Diverse classes of constraints enable broader applicability of a linear programming-based dynamic metabolic modeling framework

Current metabolic modeling tools suffer from a variety of limitations, from scalability to simplifying assumptions, that preclude their use in many applications. We recently created a modeling framework, Linear Kinetics-Dynamic Flux Balance Analysis (LK-DFBA), that addresses a key gap: capturing metabolite dynamics and regulation while retaining a potentially scalable linear programming structure. Key to this framework’s success are the linear kinetics and regulatory constraints imposed on the system. However, while the linearity of these constraints reduces computational complexity, it may not accurately capture the behavior of many biochemical systems. Here, we developed three new classes of LK-DFBA constraints to better model interactions between metabolites and the reactions they regulate. We tested these new approaches on several synthetic and biological systems, and also performed the first-ever comparison of LK-DFBA predictions to experimental data. We found that no single constraint approach was optimal across all systems examined, and systems with the same topological structure but different parameters were often best modeled by different types of constraints. However, we did find that when genetic perturbations were implemented in the systems, the optimal constraint approach typically remained the same as for the wild-type regardless of the model topology or parameterization, indicating that just a single wild-type dataset could allow identification of the ideal constraint to enable model predictivity for a given system. These results suggest that the availability of multiple constraint approaches will allow LK-DFBA to model a wider range of metabolic systems.

Silencing of ATP Synthase β Impairs Egg Development in the Leafhopper Scaphoideus titanus, Vector of the Phytoplasma Associated with Grapevine Flavescence Dorée

Scaphoideus titanus (Hemiptera: Cicadellidae) is the natural vector of Flavescence dorée phytoplasma, a quarantine pest of grapevine with severe impact on European viticulture. RNA interference (RNAi) machinery components are present in S. titanus transcriptome and injection of ATP synthase β dsRNAs into adults caused gene silencing, starting three days post injection (dpi) up to 20 dpi, leading to decrease cognate protein. Silencing of this gene in the closely related leafhopper Euscelidiusvariegatus previously showed female sterility and lack of mature eggs in ovaries. Here, alteration of developing egg morphology in S. titanus ovaries as well as overexpression of hexamerin transcript (amino acid storage protein) and cathepsin L protein (lysosome proteinase) were observed in dsATP-injected females. To evaluate RNAi-specificity, E.variegatus was used as dsRNA-receiving model-species. Different doses of two sets of dsRNA-constructs targeting distinct portions of ATP synthase β gene of both species induced silencing, lack of egg development, and female sterility in E. variegatus, indicating that off-target effects must be evaluated case by case. The effectiveness of RNAi in S. titanus provides a powerful tool for functional genomics of this non-model species and paves the way toward RNAi-based strategies to limit vector population, despite several technical and regulatory constraints that still need to be overcome to allow open field application.

Supporting Decommissioning/Conversion of Offshore Structures Applying Innovative Technological Solution INSURE project

Companies that work in the decommissioning of platforms need tools to make smarter and informed business decisions, manage and analyse business data, increase the security of workers and operate under strict environmental protection regulations. INSURE aims at assessing the feasibility of a new service to support the decommissioning of offshore installations by means of technological innovation made available throughout each process’ step. In order to accomplish this, the project gathers high-impact Italian companies bringing together the best applicable technological and scientific know-how. INSURE foresees to combine these know-hows and create a novel tool at the service of the industry to promote a better and safer approach to the operations. Targets of the INSURE project are improving workers’ safety, enhancing environmental monitorings, increasing operations’ efficiency, reducing operational costs, offering a route for future sustainability. Project targets can be achieved through the realisation of an augmented virtual reality platform (AVRP) that will be operated in support of the decommissioning process where the data acquired/transmitted by a plurality of sensors will converge. A fleet control tool integrates information from sensors installed on autonomous aerial and underwater vehicles making use of the Global Satellite Navigation Systems (GSNS) and Satellite Communications (SatCom). The convergence of top-notch technologies (augmented/virtual reality, 3D, robotics, sensors, 5G and Satellite services), together with a cloud of infrastructure, enables a fast and complete access to real-time data at very high resolution. The proposal aims to bring the actual data and information access from the Internet of Things to the Internet of Knowledge paradigm. Confrontation with national and international possible end-users produced a set of user requirements guiding the design of a feasibility study for the realisation of one specific product. The study also includes the evaluation of economic, non-economic viability and possible regulatory constraints to its realisation. The INSURE feasibility study creates the intellectual background for the further step of the process: the realisation and development of a pilot project tailored for the purpose. This combined use of novel technologies represents an innovative integrated approach applied to the management of offshore structures undergoing decommissioning or reconfiguration for other purposes. In addition, it also involves the promotion of sustainable opportunities for commercial, social and educational exploitation of areas and assets (including, for example, the ambit of eco-tourism, renewable energies, carbon capture and storage).

Regulatory Restrictions Across U.S. Protein Supply Chains

Food regulations protect consumer health, mitigate environmental concerns, and promote animal welfare, but they can also hinder innovation, limit entrepreneurship, and generate higher consumer prices. This study examines the number of federal and state regulatory restrictions affecting the beef, pork, poultry, sheep, goat, and seafood industries, including processing, wholesale distribution, and retail sales. We also examine state regulatory heterogeneity associated with animal protein products. Our results suggest that protein supply chains have become subject to tens of thousands of regulatory constraints over the past half-century. We also find substantial heterogeneity in the number of state restrictions associated with animal production, indicative of large differences in the amount of administrative law across states. Results highlight that the patchwork approach of U.S. food policy creates overlapping, cumbersome guidelines for manufacturers, and given the interconnectivity of modern food supply chains, the framework can create additional hurdles for interstate commerce.

Metabolic Pathway Analysis in the Presence of Biological Constraints

Metabolic pathway analysis is a key method to study a metabolism in its steady state, and the concept of elementary fluxes (EFs) plays a major role in the analysis of a network in terms of non-decomposable pathways. The supports of the EFs contain in particular those of the elementary flux modes (EFMs), which are the support-minimal pathways, and EFs coincide with EFMs when the only flux constraints are given by the irreversibility of certain reactions. Practical use of both EFMs and EFs has been hampered by the combinatorial explosion of their number in large, genome-scale systems. The EFs give the possible pathways in a steady state but the real pathways are limited by biological constraints, such as thermodynamic or, more generally, kinetic constraints and regulatory constraints from the genetic network. We provide results on the mathematical structure and geometrical characterization of the solution space in the presence of such biological constraints (which is no longer a convex polyhedral cone or a convex polyhedron) and revisit the concept of EFMs and EFs in this framework. We show that most of the results depend only on very general properties of compatibility of constraints with vector signs: either sign-invariance, satisfied by regulatory constraints, or sign-monotonicity (a stronger property), satisfied by thermodynamic and kinetic constraints. We show in particular that the solution space for sign-monotone constraints is a union of particular faces of the original polyhedral cone or polyhedron and that EFs still coincide with EFMs and are just those of the original EFs that satisfy the constraint, and we show how to integrate their computation efficiently in the double description method, the most widely used method in the tools dedicated to EFs computation. We show that, for sign-invariant constraints, the situation is more complex: the solution space is a disjoint union of particular semi-open faces (i.e., without some of their own faces of lesser dimension) of the original polyhedral cone or polyhedron and, if EFs are still those of the original EFs that satisfy the constraint, their computation cannot be incrementally integrated into the double description method, and the result is not true for EFMs, that are in general strictly more numerous than those of the original EFMs that satisfy the constraint.

Impact of Non-Financial Factors on Performance of Small and Medium Scale Enterprises of Furniture Industry in Moratuwa, Sri Lanka

Small and Medium Enterprises in any nation are blessed with the ability to become the backbone of the domestic economy and the sustainability. Therefore, they must concern about the factors which are affecting their performance. Many studies have been conducted by highlighting the financial factors that affect the performance of small and medium enterprises. Furniture industry is also embodied with number of small and medium enterprises around Sri Lanka. But still it is held the reputation in Moratuwa city. As an industry, small and medium enterprises are not sufficiently aware of non-financial factors which affect their performance and struggle to identify the impact of non-financial factors and how they could avoid the barriers from non-financial factors. Though the recent governments and regulatory bodies have designed policies and strategies to encourage small and medium enterprises by providing financial facilities, the information and the knowledge regarding non-financial factors are not sufficient. The purpose of this study is to identify the impact of non-financial factors on performance of Furniture industry in Moratuwa, Sri Lanka. After a comprehensive literature review, Input constraints, Regulatory Constraints, Technology constraints, Infrastructure constraints and Threats of Substitute products are identified as the independent variables of the study. Data collection was done using a structured questionnaire with 30 questions of Likert scales from the selected sample of 100 Furniture small and medium enterprises located in Moratuwa area. The analysis was carried out performing tests on descriptive statistics, validity, reliability, correlation, and regression analyses, and it is empirically supported that there is a significant impact of input constraints and infrastructure constraints on performance of Furniture industry in Moratuwa, Sri Lanka. Thereby, the findings would help the authorities and policy makers to take necessary actions to accomplish fu

MONETARY CIRCULATION AND BANKS IN THE INTERPRETATION OF THE MAIN ECONOMIC SCHOOLS

The topicality of the research lies in the fact that the long-term evolution of financial markets, reinforced by global transformations, has led to the development of convergent processes in banking activities in the presence of significant paradigmatic differences between the major banking systems of the world. The existing peculiarities in the mechanisms and methods of regulation of the banking sector within individual countries have caused drastic changes in views on the nature of the bank and its activities. The traditional view of banks as institutions of financial intermediation, providing the exchange of monetary assets between the owners of savings and borrowers, does not provide for the creation of new money. Instead, proponents of the alternative viewpoint emphasize that in today's world banks finance borrowers mainly through the mechanism of money emission. Both points of view are present to varying degrees in various theoretical and conceptual approaches to understanding the essence of the bank as an institution of financial intermediation. The current economic realities require a detailed study of national banking systems, which largely developed historically, and methodological aspects of their evolution in the context of global transformations. The research subject. In the process of evolution of theoretical and conceptual approaches to the definition of the essence of money, banks, the banking system, the prevailing point of view on this issue has not yet taken a definite form. Nevertheless, the recognition of the effectiveness of banks as a factor of economic growth brings together the positions of competing schools of economic theory. Banks become a factor in the investment process even in the theoretical models of the neoclassical school, which traditionally denies the dependence of economic growth on the money supply. Endogenous growth models recognize the role of banks primarily as a factor in accumulating capital and increasing savings, as well as a mediator between owners of savings and borrowers. Although the Keynesian school of thought initially gave little weight to the functioning of the banking system, neo-Keynesian models have attempted to explain the importance of confidence in the banking system and the need for sound regulatory constraints. The above-mentioned has urged us to carry out this research. The methodological framework of the research is based on an analysis of research on the global debate about the nature of banks in the economy and the architecture of monetary policy. A wide range of theoretical and empirical research methods were used: systematic analysis, synthesis and generalization to formulate conclusions. The aim of the research is to generalize and systematize the evolution of perspectives on money in the interpretations of today’s main economic schools. Conclusion. The findings consist of a conceptualization views' evolution on money, the banking sector in a more open economy to capital flows, and our firm belief that the banking system and the related process of money issuance affect income levels cyclically and over the long term.

Urban Brownfield Regeneration Projects: Complexities and Issues

Because of urban brownfields’ inherent complexity related to their very nature, as well as their intermediate scale—the neighbourhood—regeneration projects are not a spontaneous process. Indeed, an urban brownfield regeneration project may encounter several issues, which can be obstacles, barriers, or resistance, that we classify in four types: sociocultural barriers, governance involved by the multiplication of actors, legal and regulatory constraints, and deterrent costs. While these issues contribute in turn to complexify brownfield regeneration projects, they are not insurmountable. Finally, to overcome urban brownfield regeneration projects’ complexities and issues, we argue that there is a need to implement real project dynamics. To this end, we provide four potential approaches to foster the creative development of tailored solutions.