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We examine how short product life cycle lengths constrain real activities management among a group of manufacturing firms. Companies with short-cycle products face fast product obsolescence and constant pressure to develop and market new products. Fast product obsolescence increases the cost of overproduction, while constant pressure for new product development increases the cost of opportunistic spending cuts. We predict and find evidence that in general, short-cycle firms do not beat earnings thresholds through overproduction and discretionary spending cuts as extensively as long-cycle firms do. However, since the Sarbanes-Oxley Act came into effect, short-cycle firms have increasingly overproduced, and there is no longer a difference in overproduction between short- and long-cycle firms. Moreover, the presence of major customers attenuates the relationship between product life cycle lengths and real activities management, while a large market share and high fixed-assets intensity both accentuate the relationship. Finally, short-cycle firms are also less likely to use LIFO (last-in, first out) liquidation to inflate earnings than long-cycle firms. [ABSTRACT FROM AUTHOR]

Isoalantolactone (ISA) is a sesquiterpene lactone that could be isolated from Inula helenium as well as many other herbal plants belonging to Asteraceae. Over the past 2 decades, lots of researches have been made on ISA, which owns multiple pharmacological effects, such as antimicrobial, anticancer, anti-inflammatory, neuroprotective, antidepressant-like activity, as well as others. The anticancer effects of ISA involve proliferation inhibition, ROS overproduction, apoptosis induction and cell cycle arrest. Through inhibiting NF-κB signaling, ISA exerts its anti-inflammatory effects which are involved in the neuroprotection of ISA. This review hackled the reported pharmacological effects of ISA and associated mechanisms, providing an update on understanding its potential in drug development. [ABSTRACT FROM AUTHOR]

Poly-γ-glutamic acid (PGA) has been of interest as a sustainable biopolymer in industrial applications. PGA biosynthesis in Bacillus subtilis is catalyzed by a transmembrane protein complex comprising PgsB, PgsC, and PgsA. To determine the Pgs component responsible for PGA overproduction, we constructed recombinants in which the promoter of the host-derived pgs gene was replaced with another host-derived gene promoter. These recombinants were then transformed using high-copy-number plasmids with various pgs -gene combinations to enhance Pgs component in different ratios. Subsequently, PGA production was investigated in batch cultures with l -glutamate supplemented medium. The recombinant strain enhanced with pgsB alone significantly overproduced PGA (maximum production 35.8 g/L) than either the pgsC - or pgsA -enhanced strain. The molecular weight of the PGA produced with the pgsB -enhanced strain was also greater than that for the pgsC - or pgsA -enhanced strain (approximately 10-fold). Hence, PgsB enhancement alone contributes to PGA overproduction with increased molecular weight. [ABSTRACT FROM AUTHOR]

High fidelity DNA polymerase from Pyrococcus furiosus (Pfupol) is an attractive alternative to the highly popular DNA polymerase from Thermus aquaticus. Because this enzyme is in great demand for biotechnological applications, optimizing Pfupol production is essential to supplying the industry's expanding demand. T7-induced promoter expression in Escherichia coli expression systems is used to express recombinant Pfupol; however, this method is not cost-effective. Here, we have effectively developed an optimized process for the autoinduction approach of Pfupol expression in a defined medium. To better examine Pfupol's activities, its purified fraction was used. A 71 mg/L of pure Pfupol was effectively produced, resulting in a 2.6-fold increase in protein yield when glucose, glycerol, and lactose were added in a defined medium at concentrations of 0.05%, 1%, and 0.6%, respectively, and the condition for production in a 5 L bioreactor was as follow: 200 rpm, 3 vvm, and 10% inoculant. Furthermore, the protein exhibited 1445 U/mg of specific activity when synthesized in its active state. This work presents a high level of Pfupol production, which makes it an economically viable and practically useful approach. [ABSTRACT FROM AUTHOR]

Human monocarboxylate transporters (hMCTs) belong to the solute carrier 16 (SLC16) family of proteins and are responsible for the bi-directional transport of various metabolites, including monocarboxylates, hormones, and aromatic amino acids. Hence, the metabolic role of hMCTs is undisputable, as they are directly involved in providing nutrients for oxidation and gluconeogenesis as well as participate in circulation of iodothyronines. However, due to the difficulty in obtaining suitable amounts of stable hMCT samples, the structural information available for these transporters is limited, hindering the development of effective therapeutics. Here we provide a straightforward, cost-effective strategy for the overproduction of hMCTs using a whole-cell Saccharomyces cerevisiae-based system. Our results indicate that this platform is able to provide three hMCTs, i.e., hMCT1 and hMCT4 (monocarboxylate transporters), and hMCT10 (an aromatic amino acid transporter). hMCT1 and hMCT10 are recovered in the quantity and quality required for downstream structural and functional characterization. Overall, our findings demonstrate the suitability of this platform to deliver physiologically relevant membrane proteins for biophysical studies. [ABSTRACT FROM AUTHOR]

While previous panel studies have focused on the linear specifications of the industrial production-carbon emissions nexus, nonlinear panel studies on this relationship remain thin on the ground. This article examines the asymmetric nexus between industrial production and carbon emissions in 30 selected Sub-Saharan African countries spanning from 1990 to 2019. In the presence of cross-sectional dependence, the second-generation unit root tests were applied to examine the unit-root properties. The cointegration tests results confirm the presence of a long-run relationship among the variables. Finally, we employed the panel nonlinear autoregressive distributed lag approach to estimate the coefficient values. Generally, the empirical findings demonstrate that industrial production asymmetrically influences carbon emissions both in the short and long-runs. Specifically, the long-run estimates indicate that a positive shock in industrial production of 1% induces an increase in carbon emissions by 0.213%, while a negative shock induces a 0.390% decrease in carbon emissions. Based on these results, there is a need for policymakers in the selected Sub-Saharan African countries to consider the asymmetric behavior of industrial production while formulating industrialization policies. These policies should also be based on the condition of adopting green technology forms of energy. JEL Classification O14, Q5, Q54 [ABSTRACT FROM AUTHOR]

Ultraviolet B (UVB) irradiation causes photoaging, such as wrinkles, roughness and dryness of the skin, and it activates the production of reactive oxygen species (ROS) and inflammatory cytokines. In this study, the anti-photoaging activity of SEP-E (steam-exploded pine extract) was evaluated in HaCaT keratinocytes damaged by UVB irradiation. SEP-E treatment showed cytoprotective effects in HaCaT keratinocytes irradiated with UVB (40 mJ/cm²). SEP-E treatment reduced ROS overproduction and promoted the expression of antioxidant enzymes, such as catalase, superoxide dismutase 1, and superoxide dismutase 2. Additionally, SEPE treatment suppressed the expression of inflammatory cytokines, including interleukin 6, interleukin 8, and monocyte chemoattractant protein-1. Consequently, SEP-E shows potential as a natural material for photoaging treatment. [ABSTRACT FROM AUTHOR]

Monoterpene indole alkaloids (MIAs) are a group of plant-derived natural products with high-value medicinal properties. However, their availability for clinical application is limited due to challenges in plant extraction. Microbial production has emerged as a promising strategy to meet the clinical demands for MIAs. The biosynthetic pathway of cis-trans nepetalactol, which serves as the universal iridoid scaffold for all MIAs, has been successfully identified and reconstituted. However, bottlenecks and challenges remain to construct a high-yielding platform strain for cis-trans nepetalactol production, which is vital for subsequent MIAs biosynthesis. In the present study, we focused on engineering of Pichia pastoris cell factories to enhance the production of geraniol, 8-hydroxygeraniol, and cis-trans nepetalactol. By targeting the biosynthetic pathway from acetyl-CoA to geraniol in both peroxisomes and cytoplasm, we achieved comparable geraniol titers in both compartments. Through protein engineering, we found that either G8H or CPR truncation increased the production of 8-hydroxygeraniol, with a 47.8-fold and 14.0-fold increase in the peroxisomal and cytosolic pathway strain, respectively. Furthermore, through a combination of dynamical control of ERG20 , precursor and cofactor supply engineering, diploid engineering, and dual subcellular compartmentalization engineering, we achieved the highest ever reported production of cis-trans nepetalactol, with a titer of 4429.4 mg/L using fed-batch fermentation in a 5-L bioreactor. We anticipate our systematic metabolic engineering strategies to facilitate the development of P. pastoris cell factories for sustainable production of MIAs and other plant natural products. • Construction of geraniol-producing strains both in peroxisomes and cytoplasm. • Protein engineering increased 8-hydroxygeraniol titer by over 14- fold. • Dynamical regulation of ERG20 for enhanced production of monoterpenoids. • A platform for MIAs biosynthesis with the highest cis-trans nepetalactol titer. [ABSTRACT FROM AUTHOR]

Industrial revolutions have always brought about major changes in the life of mankind. The Fourth Industrial Revolution has revolutionized industrial production through digitalization, but has also had a major impact on service processes. However, the so-called Industry 4.0 technologies applied in the context of the fourth industrial revolution also allow new goals to be achieved that were not yet clearly defined in the paradigm of the fourth industrial revolution: sustainability, resiliency, and human-centricity. In this article, the author seeks to answer the questions of what existing technologies can be used to achieve the goals of sustainability, resiliency, and human-centricity, and what are the main research directions that can be used to develop a sustainable production and service environment. [ABSTRACT FROM AUTHOR]

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 μmol) and catechol (100 μmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery. [ABSTRACT FROM AUTHOR]

On October 18, 2019, Chile experienced the most important social upheaval since the country regained democracy in the late 1980s. The "Social Outbreak" surprised economic and political elites and seemed paradoxical to the international community who had often praised Chile as a model of successful development. In this paper, we used structural-demographic theory to analyze the interaction between the overproduction of elites and the stagnation in the relative income of the population as the underlying structural cause of Chilean political instability. This theory was able to predict the three most significant instances of political tension in the recent history of Chile: the crisis of the late 1960s that culminated in the coup d'état of 1973, popular mobilizations during the 1980s, and the recent student mobilizations and social upheaval. Our results suggest that, at least during the period 1938–2019, Chilean sociopolitical dynamics is determined by the same structural drivers. [ABSTRACT FROM AUTHOR]

Overproduction is one of the most significant wastes of Lean that can occur in any manufacturing company. Identifying and prioritizing failures that lead to overproduction are crucial tasks for operational managers and engineers. Therefore, this paper presents a new approach for determining the priority of failures that cause overproduction, based on an intuitionistic fuzzy Multi-Criteria Optimization model and the Failure Mode and Effects Analysis framework. The existing vagueness in the relative importance of risk factors and their values is described using natural language words, which are modeled with trapezoidal intuitionistic fuzzy numbers. Determining the relative importance of risk factors is defined as a fuzzy group decision-making problem, and the weight vector is obtained by applying the proposed Analytical Hierarchy Process with trapezoidal intuitionistic fuzzy numbers. The compromise solution, as well as the stability check of the obtained compromise solution, is achieved using the proposed Multi-Criteria Optimization and Compromise Solution with trapezoidal intuitionistic fuzzy numbers. The proposed model was applied to data collected from a process manufacturing company. [ABSTRACT FROM AUTHOR]

The commercial production of multifunctional, biocompatible, and biodegradable biopolymers such as poly‐γ‐glutamic acid via microbial fermentation requires the development of simple and cheap methods for mass production. This study optimized the poly‐γ‐glutamic acid production of Bacillus licheniformis ATCC 9945a in several steps. At first, the most critical components of the culture medium, including l‐glutamic acid, citric acid, and glycerol, were selected by screening nine factors through the Plackett–Burman experimental design and then were optimized using the response surface method and the central composite design algorithm. Under optimal conditions, the production of poly‐γ‐glutamic acid increased by more than 4.2 times from 11.2 to 47.2 g/L. This is one of the highest production rates of this strain in submerged batch fermentation reported so far using the optimized medium compared to the conventional base medium. A novel and efficient sudden pulse feeding strategy (achieved by a novel one‐factorial statistical technique) of l‐glutamic acid to the optimized medium increased biopolymer production from 47.2 to 66.1 g/L, the highest value reported in published literature with this strain. This simple, reproducible, and cheap fermentation process can considerably enhance the commercial applications of the poly‐γ‐glutamic acid synthesized by B. licheniformis ATCC 9945a. [ABSTRACT FROM AUTHOR]

In this study, a cost‐effective complex culture media containing molasses and corn steep liquor (CSL) was developed for the high production of bacterial cellulose (BC) by investigating the effect of four effective factors on BC production at three levels using Taguchi and combined methods. The predicted and actual values of BC production in optimal conditions by Taguchi and combined methods were 8.41 and 14.52 g/L, respectively. These results showed that the combined method was more suitable for predicting the optimal conditions in the optimization of BC production, the cost of developed culture medium was around 94% cost of HS medium preparation, molasses was the most effective factor in both experimental design methods, and initial pH adjustment had little impact on BC production. Then, the effect of inoculation conditions containing three factors of inoculation age, ethanol addition time, and agitation rate on the increase of BC production at three levels was investigated using the response surface methodology with the Box–Behnken design algorithm. Under the optimal conditions including inoculum age of 3 days, ethanol addition time of 10 days, and stirring speed of 100 rpm, the predicted and experimental results of BC production were 21.61 and 20.21 g/L, respectively. This is among the highest ever reported for BC production, which was achieved with a more cost‐effective culture medium containing molasses and CSL. [ABSTRACT FROM AUTHOR]

Sleep is an essential and evolutionarily conserved process that affects many biological functions that are also strongly regulated by cellular metabolism. The interdependence between sleep homeostasis and redox metabolism, in particular, is such that sleep deprivation causes redox metabolic imbalances in the form of over-production of ROS. Likewise (and vice versa), accumulation of ROS leads to greater sleep pressure. Thus, it is theorized that one of the functions of sleep is to act as the brain's "antioxidant" at night by clearing oxidation built up from daily stress of the active day phase. In this review, we will highlight evidence linking sleep homeostasis and regulation to redox metabolism by discussing (1) the bipartite role that sleep–wake neuropeptides and hormones have in redox metabolism through comparing cross-species cellular and molecular mechanisms, (2) the evolutionarily metabolic changes that accompanied the development of sleep loss in cavefish, and finally, (3) some of the challenges of uncovering the cellular mechanism underpinning how ROS accumulation builds sleep pressure and cellularly, how this pressure is cleared. [ABSTRACT FROM AUTHOR]

Although protein aggregation can cause cytotoxicity, such aggregates can also form to mitigate cytotoxicity from misfolded proteins, although the nature of these contrasting aggregates remains unclear. We previously found that overproduction (op) of a three green fluorescent protein-linked protein (3×GFP) induces giant aggregates and is detrimental to growth. Here, we investigated the mechanism of growth inhibition by 3×GFP-op using non-aggregative 3×MOX-op as a control in Saccharomyces cerevisiae. The 3×GFP aggregates were induced by misfolding, and 3×GFP-op had higher cytotoxicity than 3×MOX-op because it perturbed the ubiquitin-proteasome system. Static aggregates formed by 3×GFP-op dynamically trapped Hsp70 family proteins (Ssa1 and Ssa2 in yeast), causing the heat-shock response. Systematic analysis of mutants deficient in the protein quality control suggested that 3×GFP-op did not cause a critical Hsp70 depletion and aggregation functioned in the direction of mitigating toxicity. Artificial trapping of essential cell cycle regulators into 3×GFP aggregates caused abnormalities in the cell cycle. In conclusion, the formation of the giant 3×GFP aggregates itself is not cytotoxic, as it does not entrap and deplete essential proteins. Rather, it is productive, inducing the heat-shock response while preventing an overload to the degradation system. [ABSTRACT FROM AUTHOR]

Urbanization is a global phenomenon and is influenced by complex processes in the society. In Kazakhstan, the formation of towns was based on the implementation of a policy of the Russian Empire, which put in motion the processes of urbanization there. This policy was later continued in the Soviet times too. It began with the discovery of rich deposits of minerals on the sites of small Kazakh vernacular settlements, and their extraction. Gradually, these settlements turned into towns: infrastructure was built; population increased. Invariably, the living conditions of people engaged in industrial production also improved. However, at the end of the 20th century, these small towns are still experiencing a deep social and economic crisis. Although the modern independent Kazakhstan has begun to address them, this issue is still urgent. This paper examines the process of the formation of urban vernacular settlements in Kazakhstan with a case study of East Kazakhstan. The research employs archival documents containing objective information. It uses comparative historical analysis to identify the causes and reveal the processes of transformation of vernacular settlements into towns. It concludes that the emergence of some settlements in East Kazakhstan has been associated with the colonial policy of the Russian Empire. The towns are an important and inevitable part of urbanization. It is easier for the migrants and the villagers to adapt to the towns. This is because towns lack tensions and survival problems of the big cities, but retain all of their symbols and infrastructure. [ABSTRACT FROM AUTHOR]

Fusaric acid (FA), a picolinic acid derivative, is a natural substance produced by a wide variety of fungal plant pathogens belonging to the Fusarium genus. As a metabolite, fusaric acid exerts several biological activities including metal chelation, electrolyte leakage, repression of ATP synthesis, and direct toxicity on plants, animals and bacteria. Prior studies on the structure of fusaric acid revealed a co-crystal dimeric adduct between FA and 9,10-dehydrofusaric acid. During an ongoing search for signaling genes differentially regulating FA production in the fungal pathogen Fusarium oxysporum (Fo), we found that mutants lacking pheromone expression have an increased production of FA compared to the wild type strain. Noteworthy, crystallographic analysis of FA extracted from Fo culture supernatants showed that crystals are formed by a dimeric form of two FA molecules (1:1 molar stoichiometry). Overall, our results suggest that pheromone signaling in Fo is required to regulate the synthesis of fusaric acid. [ABSTRACT FROM AUTHOR]

We consider a bilateral monopoly where a linear input price is determined by Nash bargaining. We show, with an increasing marginal cost of input production, that vertical integration reduces consumer surplus and welfare compared with bilateral monopoly if the bargaining power of the input supplier is low. This result is important for competition policies as it questions the common wisdom suggesting vertical integration increases welfare by eliminating the problem of double marginalization. Overproduction under bilateral monopoly compared with vertical integration is the reason for our result. Interestingly, consumer surplus and welfare can be higher under a linear input price compared with a two‐part tariff input price. [ABSTRACT FROM AUTHOR]

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Copyright of Revista de Administración Pública is the property of Centro de Estudios Politicos y Constitucionales and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hyperpigmentation occurs due to irregular secretion of melanin pigment in the skin. This can affect quality of life depending on its severity, so prevention and management are essential. Oats (Avena sativa L.), a grain consumed worldwide, are known to offer improved health benefits upon germination and fermentation. This study is aimed to investigate the protective effects of lactobacilli-fermented sprouted oat extracts on oxidative stress and melanin overproduction in vitro. The anti-melanogenic effect was investigated using melanin content and tyrosinase activity assays in B16F10 cells, as well as a mushroom tyrosinase-based enzyme inhibition assay. The results showed that L. casei-fermented oat extracts were the most effective for reducing melanin formation by reducing the mRNA expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein 2. Furthermore, L. casei fermentation was effective in improving the total phenolic, flavonoid, and avenanthramide A contents of sprouted oat extracts. The results also demonstrated the antioxidant effects of L. casei-fermented sprouted oat extracts in promoting DPPH radical-scavenging activity, superoxide dismutase-like activity, and reduction in reactive oxygen species levels. Overall, the findings indicate that fermented sprouted oat extracts are promising candidates for antioxidant and anti-hyperpigmentation treatments. [ABSTRACT FROM AUTHOR]

Infections caused by Candida species, especially Candida albicans, threaten the public health and create economic burden. Shortage of antifungals and emergence of drug resistance call for new antifungal therapies while natural products were attractive sources for developing new drugs. In our study, fangchinoline, a bis‐benzylisoquinoline alkaloid from Chinese herb Stephania tetrandra S. Moore, exerted antifungal effects on planktonic growth of several Candida species including C. albicans, with MIC no more than 50 μg/mL. In addition, results from microscopic, MTT and XTT reduction assays showed that fangchinoline had inhibitory activities against the multiple virulence factors of C. albicans, such as adhesion, hyphal growth and biofilm formation. Furthermore, this compound could also suppress the metabolic activity of preformed C. albicans biofilms. PI staining, followed by confocal laser scanning microscope (CLSM) analysis showed that fangchinoline can elevate permeability of cell membrane. DCFH‐DA staining suggested its anti‐Candida mechanism also involved overproduction of intracellular ROS, which was further confirmed by N‐acetyl‐cysteine rescue tests. Moreover, fangchinoline showed synergy with three antifungal drugs (amphotericin B, fluconazole and caspofungin), further indicating its potential use in treating C. albicans infections. Therefore, these results indicated that fangchinoline could be a potential candidate for developing anti‐Candida therapies. [ABSTRACT FROM AUTHOR]

Most of the macro-literature on uncertainty has focused on macro-uncertainty caused by real activity as a source of economic fluctuations. Economic uncertainty reduces total demand in the economy via a conventional channel that is associated with real option theory. Given the findings of the existing literature, financial uncertainty other than macroeconomic uncertainty matters more for business cycle fluctuations. This study seeks to answer the following questions: Is uncertainty the primary cause of the business cycle's fluctuations? Alternatively, does it matter what kind of uncertainty exists? The research utilized the generalized linear model (GLM) and the Bayesian generalized linear model (BGLM) to analyze a dataset covering the time from July 1960 to April 2015 in the United States. Elevated levels of macroeconomic uncertainty, akin to real uncertainty, and economic policy uncertainty, as measured by news sources, demonstrate a counter-cyclical pattern in relation to business cycles. Low levels of uncertainty have a positive impact on business cycles, leading to an increase in industrial production. Conversely, high levels of uncertainty have a negative effect on business cycles, causing a decline in industrial output. We are of the opinion that high levels of macroeconomic uncertainty have a ripple effect on the entire economy, which may stifle investments, reduce consumption, and create unemployment, which is likely to influence labor participation. [ABSTRACT FROM AUTHOR]

This paper introduces a two-sector model of endogenous distributive cycles and overproduction, by using elements from Marxian and Kaleckian perspectives. The model combines the two-sector model with market power presented by Dutt (1988) with insights from the cyclical model of Goodwin (1967) and the model of growth and distribution of Dutt (1987). The paper establishes the analytical conditions for a short-run equilibrium point for sectoral capacity utilization rates. Furthermore, for the long run, considering capital accumulation, the paper demonstrates the existence of stable cycles in four dimensions (sectoral distribution of capital, employment rate, and markups for sectors producing capital and consumption goods). These findings are used to reinterpret overproduction within capitalist cycles, where the relative magnitudes of overaccumulation of capital and underconsumption change at different phases of the cycle, while full employment is not a relevant case. The paper concludes by suggesting insights for future research. [ABSTRACT FROM AUTHOR]

The pressure knapping technique develops circa 25,000 cal BP in Northeast Asia and excels at producing highly standardized microblades. Microblade pressure knapping spreads throughout most of Northeast Asia up to the Russian Arctic, and Alaska, in areas where the human presence was unknown. Swan Point CZ4b is the earliest uncontested evidence of human occupation of Alaska, at around 14,000 cal BP. It yields a pressure microblade component produced with the Yubetsu method, which is widespread in Northeast Asia during the Late Glacial period. Through the techno-functional analysis of 634 lithic pieces from this site, this study seeks to identify the techno-economical purposes for which the Yubetsu method was implemented. Data show that the microblade production system is related to an economy based on the planning of future needs, which is visible through blanks standardization, their overproduction, their functional versatility, and the segmentation of part of the chaîne opératoire. This expresses the efficiency and economic value of the microblade production system. The flexible use of pressure microblades identified at Swan Point CZ4b is also found in Japan, Korea, Kamchatka, and the North Baikal region, suggesting that their modes of use accompany the spread of early microblade pressure knapping over an immense territory across Beringia. [ABSTRACT FROM AUTHOR]

Cordycepin (COR) has attracted extensive attention for its medical value. Currently, separation and extraction from Cordyceps militaris is the main way to obtain COR, but it is time‐consuming and low efficiency. Heterologous synthesis of COR holds great promise for its industrial production. In this work, five COR synthases of different sources were obtained by homology screening, and were integrated into the genome of BY4741. Fermentation and determination of COR found that EA1 and EA2 from Emericellopsis atlantica were more suitable for COR synthesis. Then, ADO1 gene encoding adenosine kinase was knocked down, ADE4 gene encoding amidophosphoribosyltransferase and truncated cpdBN gene encoding 2′,3′‐cyclic‐nucleotide 2′‐phosphodiesterase/3′‐nucleotidase were overexpressed to enhance the accumulation of COR. Finally, the COR titer reached 725.16 mg L−1 in 5‐L bioreactor. This study lays a foundation for the heterologous synthesis and industrial production of COR, and also provides a reference for heterologous synthesis of other high value‐added chemicals. [ABSTRACT FROM AUTHOR]

The aim of this project is to verify the suitability of three-dimensional (3D) scanners with computer-aided systems as a new method of geometric feature inspection. Three-dimensional scanners are widely used for field recording and model reconstruction. However, at present, 3D scanning is rarely used in the field of inspection in the production process. This paper uses the Artec Leo 3D scanner as the basic equipment, randomly selects three different shapes of products for scanning, and then uses computer-aided software to optimize and feature the model. The analysis of the characteristics of the measurement data shows that the scanner has the potential to be used as an inspection tool in industrial production processes. [ABSTRACT FROM AUTHOR]

Hardware implementations of cryptographic primitives require protection against physical attacks and supply chain threats. This raises the question of secure composability of different attack countermeasures, i.e., whether protecting a circuit against one threat can make it more vulnerable against a different threat. In this article, we study the consequences of applying logic locking, a popular design-for-trust solution against intellectual property piracy and overproduction, to cryptographic circuits. We show that the ability to unlock the circuit incorrectly gives the adversary new powerful attack options. We introduce LEDFA (locking-enabled differential fault analysis) and demonstrate for several ciphers and families of locking schemes that fault attacks become possible (or consistently easier) for incorrectly unlocked circuits. In several cases, logic locking has made circuit implementations prone to classical algebraic attacks with no fault injection needed altogether. We refer to this "zero-fault" version of LEDFA by the term LEDA, investigate its success factors in-depth and propose a countermeasure to protect the logic-locked implementations against LEDA. We also perform test vector leakage assessment (TVLA) of incorrectly unlocked AES implementations to show the effects of logic locking regarding side-channel leakage. Our results indicate that logic locking is not safe to use in cryptographic circuits, making them less rather than more secure. [ABSTRACT FROM AUTHOR]

As China has emerged as a great economic power in the 21st century, comparativists and China scholars have sought to explore the characteristics of China's statist development model. Most accounts, however, have not taken seriously the policy implications of China's macroeconomic imbalance and its tendency to overproduction since the mid‐1990s. This article examines China's industrial‐policy‐centred responses to waves of overproduction crises from the late 1990s to the 2010s. China's expansive industrial policy incorporates demand‐side macroeconomic policy and long‐term planning for upgrading. This policy framework, designed to preserve the status quo, has been inherently lopsided, and has only served to reproduce China's macroeconomic imbalance. In the context of this persistent imbalance, China's industrial‐policy‐centred responses have contributed to periodic investment expansion of the state sector relative to the private sector, deepening ambitions around upgrading, and growing controversies regarding its statist model. In short, the statist features of China's economy have been periodically amplified by its particular responses to overproduction. This research shows that far from a statist shift engineered by President Xi Jinping, China's recent statist tendency has deeper historical and structural‐macroeconomic roots. This implies that the Chinese state adjusted and intensified its state interventions just as it underwent a profound process of marketization in the late 1990s. [ABSTRACT FROM AUTHOR]

Parental overproduction is hypothesized to hedge against uncertainty over food availability and stochastic death of offspring and to improve brood fitness. Understanding the evolution of overproduction requires quantifying its benefits to parents across a wide range of ecological conditions, which has rarely been done. Using a multiple hypotheses approach and 30 years of data, we evaluated the benefits of overproduction in the Blue-footed booby, a seabird that lays up to three eggs asynchronously, resulting in an aggressive brood hierarchy that facilitates the death of last-hatched chicks under low food abundance. Results support the resource-tracking hypothesis, as low prey abundance (estimated from sea surface temperature and chlorophyll-a concentration) led to rapid brood reduction. The insurance hypothesis was supported in broods of three, where last-hatched chicks' survival increased after a sibling's death. Conversely, in broods of two, results suggested that parents abandoned last-hatched chicks following first-hatched chicks' deaths. No direct evidence supported the facilitation hypothesis: the presence of a last-hatched chick during development did not enhance its sibling's fitness in the short or long term. The value of last-hatched offspring to parents, as "extra" or "insurance" varied with indices of food abundance, brood size, and parental age. Ninety percent of overproduction benefits came from enabling parents to capitalize on favorable conditions by fledging additional offspring. Our study provides insight into the forces driving overproduction, explaining the adaptiveness of this apparently wasteful behavior and allowing us to better predict how overproduction's benefits might be modified by ocean warming. [ABSTRACT FROM AUTHOR]

Human monocarboxylate transporters (hMCTs) belong to the solute carrier 16 (SLC16) family of proteins and are responsible for the bi-directional transport of various metabolites, including monocarboxylates, hormones, and aromatic amino acids. Hence, the metabolic role of hMCTs is undisputable, as they are directly involved in providing nutrients for oxidation and gluconeogenesis as well as participate in circulation of iodothyronines. However, due to the difficulty in obtaining suitable amounts of stable hMCT samples, the structural information available for these transporters is limited, hindering the development of effective therapeutics. Here we provide a straightforward, cost-effective strategy for the overproduction of hMCTs using a whole-cell Saccharomyces cerevisiae-based system. Our results indicate that this platform is able to provide three hMCTs, i.e., hMCT1 and hMCT4 (monocarboxylate transporters), and hMCT10 (an aromatic amino acid transporter). hMCT1 and hMCT10 are recovered in the quantity and quality required for downstream structural and functional characterization. Overall, our findings demonstrate the suitability of this platform to deliver physiologically relevant membrane proteins for biophysical studies.

The freshwater water flea (Daphnia magna Straus, 1820) is prey for numerous predators. Yet it possesses a wide range of strategies to defend itself against predation. The aim of this work is to investigate the defensive mechanisms employed by D. magna to reduce predation by the coelenterate Hydra viridissima, and two planarians, Polycelis felina and Dugesia gonocephala. To do this, we used a freshwater microcosm. An additional aim is to investigate interactions with the presence of the isolated endosymbiotic algae from green hydra, thus combining and observing the interaction of the zooplankton and microalgal component. Each experiment included five replicates (13.5 °C, 25 °C), in crystallizing glass containers (60 mL volume, 60 mm diameter, 35 mm height), including satiated (fed with larvae of Artemia salina) and starved predators, respectively (one or five individuals of a particular predator species in one microcosm). As the isolated microalgae are unique, we tracked the following three mechanisms of Daphnia defense for the first time including precisely this microalgal component: (i) grouping (visual magnification), i.e., two or more Daphnia holding together; (ii) the phenomenon of overproduction, i.e., any number of Daphnia in one container above the 10 initially added individuals; and (iii) accelerated movement ("bullet movement"), i.e., high-speed movements in particular microcosms. The results provide new information for a better understanding of the interspecific relationships in systems that include both zooplankton and microalgal components. [ABSTRACT FROM AUTHOR]

The study examines the development policy of the circular economy using the example of European Union countries based on the results of their circularity indicators. The respective countries fall into the "shift" country profile according to the distribution from the Global Circularity Gap, being consumers of the majority of global materials and generating 43% of emissions. Through the grouping of EU countries, it was found that high-circularity indicators do not necessarily determine a country's level of environmental friendliness. It has been identified that countries with high resource productivity levels (ranging from 5.8811 to 2.1397%), provided they have high and medium levels of product processing and investment in circular economy development, do not always have a positive impact on the environment. The corresponding research has led to the conclusion that the significant negative impact of the overproduction of goods and excessive resource consumption in European countries, which necessitates appropriate changes in societal activities. There is a need to adjust the policy directions of EU countries to stimulate their sustainable development in a closed-loop economy context, taking into account the specific characteristics and opportunities of each country, which will ensure a more effective adaptation to the implemented innovations. The results of this research can be applied to shaping the circular economy development policy and developing proposals for directions in societal development based on raising awareness about the consequences of interactions with the environment. [ABSTRACT FROM AUTHOR]

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Overproduction of desired native or nonnative biochemical(s) in (micro)organisms can be achieved through metabolic engineering. Appropriate rewiring of cell metabolism is performed by making rational changes such as insertion, up-/down-regulation and knockout of genes and consequently metabolic reactions. Finding appropriate targets (including proper sets of reactions to be knocked out) for metabolic engineering to design optimal production strains has been the goal of a number of computational algorithms. We developed FastKnock, an efficient next-generation algorithm for identifying all possible knockout strategies (with a predefined maximum number of reaction deletions) for the growth-coupled overproduction of biochemical(s) of interest. We achieve this by developing a special depth-first traversal algorithm that allows us to prune the search space significantly. This leads to a drastic reduction in execution time. We evaluate the performance of the FastKnock algorithm using various Escherichia coli genome-scale metabolic models in different conditions (minimal and rich mediums) for the overproduction of a number of desired metabolites. FastKnock efficiently prunes the search space to less than 0.2% for quadruple- and 0.02% for quintuple-reaction knockouts. Compared to the classic approaches such as OptKnock and the state-of-the-art techniques such as MCSEnumerator methods, FastKnock found many more beneficial and important practical solutions. The availability of all the solutions provides the opportunity to further characterize, rank and select the most appropriate intervention strategy based on any desired evaluation index. Our implementation of the FastKnock method in Python is publicly available at https://github.com/leilahsn/FastKnock. [ABSTRACT FROM AUTHOR]

Mucin overproduction is a common feature of chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), and exacerbates their underlying respiratory condition. Surfactant protein D (SP-D) protects against airway diseases through modulation of immune reactions, but whether it also exerts direct effects on airway epithelial cells has remained unclear. Therefore, we sought to investigate the inhibitory role of SP-D on mucin production in airway epithelial cells. We prepared air–liquid interface (ALI) cultures of human primary bronchial epithelial cells (HBECs), which recapitulated a well-differentiated human airway epithelium. Benzo(a)pyrene (BaP), a key toxicant in cigarette smoke, induced mucin 5AC (MUC5AC) production in ALI-cultured HBECs, airway secretory cell lines, and airway epithelia of mice. Then, the protective effects of SP-D against the BaP-induced mucin overproduction were examined. BaP increased MUC5AC production in ALI cultures of HBECs, and this effect was attenuated by SP-D. SP-D also suppressed the BaP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and MUC5AC expression in NCI-H292 goblet-like cells, but not in NCI-H441 club-like cells. Signal regulatory protein α (SIRPα) was found to be expressed in HBECs and NCI-H292 cells but absent in NCI-H441 cells. In NCI-H292 cells, SP-D activated SH2 domain-containing tyrosine phosphatase-1 (SHP-1), downstream of SIRPα, and knockdown of SIRPα abolished the suppressive effects of SP-D on BaP-induced ERK phosphorylation and MUC5AC production. Consistent with these in vitro findings, intratracheal instillation of SP-D prevented the BaP-induced phosphorylation of ERK and Muc5ac expression in airway epithelial cells in a mouse model. SP-D acts directly on airway epithelial cells to inhibit mucin secretion through ligation of SIRPα and SHP-1-mediated dephosphorylation of ERK. Targeting of SIRPα is therefore a potential new therapeutic approach to suppression of mucin hypersecretion in chronic airway diseases such as COPD and asthma. [ABSTRACT FROM AUTHOR]

The spatiotemporal dynamics of inflammation provide vital insights into the understanding of skin inflammation. Skin inflammation primarily depends on the regulatory feedback between pro- and anti-inflammatory mediators. Healthy skin exhibits fading erythema. In contrast, diseased skin exhibits expanding erythema with diverse patterns, which are clinically classified into five types: circular, annular, arcuate, gyrate, and polycyclic. Inflammatory diseases with expanding erythema are speculated to result from the overproduction of pro-inflammatory mediators. However, the mechanism by which feedback selectively drives the transition from a healthy fading erythema to each of the five types of diseased expanding erythema remains unclear. This study theoretically elucidates the imbalanced production between pro- and anti-inflammatory mediators and prospective treatment strategies for each expanding pattern. Our literature survey showed that eleven diseases exhibit some of the five expanding erythema, thereby suggesting a common spatiotemporal regulation underlying different patterns and diseases. Accordingly, a reaction-diffusion model incorporating mediator feedback reproduced the five observed types of diseased expanding and healthy fading patterns. Importantly, the fading pattern transitioned to the arcuate, gyrate, and polycyclic patterns when the productions of anti-inflammatory and pro-inflammatory mediators were lower and higher, respectively than in the healthy condition. Further depletion of anti-inflammatory mediators caused a circular pattern, whereas further overproduction of pro-inflammatory mediators caused an annular pattern. Mechanistically, the bistability due to stabilization of the diseased state exhibits circular and annular patterns, whereas the excitability exhibits the gyrate, polycyclic, arcuate, and fading patterns as the threshold of pro-inflammatory mediator concentration relative to the healthy state increases. These dynamic regulations of diffusive mediator feedback provide effective treatment strategies for mediator production wherein skins recover from each expanding pattern toward a fading pattern. Thus, these strategies can estimate disease severity and risk based on erythema patterns, paving the way for developing noninvasive and personalized treatments for inflammatory skin diseases. Author summary: The spatiotemporal dynamics of inflammation provide vital insights into understanding inflammation. Healthy skin exhibits fading inflammation, while diseased skin exhibits expanding inflammation with circular, annular, arcuate, gyrate, and polycyclic patterns. Diseases with expanding inflammation are thought to be linked to an overproduction of pro-inflammatory mediators, but how does the mediator production selectively transition from healthy fading inflammation to five diseased expanding inflammation? We used a mathematical model incorporating production and diffusion of mediators in the skin to simulate the fading and expanding patterns. The model reproduced the five observed types of diseased expanding and healthy fading patterns. We found that the fading pattern transitions in the order of arcuate, polycyclic, gyrate, annular, and circular patterns with increasing production of pro-inflammatory mediators or decreasing production of anti-inflammatory mediators. Importantly, dynamic feedback between pro-inflammatory and anti-inflammatory mediators is responsible for their production balance and controls health-to-disease transition of skin inflammation pattern. This mechanism guides treatment strategies and helps skin recover from expanding patterns towards a fading pattern. This research can help estimate disease severity and risk based on inflammation patterns and has potential applications in noninvasive and personalized treatments for inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

Mycotoxin deoxynivalenol (DON) produced by the Fusarium graminearum complex is highly toxic to animal and human health. During DON synthesis, the endoplasmic reticulum (ER) of F. graminearum is intensively reorganized, from thin reticular structure to thickened spherical and crescent structure, which was referred to as "DON toxisome". However, the underlying mechanism of how the ER is reorganized into toxisome remains unknown. In this study, we discovered that overproduction of ER-localized DON biosynthetic enzyme Tri4 or Tri1, or intrinsic ER-resident membrane proteins FgHmr1 and FgCnx was sufficient to induce toxisome-shaped structure (TSS) formation under non-toxin-inducing conditions. Moreover, heterologous overexpression of Tri1 and Tri4 proteins in non-DON-producing fungi F. oxysporum f. sp. lycopersici and F. fujikuroi also led to TSS formation. In addition, we found that the high osmolarity glycerol (HOG), but not the unfolded protein response (UPR) signaling pathway was involved in the assembly of ER into TSS. By using toxisome as a biomarker, we screened and identified a novel chemical which exhibited high inhibitory activity against toxisome formation and DON biosynthesis, and inhibited Fusarium growth species-specifically. Taken together, this study demonstrated that the essence of ER remodeling into toxisome structure is a response to the overproduction of ER-localized DON biosynthetic enzymes, providing a novel pathway for management of mycotoxin contamination. Author summary: The mycotoxin deoxynivalenol (DON) produced by the Fusarium graminearum complex is the most frequently detected mycotoxin in cereal grains worldwide. DON is synthesized in the compartmentalized organelle named "DON toxisome" that is highly remodeled, organized smooth endoplasmic reticulum (OSER). In this study, we demonstrated that ER remodeling into toxisome structure in F. graminearum is a response to overproduction of ER-localized DON biosynthetic enzymes, including Tri1 and Tri4. We further found that the HOG signaling pathway is important for the toxisome-shaped structure assembly. Moreover, using the Tri1-GFP labeled toxisome as a biomarker, we identified a novel small chemical exhibiting high inhibitory activity on toxisome assembly and DON biosynthesis. Our study elucidates the intrinsic mechanism of ER remodeling into toxisomes upon DON induction, and blocking the ER remodeling would provide a new avenue for management of FHB and mycotoxin contamination. [ABSTRACT FROM AUTHOR]

The human SLC7A10 transporter, also known as ASC-1, catalyzes the transport of some neutral amino acids. It is expressed in astrocytes, neurons, and adipose tissues, playing roles in learning, memory processes, and lipid metabolism, thus being involved in neurological and metabolic pathologies. Structure/function studies on this transporter are still in their infancy. In this study, we present a methodology for producing the recombinant human transporter in E. coli. Its transport function was assayed in proteoliposomes following the uptake of radiolabeled L-serine. After the testing of several growth conditions, the hASC-1 transporter was successfully expressed in BL21(DE3) codon plus RIL in the presence of 0.5% glucose and induced with 0.05 mM IPTG. After solubilization with C12E8 and cholesteryl hemisuccinate and purification by Ni-chelating chromatography, hASC-1 was reconstituted in proteoliposomes. In this experimental system it was able to catalyze an Na+-independent homologous antiport of L-serine. A Km for L-serine transport of 0.24 mM was measured. The experimental model developed in this work represents a reproducible system for the transport assay of hASC-1 in the absence of interferences. This tool will be useful to unveil unknown transport properties of hASC-1 and for testing ligands with possible application in human pharmacology. [ABSTRACT FROM AUTHOR]

An approach to obtain effective control of insertion loss (IL) in wideband substrate-integrated waveguide (SIW) band-pass filter with several tapered iris configurations is presented in this paper. Several iris configurations and iris parameters have been minutely studied and effective postulates have been provided for accurate design of filters with low IL throughout the transmission bandwidth. Basic structure is designed over a substrate with dielectric constant 3.2 and material thickness of 30 mils. The structures are then successfully modified into a band-pass filter with its pass band in Ku bands with minimal IL using waveguide iris method. The technique effectively serves the purpose to achieve greater control over the IL and isolation. Maximum IL of 2 dB is reduced by 1.5 dB and close to 0.5 dB IL is obtained in the final configuration using the tapering technique. Proposed techniques are supported with theoretical explanations. All designs are fabricated, and measured results are found to validate the concept produced in this paper. The study provides a direct solution to the SIW Iris filter design engineers considering all major parameters necessary for industrial/scientific productions. [ABSTRACT FROM AUTHOR]

Surfactants are used in many industries such as agriculture, petrochemicals, and bioremediation. Developing using greener products leads to garnering more attention to biosurfactants. The advantages of biosurfactants compared with chemical surfactants are proper biodegradability, less toxicity, environmentally friendly, and higher efficiency. However, high production costs and low yields are important problems in the economic production of biosurfactants. As a result, optimizing and increasing the production of biosurfactants are of great importance. In this study, continuous chemostat fermentation was used to raise process time, control the process parameters, and increase the efficiency of rhamnolipid biosurfactant by Pseudomonas aeruginosa HK02. First, the best carbon source, the concentration of the minerals in the feed, and the process parameters were determined. Then, experiments were done at different flow rates to determine the washout and optimal flow rate with high yield. The best source of carbon for this strain was sunflower and soybean oil. KS 6.63 (g/L) and μmax 0.0377 (1/h) were obtained. The flow rate of 240 mL/day with a yield(p/s) of 0.88 (g/g) had the highest efficiency. The process was tested at a flow rate of 240 mL/day for 30 days. The washout flow rate was 600 mL/day. The biosurfactant production reaches 200 g/L at optimum condition. The produced biosurfactant was able to reduce the surface tension of water to 31 mN/m at 450 ppm. The results showed that the continuous fermentation process was more economical and suitable for large-scale production of rhamnolipid biosurfactants, because of high productivity, and the possibility of continuing the process for one month and more. [ABSTRACT FROM AUTHOR]

Deferred income taxation is widely used to encourage investment or saving. However, most income tax bases are more or less distortive (non-neutral). Using lab experiments, we find that the deferral of a distortive income taxation can result in substantial overproduction and less willingness to take risks. Subjects underweight the deferred tax burden and neglect the tax distortion because they act myopically and tend to make choices in isolation rather than simultaneously (choice bracketing). Despite opportunities to learn, the overproduction remains substantial. Additional analyses confirm that the observed misperception of deferred taxes is not caused by low tax salience or low effort, as providing additional accounting information on deferred taxes and introducing accountability reports do not change overproduction behavior. Only if we change the timing of the taxation from deferred to an economically equivalent immediate distortive tax system do overproduction and the effect on asset allocation almost disappear. [ABSTRACT FROM AUTHOR]

Prior research finds that firms with patterns of consecutive earnings increases are rewarded by market participants with higher Price-Earnings (P/E) multiples, and that some firms manage earnings to sustain the earnings stream. We propose several fast and inexpensive heuristics to classify firms as suspect or non-suspect of maintaining the stream through earnings management and examine whether market rewards differ for suspect and non-suspect firms. We find higher P/E multiples for firms with a pattern of increasing earnings supported by the same pattern of increasing cash flows (non-suspect). This is an important result as it shows that cash flows can be used to assess the quality of earnings in scenarios prone to earnings management, where earnings quality is expected to be low. We also find lower price-earnings multiples for firms suspected of using accrual-based earnings management, sales manipulation, and overproduction to achieve the earnings pattern. [ABSTRACT FROM AUTHOR]

We start with two main hypotheses: a) the tendency to overproduction and expanded reproduction is inevitable in a context of production based on competition and the search for profit; b) conflicts for resources and the tendential degradation of the quality of life are also inevitable and are only going to worsen as the expanded reproduction takes its toll on the environment and on the material conditions for the reproduction of capital. This paper explores some underlying phenomena to support these claims, such as the Jevons Paradox, the Tendency of the Rate of Profit to Fall, and the Energy Return on Investment. Finally, it discusses the failure of some of the alternatives to the Growth Paradigm: Sustainable Development, Green Growth, Circular Economy and Degrowth.

Mannan and outer structural yeast cell wall polysaccharides have recently garnered attention for their health defense and cosmetic applications. In addition, many studies have confirmed that yeast cell wall mannans exhibit various biological activities, such as antioxidant, immune regulation, reducing hyperlipidemia, and gut health promotion. This paper elucidates yeast cell wall mannan structural features, biological activities, underlying molecular mechanisms, and biosynthesis. Moreover, mannan-overproducing strategies through yeast strain engineering are emphasized and discussed. This review will provide a scientific basis for yeast cell wall mannan research and industrial applications.