and their applications in the aquaculture sector. Additionally, this information will help stakeholders to benefit from these two red seaweeds by contributing to the diversification of the blue bioeconomy in tropical countries.

Cryptocurrencies are becoming an exciting topic for legislative bodies, practitioners, media, and scholars with diverse academic backgrounds. The work identifies diversification benefits when cryptocurrencies are combined with the equity instruments from Visegrad Stock Exchanges. Furthermore, the results of the study explore financial and economic benefits for the investors of combining cryptocurrencies with equity stocks on the mixed portfolio. Three different independent experiments were conducted to observe diversification benefits generated from cryptocurrencies. Results from the two experiments show that cryptocurrencies employ higher portfolio risk and generate higher returns when they are involved with equity stocks portfolios. The first experiment indicates that cryptocurrencies reduce the risk level of the equity portfolios while increase average returns. Providing the equity portfolios with additional equity stocks lower the portfolio risk which is in line with the theoretical paradigms. Results indicate that cryptocurrencies must be seriously considered by the portfolio managers as an essential aspect of the portfolio diversification benefits. Future studies might raise the samples of selected portfolios with stocks from different stock indexes, to identify the problem from a broader perspective.

A combined chemo‐enzymatic synthesis/NMR‐based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of 13C‐labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the 13C‐labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non‐labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof‐of‐concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities., Repeating carbohydrate patterns are commonly found in Nature in extended oligosaccharides and polysaccharides. When recognized by protein receptors, dissecting the contribution of each repeating unit to the binding event is not easy. Here, the introduction of 13C‐labels at specific positions of a tri‐LacNAc repeating hexasaccharide has been used in STD‐HSQC NMR experiments to reveal the preferred binding epitopes for a panel of human galectins.

Introduction. The competitive advantage in the field of critical knowledge and technology exacerbates the problem of the effectiveness of intellectual activity and the means of its support in science, production and education. Such visual aids, formed by conceptual and graphic elements, such as concept maps, frames, structural logic diagrams, etc., contribute to the theoretical analysis and generalisation of the formed images and representations of learners. According to the degree of the development of these visual aids, the emphasis shifts from the function of visibility to the function of the organisation of activities. The term “visibility” (associated with the initial images of perception and representation) is substituted by the term “regulator” (focused on the organisation of further activities of the student). The hypothesis assumes the expediency of the development of conceptual and graphic means of visualisation in the form of visual didactic regulations, which are the subject of research.The present research aims: to discuss the problem of the creation of didactic regulations for educational activities; to study the development of conceptual-graphic means of visibility and factors for improving their functionality; to forecast the development of this type of means based on the visualisation of the logical-semantic modelling of knowledge; to clarify terminology and applied aspects; and to conduct experimental approbation in the conditions of distance learning.Methodology and research methods. The research methodology is based on the fundamental didactic principle of visualisation, which is necessary for the transition in the process of cognition from sensory perception to abstract thinking and contributes to the combination of abstract thinking with visualisation in teaching. The research methodology is also based on the method of logical-semantic modelling of knowledge and the following criteria for the study of conceptual-graphic means of visualisation: the application of the cognitive principles of knowledge representation; the use of universal instructional analysis activities to transform knowledge; the applicability of graphical representation of content. The methodology for the formation of didactic regulations included a visual presentation of the results of logical-semantic modelling of knowledge using universal educational actions and coordinate-matrix graphics. The method of experimental approbation of regulations in distance learning involved: the participation of students of four specialities and university teachers; a questionnaire survey of students; mastering, designing and using didactic regulations on the topic of experimental studies.Results and scientific novelty. The search on the databases of scientific documents of the Russian Academy of Education, the Electronic Scientific Library, Scopus, WOS and the Internet revealed the apparent lack of research and development of didactic regulations of a conceptual-graphic type. It was established that the main reason for the development of conceptual and graphic means of visualisation is the complexity of the tasks to be solved in science, production and education. It is demonstrated that the improvement of the functionality of conceptual and graphical tools is explained by the application of the principles of cognitive visual representation of knowledge and the method of logical-semantic modelling. The basic structures of the regulations were predicted and formed; the terminology of the research approach was clarified; the application of the tools for educational and project-based activities, interfaces of computer training programs is considered.Practical significance. The functionality of visual didactic regulators expands the potential of visibility and complements the tools of the teacher and the student. Moreover, they can be used in teaching technologies, research activities and design, when creating computer training programs.

Colorectal cancer is one of the leading causes of cancer-associated mortality across the worldwide. One of the major challenges in colorectal cancer is the understanding of the regulatory mechanisms of biological molecules. In this study, we aimed to identify novel key molecules in colorectal cancer by using a computational systems biology approach. We constructed the colorectal protein–protein interaction network which followed hierarchical scale-free nature. We identified TP53, CTNBB1, AKT1, EGFR, HRAS, JUN, RHOA, and EGF as bottleneck-hubs. The HRAS showed the largest interacting strength with functional subnetworks, having strong correlation with protein phosphorylation, kinase activity, signal transduction, and apoptotic processes. Furthermore, we constructed the bottleneck-hubs’ regulatory networks with their transcriptional (transcription factor) and post-transcriptional (miRNAs) regulators, which exhibited the important key regulators. We observed miR-429, miR-622, and miR-133b and transcription factors (EZH2, HDAC1, HDAC4, AR, NFKB1, and KLF4) regulates four bottleneck-hubs (TP53, JUN, AKT1 and EGFR) at the motif level. In future, biochemical investigation of the observed key regulators could provide further understanding about their role in the pathophysiology of colorectal cancer.

International audience; The yeast Candida albicans is primarily a commensal of humans that colonizes the mucosal surfaces of the gastrointestinal and genital tracts. Yet, C. albicans can under certain circumstances undergo a shift from commensalism to pathogenicity. This transition is governed by fungal factors such as morphological transitions, environmental cues for instance relationships with gut microbiota and the host immune system. C. albicans utilizes distinct sets of regulatory programs to colonize or infect its host and to evade the host defense systems. Moreover, an orchestrated iron acquisition mechanism operates to adapt to specific niches with variable iron availability. Studies on regulatory networks and morphogenesis of these two distinct modes of C. albicans growth, suggest that both yeast and hyphal forms exist in both growth patterns and the regulatory circuits are inter‐connected. Here, we summarize current knowledge about C. albicans commensal‐to‐pathogen shift, its regulatory elements and their contribution to human disease.

SIRT5 is a member of the sirtuin family of NAD(+)-dependent protein lysine deacylases implicated in a variety of physiological processes. SIRT5 removes negatively charged malonyl, succinyl, and glutaryl groups from lysine residues and thereby regulates multiple enzymes involved in cellular metabolism and other biological processes. SIRT5 is overexpressed in human breast cancers and other malignancies, but little is known about the therapeutic potential of SIRT5 inhibition for treating cancer. Here we report that genetic SIRT5 disruption in breast cancer cell lines and mouse models caused increased succinylation of IDH2 and other metabolic enzymes, increased oxidative stress, and impaired transformation and tumorigenesis. We, therefore, developed potent, selective, and cell-permeable small-molecule SIRT5 inhibitors. SIRT5 inhibition suppressed the transformed properties of cultured breast cancer cells and significantly reduced mammary tumor growth in vivo, in both genetically engineered and xenotransplant mouse models. Considering that Sirt5 knockout mice are generally normal, with only mild phenotypes observed, these data establish SIRT5 as a promising target for treating breast cancer. The new SIRT5 inhibitors provide useful probes for future investigations of SIRT5 and an avenue for targeting SIRT5 as a therapeutic strategy.

Graphical abstract, Highlights • Membraneless organelles (MLO) carry out a large number of functions within the cell. • LLPS databases focus on different aspects, representing a challenge for data analysis. • 9000 MLO-associated proteins were analyzed to get an overview of the MLO landscape. • Disorder, LC regions, globular domains and PTMs span a wide range across LLPS proteins. • Proteins associate with more MLOs feature a higher degree of disorder., In recent years, attention has been devoted to proteins forming immiscible liquid phases within the liquid intracellular medium, commonly referred to as membraneless organelles (MLO). These organelles enable the spatiotemporal associations of cellular components that exchange dynamically with the cellular milieu. The dysregulation of these liquid–liquid phase separation processes (LLPS) may cause various diseases including neurodegenerative pathologies and cancer, among others. Until very recently, databases containing information on proteins forming MLOs, as well as tools and resources facilitating their analysis, were missing. This has recently changed with the publication of 4 databases that focus on different types of experiments, sets of proteins, inclusion criteria, and levels of annotation or curation. In this study we integrate and analyze the information across these databases, complement their records, and produce a consolidated set of proteins that enables the investigation of the LLPS phenomenon. To gain insight into the features that characterize different types of MLOs and the roles of their associated proteins, they were grouped into categories: High Confidence MLO associated (including Drivers and reviewed proteins), Potential Clients and Regulators, according to their annotated functions. We show that none of the databases taken alone covers the data sufficiently to enable meaningful analysis, validating our integration effort as essential for gaining better understanding of phase separation and laying the foundations for the discovery of new proteins potentially involved in this important cellular process. Lastly, we developed a server, enabling customized selections of different sets of proteins based on MLO location, database, disorder content, among other attributes (https://forti.shinyapps.io/mlos/).

This paper presents a droop-based controller for grid-tied three-phase inverters. The controller allows to regulate the inverter output power while operating grid-tied, to support the local grid voltage while operating islanded, and to seamlessly transition into this latter mode of operation. Remarkably, the use of the traditional droop control scheme for per-phase power control would lead to unequal frequencies among the phase voltages, which is not acceptable. Instead, the proposed controller allows independent power references tracking at each of the phases of a three-phase inverter while grid-tied and a proper transition into the islanded operation. Per-phase power control is crucial for several services in modern smart power networks, like demand-response and distributed unbalance compensation. The paper also reports the stability analysis of the whole control system and outlines a procedure for the design of the involved regulators. Simulation and experimental results considering a laboratory-scale prototype are reported and discussed to validate the proposed controller.

Plant-microorganism interactions at the rhizosphere level have a major impact on plant growth and plant tolerance and/or resistance to biotic and abiotic stresses. Of particular importance for forestry and agricultural systems is the cooperative and mutualistic interaction between plant roots and arbuscular mycorrhizal (AM) fungi from the phylum Glomeromycotina, since about 80% of terrestrial plant species can form AM symbiosis. The interaction is tightly regulated by both partners at the cellular, molecular and genetic levels, and it is highly dependent on environmental and biological variables. Recent studies have shown how fungal signals and their corresponding host plant receptor-mediated signalling regulate AM symbiosis. Host-generated symbiotic responses have been characterized and the molecular mechanisms enabling the regulation of fungal colonization and symbiosis functionality have been investigated. This review summarizes these and other recent relevant findings focusing on the molecular players and the signalling that regulate AM symbiosis. Future progress and knowledge about the underlying mechanisms for AM symbiosis regulation will be useful to facilitate agro-biotechnological procedures to improve AM colonization and/or efficiency., This study was supported by grant (PID2020-115336GB-I00) funded by Spanish MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, by the “European Union”.

The forestry production sector uses several strategies to minimize post-planting seedling losses. Some practices can modulate characteristics of interest for plant growth and defense, including changes in the light exposure, reduced watering, fertilization, and chemical or mechanical stimulus. This work quantified morphophysiological changes on Schinus terebinthifolius and Cedrela fissilis seedlings resulting from the application of salicylic acid for eight weeks. The experimental design was completely randomized, composed of four treatments (0, 100, 200, and 300 mg L-1 of salicylic acid). The quantified variables included height, diameter, and dry matter mass of the root and aerial parts. Additionally, leaf area, root-cell electrolyte loss, lignin content in roots, and stem plus phenolic compounds were quantified. On aroeira seedlings, the height, aerial, and radicular dry matter masses and leaf area were reduced while the diameter and the lignin content increased directly as a function of salicylic acid doses. In cedro seedlings the dose of 100 mg L-1, however, resulted in a better balance of plant biomass and would, therefore, be the most indicated dose for the species. The application of salicylic acid for 8 weeks on seedlings of both species resulted in the most relevant morphophysiological modifications correlated with quality characteristics of seedlings of woody species.

Comparative analyses of growth regulatory mechanisms between Arabidopsis and maize revealed that even when the gene space is conserved, the translation of knowledge from model species to crops is not trivial. Based on these insights, we formulate future opportunities to improve the interpretation of curiosity driven research towards crop improvement.

Pre-mRNA processing is an essential mechanism for the generation of mature mRNA and the regulation of gene expression in eukaryotic cells. While defects in pre-mRNA processing have been implicated in a number of diseases their involvement in metabolic pathologies is still unclear. Here, we show that both alternative splicing and alternative polyadenylation, two major steps in pre-mRNA processing, are significantly altered in non-alcoholic fatty liver disease (NAFLD). Moreover, we find that Serine and Arginine Rich Splicing Factor 10 (SRSF10) binding is enriched adjacent to consensus polyadenylation motifs and its expression is significantly decreased in NAFLD, suggesting a role mediating pre-mRNA dysregulation in this condition. Consistently, inactivation of SRSF10 in mouse and human hepatocytes in vitro, and in mouse liver in vivo, was found to dysregulate polyadenylation of key metabolic genes such as peroxisome proliferator-activated receptor alpha (PPARA) and exacerbate diet-induced metabolic dysfunction. Collectively our work implicates dysregulated pre-mRNA polyadenylation in obesity-induced liver disease and uncovers a novel role for SRSF10 in this process.

Given the integration of the City of London into the single market for financial services in the European Union (EU), theories of transnational governance would expect the United Kingdom (UK) to favour close regulatory alignment with the EU27 post-Brexit to maximise market access and financial stability. Surprisingly, however, the UK has consistently demanded regulatory flexibility in financial services and has accepted reduced market access. We argue that the explanation is twofold. First, UK preferences reflect the need to balance the competing demands of elected officials, the financial industry and financial regulators. Second, drawing on a bureaucratic politics perspective, we suggest that UK preferences have been strongly shaped by the importance to UK regulators of retaining autonomy over high-status policy competences. This article contributes to the broader literature on the politics of financial regulation by highlighting the added value of incorporating a bureaucratic politics perspective when explaining financial regulatory preferences.

Background The PIM family kinases promote cancer cell survival and motility as well as metastatic growth in various types of cancer. We have previously identified several PIM substrates, which support cancer cell migration and invasiveness. However, none of them are known to regulate cellular movements by directly interacting with the actin cytoskeleton. Here we have studied the phosphorylation-dependent effects of PIM1 on actin capping proteins, which bind as heterodimers to the fast-growing actin filament ends and stabilize them. Methods Based on a phosphoproteomics screen for novel PIM substrates, we have used kinase assays and fluorescence-based imaging techniques to validate actin capping proteins as PIM1 substrates and interaction partners. We have analysed the functional consequences of capping protein phosphorylation on cell migration and adhesion by using wound healing and real-time impedance-based assays. We have also investigated phosphorylation-dependent effects on actin polymerization by analysing the protective role of capping protein phosphomutants in actin disassembly assays. Results We have identified capping proteins CAPZA1 and CAPZB2 as PIM1 substrates, and shown that phosphorylation of either of them leads to increased adhesion and migration of human prostate cancer cells. Phosphorylation also reduces the ability of the capping proteins to protect polymerized actin from disassembly. Conclusions Our data suggest that PIM kinases are able to induce changes in actin dynamics to support cell adhesion and movement. Thus, we have identified a novel mechanism through which PIM kinases enhance motility and metastatic behaviour of cancer cells. Graphical abstract

The paper presents two fuzzy logic control algorithms: type-1 and type-2. These two nonlinear techniques are used for adjust the speed control with a direct stator flux orientation control of a doubly fed induction motor. The effectiveness of the proposed control strategy is evaluated under different operating conditions such as of reference speed and for load torque step changes at nominal parameters and in the presence of parameter variation (stator resistance, rotor resistance and moment of inertia). The results of the simulation of the doubly fed induction motor velocity control have shown that fuzzy type-2 ensures better dynamic performances with respect to fuzzy type-1 control, even by parametric variations and external disturbances.

BackgroundThe relationship between quality and safety regulation and resilience in healthcare has received little systematic scrutiny. Accordingly, this study examines the introduction of a new regulatory framework (the Quality Improvement Regulation) in Norway that aimed to focus on developing the capacity of hospitals to continually improve quality and safety. The overall aim of the study was to explore the governmental rationale and expectations in relation to the Quality Improvement Regulation, and how it could potentially influence the management of resilience in hospitals. The study applies resilience in healthcare and risk regulation astheoretical perspectives.MethodsThedesignis a single embedded case study, investigating the Norwegian regulatory healthcare regime. Data was collected by approaching three regulatory bodies through formal letters, asking them to provide internal and public documents, and by searching through open Internet-sources. Based on this, we conducted a document analysis, supplemented by interviews with seven strategic informants in the regulatory bodies.ResultsTherationalefor introducing the Quality Improvement Regulation focused on challenges associated with implementation, lack of management competencies; need to promote quality improvement as a managerial responsibility. Some informants worried that the generic regulatory design made it less helpful for managers and clinicians, others claimed a non-detailed regulation was key to make it fit all hospital-contexts. The Government expected hospital managers to obtain an overview of risks and toadaptrisk management and quality improvement measures to their specific context and activities.ConclusionsBased on the rationale of making the Quality Improvement Regulation flexible to hospital context, encouraging the ability to anticipate local risks, along with expectations about the generic design as challenging for managers and clinicians, we found that the regulators did consider work as done as important when designing the Quality Improvement Regulation. These perspectives are in line with ideas of resilience. However, the Quality Improvement Regulation might be open for adaptation by the regulatees, but this may not necessarily mean that it promotes or encourages adaptive behavior in actual practice. Limited involvement of clinicians in the regulatory development process and a lack of reflexive spaces might hamper quality improvement efforts.

Amrita K Cheema,1 Prabhjit Kaur,1 Amina Fadel,2 Noura Younes,3 Mahmoud Zirie,4 Nasser M Rizk2,5 1Department of Oncology, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, DC, USA; 2Biomedical Sciences Department, College of Health Sciences and Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; 3Clinical Chemistry Lab, Hamad Medical Corporation, Doha, Qatar; 4Endocrine Department, Hammad Medical Corporation, Doha, Qatar; 5Physiology Department, Mansoura Faculty of Medicine, Mansoura, EgyptCorrespondence: Nasser M RizkBiomedical Sciences Department, College of Health Sciences, Biomedical Research Center, QU Health, Qatar University, Doha, QatarEmail nassrizk@qu.edu.qaObjective: The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers.Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database.Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers.Conclusion: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities.Keywords: type 2 diabetes mellitus, pathway analysis, regulators, biomarkers, disorders, bioinformatics

Current bacterial RNA switches suffer from lack of versatile inputs and are difficult to engineer. We present versatile and modular RNA switches that are trans‐encoded and based on tRNA‐mimicking structures (TMSs). These switches provide a high degree of freedom for reengineering and can thus be designed to accept a wide range of inputs, including RNA, small molecules, and proteins. This powerful approach enables control of the translation of protein expression from plasmid and genome DNA., Switch‐hitter: A bacterial genetic switch that accepts RNAs, small molecules, and proteins as inputs was developed based on a tRNA‐mimicking structure. The switch is trans‐encoded, which makes manipulation of the target mRNA redundant. It is stable to RNase, shows a strong dynamic response, and exhibits a high level of orthogonality.

This paper represents the initial phase of a larger project being developed by the “Media, communication policy and democracy in the European Union” research group, which is currently working on the study “Communication policies, SVOD platforms and values education for minors in the single digital market (2020-2022)”. We wish to pursue in this study that, beyond technological considerations, it is necessary to expand the scope of child protection by establishing mutual collaboration between regulators, distributors and video on demand services, as well as consumers and parents’ organisations, in an effort to further enhance cooperation and mutual understanding (European Regulators Group for Audiovisual Media Services, 2017b, p. 75). It is for this reason that we believe that the academic sphere can also be invited into this wide-ranging discussion on child protection to contribute reflections on a key aspect: audiovisual and media education, an essential pillar of protection in addition to filters, external limits, and electronic labelling. We thus uphold a vision that not only considers the “digital stuff” but also highlights the need for “ethos stuff” (Goggin, 2008, p.89). In this respect, we have considered it essential a literature review on the concept of media literacy. Secondly, our qualitative methodology involves an analysis of the instructions issued by the European Union and their implementation in Spain. In this stage, we have conducted desk research based on a narrative analysis of the documents and programs of different institutions in order to chart the evolution of the question in recent years, at a time when the digital environment has changed more quickly than ever before. This same type of analysis is also conducted on the initiatives of European and Spanish companies to determine whether they are implementing child protection strategies., Este artigo representa a fase inicial de um projeto mais vasto conduzido pelo grupo de investigação “Media, política de comunicação e democracia na União Europeia” que está atualmente a desenvolver o estudo “Políticas de comunicação, plataformas SVOD e educação de valores para menores no mercado único digital (2020-2022)”. Neste estudo, pretendemos explorar a ideia de que, além das considerações tecnológicas, é necessário alargar o âmbito da proteção infantil, estabelecendo colaboração mútua entre entidades reguladoras, distribuidores e serviços de vídeo on demand, bem como organizações de consumidores e de pais, num esforço para melhorar ainda mais a cooperação e o entendimento mútuo (Grupo Europeu de Reguladores dos Serviços de Comunicação Audiovisuais, 2017b, p. 75). Tendo por base este objetivo, consideramos que a esfera académica também pode ser convidada para este abrangente debate sobre proteção infantil, a fim de contribuir para um aspeto fundamental: a educação audiovisual e mediática como um pilar essencial de proteção, além de filtros, limites externos e rotulagem eletrónica. Assim, defendemos uma visão que considera não apenas os aspetos digitais (digital stuff), mas também destaca a necessidade de aspetos éticos (ethos stuff) (Goggin, 2008, p.89). A esse respeito, é essencial uma revisão da literatura sobre o conceito de literacia mediática. A metodologia qualitativa envolve uma análise das indicações da União Europeia e a sua implementação em Espanha. Nesta fase, realizámos pesquisas de dados secundários com base numa análise narrativa dos documentos e programas de diferentes instituições, a fim de mapear a evolução da questão nos últimos anos, num momento em que o ambiente digital mudou muito rapidamente. Este tipo de análise também é conduzido nas iniciativas de empresas europeias e espanholas, no sentido de determinar se estão a implementar estratégias de proteção à criança.

Background: Signaling pathways including gene silencing, cellular differentiation, homeostasis, development and apoptosis are regulated and controlled by a wide range of miRNAs. Objective: Due to their potential binding sites in human-protein coding genes, many studies have also linked their altered expressions in various cancer types making them tumor suppressors agents. Methods: Moreover, each miRNA is predicted to have many mRNA targets indicating their extensive regulatory role in cell survival and developmental processes. Nowadays, diagnosis of early cancer stage development is now dependent on variable miRNA expression levels as potential oncogenic biomarkers in validating and targeting microRNAs for cancer therapy. Results: As the majority of miRNA, transcripts are derived from RNA polymerase II-directed transcription, stress response could result on a general reduction in the abundance of these transcripts. Over expression of various microRNAs have lead to B cell malignancy, potentiated KrasG12Dinduced lung tumorigenesis, chronic lymphocytic leukemia, lymphoproliferative disease and autoimmunity. Conclusion: Altered miRNA expressions could have a significant impact on the abundance of proteins, making them attractive candidates as biomarkers for cancer detection and important regulators of apoptosis.

Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data. Cytochrome P450 family 2 subfamily c polypeptide 70 (CYP2C70) was recently proposed to catalyze the formation of rodent-specific muricholic acids (MCAs). With CRISPR/Cas9-mediated somatic genome editing, we generated an acute hepatic Cyp2c70 knockout mouse model (Cyp2c70ako) to clarify the role of CYP2C70 in BA metabolism in vivo and evaluate whether its activity modulates effects of pharmacologic FXR activation on cholesterol homeostasis. In Cyp2c70ako mice, chenodeoxycholic acid (CDCA) increased at the expense of βMCA, resulting in a more hydrophobic human-like BA pool. Tracer studies demonstrated that, in vivo, CYP2C70 catalyzes the formation of βMCA primarily by sequential 6β-hydroxylation and C7-epimerization of CDCA, generating βMCA as an intermediate metabolite. Physiologically, the humanized BA composition in Cyp2c70ako mice blunted the stimulation of fecal cholesterol disposal in response to FXR activation compared with WT mice, predominantly due to reduced stimulation of transintestinal cholesterol excretion. Thus, deletion of hepatic Cyp2c70 in adult mice translates into a human-like BA pool composition and impacts the response to pharmacologic FXR activation. This Cyp2c70ako mouse model may be a useful tool for future studies of BA signaling and metabolism that informs human disease development and treatment.

International audience; A shunt regulator was designed to meet the specifications for the serial powering of the CMOS pixel detector modules in compatibility with the next upgrade of the ATLAS detector. Serial powering greatly increases the system's power efficiency when compared to a parallel powering scheme and allows for significant material budget savings in the power cabling. In such a scheme, each pixel detector chip is powered by a shunt regulator that takes in a constant current and produces a regulated output voltage relative to the module's potential ground. The proposed regulator has a modular structure. Each regulator module consists of a shunt regulation submodule followed by a low-dropout voltage regulation submodule and is designed to deliver a nominal output current of 10 mA. The regulator module's schematic is presented along with a theoretical study and stability analysis. A test chip was designed in the 0.18-μm CMOS technology containing one main shunt regulator composed of 126 modules, as well as two separate regulators each composed of one single module. The characterization measurements show a correct dc startup for various load conditions, as expected by simulations. The output voltage of a single module is regulated with a precision

Made available in DSpace on 2020-12-10T19:55:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 In this manuscript, a method for designing Takagi-Sugeno (T-S) fuzzy discrete-time regulators based on linear matrix inequalities (LMIs) is proposed to control the variation of the knee joint angle movement of paraplegic patients through electrical stimulation. A simple method for discretizing nonlinear systems described by T-S fuzzy models is used. The control strategy is applied for a paraplegic volunteer and a healthy one. The results and analysis show that the controlled system attended the design specifications for small values of the sample time considered for the discretization. Univ Estadual Londrina, Dept Elect Engn, BR-86057970 Londrina, Parana, Brazil Univ Estadual Paulista, Dept Elect Engn, Campus Ilha Solteira, BR-15385000 Ilha Solteira, Brazil Univ Estadual Paulista, Dept Elect Engn, Campus Ilha Solteira, BR-15385000 Ilha Solteira, Brazil

The main aim of the present systematic review was to summarize the most frequently used telomerase regulators with an impact on aging and cancer that are referred to in in vitro and in vivo studies. For this purpose, a systematic review of the available literature on telomerase regulators referred to in articles from PubMed and Scopus libraries published from 2002 to 2021 and in accordance with PRISMA 2020 criteria, was conducted. Articles were included if they met the following criteria: They referred to telomerase modulators in aging and in cancer and were in vitro and/or in vivo studies, while studies that did not provide sufficient data or studies not written in English were excluded. In the present systematic review, 54 publications were included, of which 29 were full-text published studies, 11 were full-text reviews, 10 structure-based design studies and 4 abstracts are reported in this review. Telomerase regulators were then categorized as synthetic direct telomerase inhibitors, synthetic indirect telomerase inhibitors, synthetic telomerase activators, natural direct telomerase activators, natural telomerase inhibitors and natural indirect telomerase activators, according to their origin and their activity. On the whole, as demonstrated herein, telomerase regulators appear to be promising treatment agents in various age-related diseases. However, further in vivo and in vitro studies need to be performed in order to clarify the potentiality of telomerase as a therapeutic target. Title in WoS: tau elomerase inhibitors and activators in aging and cancer: A systematic review

MSc (Enviromental Management with Waste Management), North-West University, Potchefstroom Campus Waste Management Licensing (WML) is one of the environmental management policy instruments provided for in the National Environmental Management Waste Act (59 of 2008), as well as the National Waste Management Strategy. The WML application process is sometimes viewed as an obstacle, due to the perceived lengthy and bureaucratic nature of environmental impact assessment (EIA) process supporting the application. The value of the environmental assessment instruments has been scrutinized by different role players, leading to the desire to understand the benefits of undertaking these processes. Some recent research has been conducted by Roos et al. (2020) on the benefits of EIA for society and Cilliers et al. (2020) for government, both focusing on the perceptions of regulators within the South African context. However, no research has been done to understand the perceived benefits of waste management licensing, specifically, for society. The aim of this research is to determine the potential and realized benefits of waste management licensing for society as perceived by regulators. A semi-structured questionnaire was distributed to 62 provincial officials responsible for reviewing WML applications. They were requested to reflect on (i) the potential benefits of WML for society, (ii) the actual, realized benefits of WML for society, and (iii) means of bridging the gap between actual and potential benefits. Responses were received from 21 respondents, representing all nine provinces in South Africa. Reported benefits were discussed in accordance with the National Framework for Sustainable Development (NFSD); and top perceived potential and actual benefits were ranked according to their frequency of mention. The potential and actual benefits of WML for society as perceived by regulators leaned towards encouraging development that does not compromise ecosystem services, as well as exercising the constitutional right to a safe environment. Participants included climate change and health impact mitigation as additional potential benefits of WML (which was not included in this research). Improving education and awareness and an inclusive waste management licensing process were suggested as means of closing the gap between potential and actual benefits of WML for society. Masters

Тема выпускной квалификационной работы: Совершенствование государственного управления в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ Ð½Ð° примере Роскомнадзора. Объектом исследования является государственное управление в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ . Предметом исследования является деятельность уполномоченного органа в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ . Целью выпускной̆ квалификационной̆ работы является разработка предложений по совершенствованию текущего государственного управления в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , а также обзор деятельности Ð³Ð¾ÑÑƒÐ´Ð°Ñ€ÑÑ‚Ð²ÐµÐ½Ð½Ñ‹Ñ Ð¾Ñ€Ð³Ð°Ð½Ð¾Ð², Ñ€ÐµÐ³ÑƒÐ»Ð¸Ñ€ÑƒÑŽÑ‰Ð¸Ñ ÐºÐ¾Ð½Ñ‚Ñ€Ð¾Ð»ÑŒÐ½Ð¾-надзорную деятельность за обработкой Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , анализ деятельности уполномоченного органа. Метод проведения выпускной квалификационной работы: анализ текущего государственного регулирования в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , анализ деятельности уполномоченного органа по защите прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , выявление направлений совершенствования, предложения мер, Ð½Ð°Ð¿Ñ€Ð°Ð²Ð»ÐµÐ½Ð½Ñ‹Ñ Ð½Ð° совершенствование государственного управления в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ .В результате предложены меры по внесению изменений в Федеральное Законодательство, в нормативно-правовые акты уполномоченного органа, а также предложен проект положения о новом отделе «по работе с субъектами Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ Â» в Управлении Федеральной Службы по контролю (надзору) в сфере связи, Ð¸Ð½Ñ„Ð¾Ñ€Ð¼Ð°Ñ†Ð¸Ð¾Ð½Ð½Ñ‹Ñ Ñ‚ÐµÑ Ð½Ð¾Ð»Ð¾Ð³Ð¸Ð¸Ì† и Ð¼Ð°ÑÑÐ¾Ð²Ñ‹Ñ ÐºÐ¾Ð¼Ð¼ÑƒÐ½Ð¸ÐºÐ°Ñ†Ð¸Ð¸Ì†. Реализация мер по совершенствованию государственного управления в сфере защиты прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ Ð¿Ð¾Ð²Ð»ÐµÑ‡ÐµÑ‚ за собой уменьшений количества правонарушений ÑÐ²ÑÐ·Ð°Ð½Ð½Ñ‹Ñ Ñ незаконной обработкой Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , повышение уровня осведомленности граждан как субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ , подготовка кадров для государственной службы в уполномоченном органе по защите прав субъектов Ð¿ÐµÑ€ÑÐ¾Ð½Ð°Ð»ÑŒÐ½Ñ‹Ñ Ð´Ð°Ð½Ð½Ñ‹Ñ ., The topic of the final qualifying work: Improvement of state administration in the field of protection of the rights of personal data subjects (by the example of the activities of the Roskomnadzor). The subject of the study is public administration in the field of protection of the rights of personal data subjects. The purpose of the final qualifying work is to analyze the current state administration in the field of protection of the rights of personal data subjects, as well as to review the activities of state bodies regulating control and supervisory activities over the processing of personal data, the activities and measures of influence of the authorized body, with further development of proposals aimed at improving their effectiveness. Methodology of the final qualifying work: analysis of the current state regulation in the field of protection of the rights of personal data subjects, analysis of the activities of the Federal Service for Control (Supervision) in the field of communications, Information Technology and mass Communications as the authorized body for the protection of the rights of personal data subjects, identification of areas of improvement, proposal of measures aimed at improving public administration in the field of protection of the rights of personal data subjects. As a result of the final qualifying work, measures were proposed to amend Federal Legislation, regulatory legal acts of the authorized body, as well as a draft regulation on a new department "for working with personal data subjects" in the Department of the Federal Service for Control (Supervision) in the Field of Communications, Information Technology and Mass Communications.The implementation of measures to improve the efficiency of public administration in the field of protection of the rights of personal data subjects will entail a reduction in the number of offenses related to the illegal processing of personal data, raising awareness of citizens as personal data subjects, training personnel for public service in the authorized body for the protection of the rights of personal data subjects.

Distributed model predictive control (DMPC) concerns how to online control multiple robotic systems with constraints effectively. However, the nonlinearity, nonconvexity, and strong interconnections of dynamic system models and constraints can make the real-time and real-world DMPC implementations nontrivial. Reinforcement learning (RL) algorithms are promising for control policy design. However, how to ensure safety in terms of state constraints in RL remains a significant issue. This paper proposes a barrier function-based safe reinforcement learning algorithm for DMPC of nonlinear multi-robot systems under state constraints. The proposed approach is composed of several local learning-based MPC regulators. Each regulator, associated with a local system, learns and deploys the local control policy using a safe reinforcement learning algorithm in a distributed manner, i.e., with state information only among the neighbor agents. As a prominent feature of the proposed algorithm, we present a novel barrier-based policy structure to ensure safety, which has a clear mechanistic interpretation. Both simulated and real-world experiments on the formation control of mobile robots with collision avoidance show the effectiveness of the proposed safe reinforcement learning algorithm for DMPC.

MSc (Environmental Management), North-West University, Potchefstroom Campus Environmental Impact Assessment (EIA) is an internationally recognised and globally implemented tool used to appraise developmental projects. The benefits of EIA have been widely reported in the academic literature and environmental management practice. EIA is applauded as a decision making and planning tool which can enable the identification, management, reduction and/or elimination of negative impacts and risks of proposed developments. In addition to these benefits, EIA is also recognised as a mechanism that promotes learning. These learning outcomes may result in transformation of personal values, standards, policy, and practise. Given this potential, the investigation of learning through regulator participation in the South African EIA process was adopted as a focus for this study. Public service organisations and their employees such as regulators, are subject to significant pressure to perform their duties capably and efficiently within the constraints of the public administrative structure. In the context of the EIA process, government organisations and regulators are considered to lack institutional memory and regulatory efficiency. However, it has been reported that public service organisations have the potential to learn, and organisational learning concepts could be utilised to identify this. This study aimed to investigate the influence of EIA participation on organisational learning for both competent and commenting regulators involved in EIA processes of renewable energy projects. A qualitative approach was taken for the study, where a total of 14 participants were interviewed through the use of semi-structured interview questions. The results were sorted and coded manually using thematic analysis techniques. The results presented the regulators’ perception of learning outcomes gained through participation in renewable energy EIA projects. The findings of this study showed that regulators gained primarily single-loop learning outcomes at both national and provincial levels. Evidence of double-loop learning was possible mainly through collaborative engagements internally and externally. This study also found evidence of triple-loop learning for two participants; however, these outcomes could not be attributed to the rapid advances made in renewable energy project implementation. Furthermore, this study found that changes in the strategic focus of public organisations are constrained by the bureaucratic structure of the public organisation, thereby restricting organisational learning. Masters

Single-cell (sc) omics has become a powerful tool to unravel a tissue’s cell landscape across health and disease. In recent years, sc transcriptomic interrogation has been applied to a variety of tooth tissues of both human and mouse, which has considerably advanced our fundamental understanding of tooth biology. Now, an overarching and integrated bird’s-view of the human and mouse tooth sc transcriptomic landscape would be a powerful multifaceted tool for dental research, enabling further decipherment of tooth biology and development through constantly progressing state-of-the-art bioinformatic methods as well as the exploration of novel hypothesis-driven research. To this aim, we re-assessed and integrated recently published scRNAsequencing datasets of different dental tissue types (healthy and diseased) from human and mouse to establish inclusive tooth sc atlases, and applied the consolidated data map to explore its power. For mouse tooth, we identified novel candidate transcriptional regulators of the ameloblast lineage. Regarding human tooth, we provide support for a developmental connection, not advanced before, between specific epithelial compartments. Taken together, we established inclusive mouse and human tooth sc atlases as powerful tools to potentiate innovative research into tooth biology, development and disease. The maps are provided online in an accessible format for interactive exploration. Funding This work was supported by grants from the KU Leuven Research Fund and from the FWO (G061819N). LH is an FWO PhD fellow (1S84718N). Acknowledgments Computational resources for all sc transcriptome analyses were provided by the ‘Vlaams Supercomputer Centrum’ (VSC), managed by the Fund for Scientific Research (FWO) - Flanders (Belgium). Certain figures were created using BioRender.com or GraphPad Prism version 9.3.1 for macOS. Authors also thank the other members of the Laboratory of Tissue Plasticity in Health and Disease (KU Leuven) for their input.