Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.

In this paper, we will revisit the derivation of Heisenberg's uncertainty principle. We will see how the Heisenberg principle collapses at the Planck scale by introducing a minor modification. The beauty of our suggested modification is that it does not change the main equations in quantum mechanics; it only gives them a Planck scale limit where uncertainty collapses. We suspect that Einstein could have been right after all, when he stated, ``God does not throw dice." His now-famous saying was an expression of his skepticism towards the concept that quantum randomness could be the ruling force, even at the deepest levels of reality. Here we will explore the quantum realm with a fresh perspective, by re-deriving the Heisenberg principle in relation to the Planck scale. We will show how this idea also leads to an upper boundary on uncertainty, in addition to the lower boundary. These upper and lower boundaries are identical for the Planck mass particle; in fact, they are zero, and this highlights the truly unique nature of the Planck mass particle. Further, there may be a close connection between light and the Planck mass particle: In our model, the standard relativistic energy momentum relation also seems to apply to light, while in modern physics light generally stands outside the standard relativistic momentum energy relation. We will also suggest a new way to look at elementary particles, where mass and time are closely related, consistent with some of the recent work in experimental physics. Our model leads to a new time operator that does not appear to be in conflict with the Pauli objection. This indicates that both mass and momentum come in quanta, which are perfectly correlated to an internal Compton `clock' frequency in elementary particles.

What is the function of cognition? On one influential account, cognition evolved to co-ordinate behaviour with environmental change or complexity (Godfrey-Smith 1996). Liberal interpretations of this view ascribe cognition to an extraordinarily broad set of biological systems – even bacteria, which modulate their activity in response to salient external cues, would seem to qualify as cognitive agents. However, equating cognition with adaptive flexibility per se glosses over important distinctions in the way biological organisms deal with environmental complexity. Drawing on contemporary advances in theoretical biology and computational neuroscience, we cash these distinctions out in terms of different kinds of generative models, and the representational and uncertainty-resolving capacities they afford. This analysis leads us to propose a formal criterion for delineating cognition from other, more pervasive forms of adaptive plasticity. On this view, biological cognition is rooted in a particular kind of functional organisation; namely, that which enables the agent to detach from the present and engage in counterfactual (active) inference.

Understanding tourist behaviour during and after major tourism crises is essential to help destinations recover. The COVID-19 pandemic, a period of uncertainty and risk, makes it relevant to assess factors that influence travel intentions. There has been little research on tourist behaviour during health crises and, in particular, on perceived health risk and uncertainty effects on travel intentions. This study was carried out during the first months of the pandemic in Brazil and aims to investigate the role of health risk perception and intolerance of uncertainty on travel intentions for 2020 and 2021. We applied an online survey to 1,150 Brazilian participants from March to May of 2020. Our findings indicate that perceived COVID-19 severity, perceived probability of contracting it, and expected pandemic duration are significant predictors of travel intentions for both years. This paper sheds new light on tourist behaviour in the context of global health crises.

The aim of this study was to develop, implement, and evaluate a new auxiliary enterprise risk management framework and process to serve as an enabler to the global ISO 31000 risk framework and ISO 31010 processes. This framework has been designed particularly for use within high-risk environments and those characterized by volatility, uncertainty, complexity, and ambiguity (VUCA). This paper proposes a methodology for optimization of structured sharing and grass-roots management of all available risk-sentience information with the assessed potential to develop into an identifiable risk in the future. The author introduces new risk terminology including risk-sentience, risk-sentience information, and risk-sentience management. The process involved the development of the Theory of Risk-Sentience (ToRS), Risk-Sentience Auxiliary Framework (RSAF) and a risk-sentience management process referred to as LUOMEAR (Learning from Uncertainties, Others Mistakes, Experiences and Anecdotal Reporting). Manchester Patient Safety Framework (MaPSaF), SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis, and a newly developed Risk-Sentience Fertility Checklist were used to conduct pre and post-trial evaluations. The findings include positive adjustments in safety culture, components of commitment to quality, communication and team-working around safety issues, access to evolving risk-information, and efficient sharing and management of recorded risk-information. Recommendations are made for more extensive application of both the proposed auxiliary risk framework and process within high-risk sectors to further explore its effectiveness and scope.

Visualizing geo-spatial data embedded into a three-dimensional terrain is challenging. The problem becomes even more complex when uncertainty information needs to be presented as well. This paper addresses the question of how to visually communicate all three aspects: the 3D terrain, the geo-spatial data, and the data-associated uncertainty. We argue that visualizing all aspects with a high degree of detail will likely exceed the visual budget. Therefore, we propose a visualization strategy based on prioritizing a selected aspect and presenting the remaining two with less detail. We discuss various design options that allow us to obtain differently prioritized visual representations. Our approach has been implemented as a tool for rapid visualization prototyping in the context of avionics applications. Practical solutions are described for a use case related to the visualization of 3D terrain and uncertain weather data.

Ectopic expression of the MYB transcription factor of AmROSEA1 from Antirrhinum majus has been reported to change anthocyanin and other metabolites in several species. In this study, we found that overexpression of AmRosea1 significantly improved the tolerance of transgenic rice to drought and salinity stress. Transcriptome analysis revealed that a considerable amount of stress-related genes were affected by exogenous AmRosea1 during both drought and salinity stress treatments. These affected genes are involved in stress signal transduction, the hormone signal pathway, ion homeostasis and the enzymes that remove peroxides. This work suggests that the AmRosea1 gene is a potential candidate for genetic engineering of crops.

Supervised land-use/land-cover (LULC) classifications are typically conducted using class assignment rules derived from a set of multiclass training samples. Consequently, classification accuracy varies with the training data set and is thus associated with uncertainty. In this study, we propose a bootstrap resampling and reclassification approach that can be applied for assessing not only the uncertainty in classification results of the bootstrap-training data sets, but also the classification uncertainty of individual pixels in the study area. Two measures of pixel-specific classification uncertainty, namely the maximum class probability and Shannon entropy, were derived from the class probability vector of individual pixels and used for the identification of unclassified pixels. Unclassified pixels that are identified using the traditional chi-square threshold technique represent outliers of individual LULC classes, but they are not necessarily associated with higher classification uncertainty. By contrast, unclassified pixels identified using the equal-likelihood technique are associated with higher classification uncertainty and they mostly occur on or near the borders of different land-cover.

The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

Errors during manufacture of high value components are not acceptable nowadays in driving industries such as energy and transportation. Sectors such as aerospace, automotive, shipbuilding, nuclear power, large science facilities or wind power manufacture complex and accurate components that demand close measurements and fast feedback into manufacturing processes. New measuring technologies are already available in machine tools, including integrated touch probes and fast interface capabilities. They shall provide the possibility to measure the workpiece during or after the manufacturing process, maintaining the original setup of the workpiece and avoiding the manufacturing process from being interrupted to transport the workpiece to a measuring position. However, the traceability of the measurement process on a machine tool is not ensured yet and measurement data is still not fully reliable for process control or product validation. Due to the similarity between a coordinate measuring machine and a machine tool, some of the methods applied for a correct assessment of uncertainty in coordinate measuring machines are adapted to the challenges of a machine tool. The scientific objective is to determine the uncertainty on a machine tool measurement and, in this way, convert it into a machine integrated traceable measuring process. This paper reviews the fundamentals of machine tool metrology.

A simple method for the determination of caffeine in coffee grains by GC-FID is presented in the current work. The method was fully validated according to ISO 17025 requirements and European Commission regulation. The accuracy, as provided by recovery experiments was higher than 93%, and the precision, as provided by the (%)Relative standard deviation under reproducibility conditions, was lower than 5%. All independent parameters that lead in the increase of methods uncertainty were investigated. In the present work all special precautions were taken into account in order to avoid the use of an internal standard. The method was applied in real samples and possible health claims were investigated.

Statistical modeling lies at the heart of product design and development throughout numerous engineering disciplines, especially since processing large amounts of data has become increasingly ubiquitous. While mathematical statistics provide elegant guidance pertaining to the question of whether or not some particular underlying modeling assumptions are justified and appropriate, when pursuing a more comprehensive assessment of product design and development other considerations often increase in significance. Therefore, we will examine and analyze the tedious interactions and implications of statistical modeling choices and product liability exposure. To the best of our knowledge, this paper is the first to draw attention to and explore some often overlooked or oversimplified dangers and pitfalls that enter the equation when product design heavily relies on statistical modeling. In particular, through a diligent analysis of both statistical and legal aspects we will explore how statistically optimal procedures may yield far from optimal outcomes in terms of product liability when applied to actual real life problems and why suboptimal nonparametric or robust approaches may constitute better alternatives.

Knowledge-based approaches are useful alternatives to predict the Failure Probability (FP) coping with the insufficient data, process integrity, and complexity issue in manufacturing systems. This study proposes a Fault Tree Analysis (FTA) approach as proactive knowledge-based technique to estimate the FP based maintenance planning with subjective information from domain experts. However, the classical-FTA still suffers from uncertainty and static structure limitations which poses a substantial dilemma in predicting FP. To deal with the uncertainty issues, a Fuzzy-FTA (FFTA) model was developed by statistical analysing the effective attributes such as experts' trait impacts, scales variation and, assorted membership and defuzzification functions. Besides, a Bayesian Network (BN) theory was conducted to overcome the static limitation of classical-FTA. The results of FFTA model revealed that the changes in decision attributes were not statistically significant on FP variation while BN model considering conditional rules to reflect the dynamic relationship between events had more impact on predicting FP. After all, the integrated FFTA-BN model was used in the optimization model to find the optimal maintenance intervals according to estimated FP and the total expected cost. As a practical example, the proposed model was implemented in a semi-automatic filling system in an automotive production line. The outcomes could be useful for upgrading the availability and safety of complex equipment in manufacturing systems.

In this paper, we relate Poisson’s summation formula to Heisenberg’s uncertainty principle. They both express Fourier dualities within the space of tempered distributions and these dualities are furthermore the inverses of one another. While Poisson’s summation formula expresses a duality between discretization and periodization, Heisenberg’s uncertainty principle expresses a duality between regularization and localization. We define regularization and localization on generalized functions and show that the Fourier transform of regular functions are local functions and, vice versa, the Fourier transform of local functions are regular functions.

NASA mission systems proposals are often compared using an equivalent system mass (ESM) framework wherein all elements of technology to deliver an effect- its components, operations and logistics of delivery- are converted to effective masses since this has a known cost scale in space operations. To date, ESM methods and the tools for system comparison have not considered complexities wherein systems that serve a mission span multiple transit and operations stages, such as would be required to support a crewed mission to Mars, and thus do not account for the different mass equivalency factors operational during each period and the inter-dependencies of the costs across the mission. Further, ESM does not account well for the differential reliabilities of the underlying technologies. Less reliability should incur an equivalent mass cost for technologies that might otherwise provide a mass advantage. We introduce an extensions to ESM to address these limitations and show that it provides a direct method for analyzing, optimizing and comparing different mission systems. We demonstrate our extended ESM (xESM) calculation with crop production technologies -- an aspect of the developing offworld biomanufacturing suite -- since it represents a case with strong coupling among stages of the mission and a relatively high-risk profile.

The aim of this article is to propose a core game theory model of transaction costs wherein it is indicated how direct costs determine the probability of loss and subsequent transaction costs. The existence of optimum is proven, and the way in which exposure influences the location of the optimum is demonstrated. The decisions are described as a two-player game and it is discussed how the transaction cost sharing rule determines whether the optimum point of transaction costs is the same as the equilibrium of the game. The dispute between actors regarding changing the share of transaction costs to be paid by each party is modeled by a non-cooperative bargaining game. Requirements of efficient transaction cost sharing rules are defined, and it is posited that solution exists which is not unique. Policy conclusions are also devised based on principles of design of institutions to influence the nature of transaction costs.

We have recently presented a unified quantum gravity theory [1]. Here we extend on that work and present an even simpler version of that theory. For about hundred years, modern physics has not been able to build a bridge between quantum mechanics and gravity. However, a solution may be found here; we present our quantum gravity theory, which is rooted in indivisible particles where matter and gravity are related to collisions and can be described by collision space-time. In this paper, we also show that we can formulate a quantum wave equation rooted in collision space-time, which is equivalent to mass and energy.The beauty of our theory is that most of the main equations that currently exist in physics are not changed (in terms of predictions), except at the Planck scale. The Planck scale is directly linked to gravity and gravity is, surprisingly, actually a Lorentz symmetry as well as a form of Heisenberg uncertainty break down at the Planck scale. Our theory gives a dramatic simplification of many physics formulas without altering the output predictions. The relativistic wave equation, the relativistic energy momentum relation, and Minkowski space can all be represented by simpler equations when we understand mass at a deeper level. This not attained at a cost, but rather a reflection of the benefit in having gravity and electromagnetism unified under the same theory.

Coastal inundation is an increasing problem. Sea-level rise will greatly increase the frequency and depth of inundation, forcing vulnerable communities to adapt. Communities will need to decide when and how to adapt. The process of decision-making along adaptive pathways is now being used internationally to plan for adaptation over time by anticipating decision points in the future however it unfolds. This process requires risk and uncertainty considerations to be transparent in the scenarios used in such planning. We outline a framework for uncertainty identification and management within coastal hazard assessments which recognizes different types of decision and identifies the types of uncertainty that must be accounted for, such as statistical, scenario and deep uncertainty types. We show how coastal-inundation hazard can be mapped and presented in a way that clearly separates sources of uncertainty, so that they are transparent within a dynamic adaptive pathways planning process. Traditional coastal inundation maps show inundated area only. We present maps of inundation depth and frequency which clearly show the degree of exposure, where that exposure occurs, and how much sea-level rise can be tolerated. The new uncertainty framework and mapping techniques can better identify decision points and their expected time range, which provides more useful input to the adaptation process than traditional coastal inundation assessments.

Salinity is a known factor which shapes population dynamics and community structure through direct and indirect effects towards aquatic ecosystems. The responses of Moina macrocopa (Cladocera) collected from Setiu Wetland lagoon (Terengganu) were evaluated through manipulative laboratory experiments to understand the ability of M. macrocopa to tolerate under high salinity stress. Specifically, the fatty acid composition, growth, survival and reproduction of this cladocerans species were examined. Sodium chloride (NaCl) were used in the treatments water with the concentration 0, 4, 6, 8, 12, and 15psu. Fatty acid levels were determined using Gas Chromatography and Mass Spectrophotometry (GC-MS). Results clearly indicate that normal conditions give the highest content of fatty acid, especially the polyunsaturated fatty acid content like EPA (eicosapentaenoic acid), ALA (alpha-linoleic acid), ARA (arachidonic acid) and DHA (docosahexaenoic acid). Furthermore, M. macrocopa survival also was best at 0psu, with percentage reached 98%, whereas the opposite occurred at 15psu, with approximately 9% of viable animals survived. On other aspects, M. macrocopa also showed the highest reproduction rate at 0psu (e.g. average initial age of reproduction, 4.33±0.58 days) compared with other salinities level. Interestingly, the difference in terms of growth at different salinities was unapparent, an unexpected outcome when adverse effects such as osmoregulation pressure on the organism are considered. Based on the results, we conclude that M. macrocopa can only tolerate salinity below 8psu and, is unable to withstand stressful environmental condition engendered with salinities above 8psu.

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Multi-criteria decision analysis (MCDA), one of the prevalent branches of operations research, aims to design mathematical and computational tools for selecting the best alternative among several choices with respect to specific criteria. In the cloud, MCDA based online brokers uses customer specified criteria to rank different service providers. However, subjected to limited domain knowledge, the customer may exclude relevant or include irrelevant criterion, which could result in suboptimal ranking of service providers. To deal with such misspecification, this research proposes a model, which uses notion of factor analysis from the domain of unsupervised machine learning. The model is evaluated using two quality-of-service (QoS) based datasets. The first dataset i.e., feedback from customers, was compiled using leading review websites such as Cloud Hosting Reviews, Best Cloud Computing Providers, and Cloud Storage Reviews and Ratings. The second dataset i.e., feedback from servers, was generated from cloud brokerage architecture that was emulated using high performance computing (HPC) cluster at University of Luxembourg (HPC @ Uni.lu). The simulation runs in a stable cloud environment i.e. when uncertainty is low, shows that online broker (equipped with the proposed model) produces optimized ranking of service providers as compared to other brokers. This is due the fact that proposed model assigns priorities to criteria objectively (using machine learning) rather than using priorities based on subjective judgments of the customer. This research will benefit potential cloud customers that view insufficient domain knowledge as a limiting factor for acquisition of web services in the cloud.

Contrary to the long-held belief that the effects of vaccines are specific for the disease they were created; compelling evidence has demonstrated that vaccines can exert positive or deleterious non-specific effects (NSEs). In this review, we compiled research reports from the last 40 years, showing that live vaccines induce positive NSEs, whereas non-live vaccines induce several negative NSEs, including increased female mortality associated with enhanced susceptibility to other infectious diseases, especially in developing countries. These negative NSEs are determined by the vaccination sequence, the antigen concentration in vaccines, the type of vaccine used (live vs. non-live), and also by repeated vaccination. We do not recommend stopping using non-live vaccines, as they have demonstrated to protect against their target disease, so the suggestion is that their detrimental NSEs can be minimized simply by changing the current vaccination sequence. High IgG4 antibody levels generated in response to repeated inoculation with mRNA COVID-19 vaccines could be associated with a higher mortality rate from unrelated diseases and infections by suppressing the immune system. Since most COVID-19 vaccinated countries are reporting high percentages of excess mortality not directly attributable to deaths from such disease, the NSEs of mRNA vaccines on overall mortality should be studied in depth.

The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor throughout the globe. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing ’omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A. mellifera. By highlighting the most promising traits of varroa-surviving bees and our current knowledge on their genetic bases, this work will help direct future research efforts and selection programs to control this pest. Additionally, by comparing the diverse populations of honey bees that exhibit the traits, this review highlights the consequences of anthropogenic and natural selection on the interactions between hosts and parasites.

The burdens of malnutrition, protein and micronutrient deficiency, and obesity cause enormous costs to society. Crop nutritional quality has been compromised by the emphasis on edible yield and through the loss of biodiversity due to the introduction of high-yielding uniform cultivars. Heirloom crop cultivars are traditional cultivars grown for a long time (> 50 years), and whose heritage has been preserved by regional, ethnic or family groups. Heirlooms are recognized for their unique appearance, names, uses and historical significance. They are gaining in popularity because of their unique flavors and cultural significance to local cuisine, and their role in sustainable food production for small-scale farmers. As a contrast to modern cultivars, heirlooms may offer a welcome alternative in certain markets. Recently, market channels have emerged for heirloom cultivars in the form of farmer-breeder-chef collaborations and seed savers organizations. There is therefore urgent need to know more about the traits available in heirloom cultivars, particularly for productivity, stress tolerance, proximate composition, sensory quality and flavor. This information is scattered and the intention of this review is to document some of the unique characteristics of heirloom cultivars that may be channeled into breeding programs for developing locally adapted high value cultivars.

This paper investigates how Islamic tolerance contributes to solve religious conflict today that has impacted on various aspects such as economic collapse, insecurity in life, lack of professional society, academic retrogressions, and so on. Knowledge of these issues has become an urgent to build a community that is full of peace, harmony and unity. The paper suggests that Quranic views on tolerance should be understood and practiced in order to avoid disunity in society which is due to failure to appreciate tolerance values in association. The paper concludes problems or misunderstandings always occur in different religious societies, since every religion has its own teachings and principles, as well as each of them is interpreted in different ways.

According to the current understanding, the recently observed accelerated expansion of the universe is caused by the dark or the vacuum energy. Attempts to calculate the magnitude of this energy using the standard model of particle physics led to values which are 59 – 120 orders of magnitude larger than the experimentally estimated one. Even though the expanding space has positive internal energy, in a flat universe it is completely balanced by the negative energy of gravitational field making the net energy equal to zero. However, the current physical theories may breakdown for times less than or on the order of Planck time and one cannot assume that the above assertion concerning the balance of two energies is valid also in this time scale. In this note it is assumed that this balance of the two energies during the creation of new space as the universe expands takes place only for times larger than the Planck time. If this assumption is correct, the net energy of the newly created space remains positive for times on the order of Planck time and the positive vacuum energy has to be burrowed from empty space before it is being balanced by gravity. This can happen only within the restrictions of the time-energy uncertainty principle. In this note it is shown that such considerations lead to a vacuum energy density of about 0.3 Nanojoules per cubic meter which has to be compared with the measured value of 0.6 Nanojoules per cubic meter.

Hydro-climatic projections in West Africa are attributed with high uncertainties that are difficult to quantify. This study assesses the influence of the parameter sensitivities and uncertainties of three rainfall runoff models on simulated discharge in current and future times using meteorological data from 8 Global Climate Models. The IHACRES Catchment Moisture Deficit (IHACRES-CMD) model, the GR4J and the Sacramento model were chosen for this study. During model evaluation, 10,000 parameter sets have been generated for each model and used in a sensitivity and uncertainty analysis using the Generalized Likelihood Uncertainty Estimation (GLUE) method. Out of the three models, IHACRES-CMD recorded the highest Nash-Sutcliffe Efficiency (NSE) of 0.92 and 0.86 for the calibration (1997-2003) and the validation (2004-2010) period respectively. The Sacramento model was able to adequately predict low flow patterns on the catchment while the GR4J and IHACRES-CMD over and under estimate low flow respectively. The use of multiple hydrological models to reduce uncertainties caused by model approaches is recommended along with other methods of sustainable river basin managements.

Farmers and seed companies constantly require high-quality seeds with excellent agronomic performance. However, faced with environmental adversity, limited natural resources and increasing food demand around the globe, more attention has turned to improving crop plant production by implementing efficient strategies. Seed priming technology has shown promising biological improvements leading to suitable agronomic performance in crop plants under adverse environmental conditions. Seeds are subjected to controlled conditions that are conducive to complex physiological, biochemical, and molecular changes, conferring specific stress tolerance to subsequent germination and growth conditions. In this review paper, we aimed to study the recent approaches in the efficiency of hydropriming, osmopriming, chemopriming, hormopriming, nanopriming, matrix priming, biopriming, physical priming and hybrid priming procedures in the production of crop plants under environmental adversity, as well as their biological mechanism changes. All priming methods demonstrated relevant changes in the biological mechanism related to crop plant production by mitigating salinity effects, heavy metals, and flooding stress and enhancing chilling, heat, drought and phytopathogen tolerance. We strongly recommend that researchers combine multiple priming methods, known as hybrid priming, in their investigations to provide novel technologies and additional biological approaches to enhance the knowledge of crop plant science. Thus, the findings shed light on the use of seed priming technology as a key strategy to increase crop plant production under environmental adversity by acquiring stress tolerance and enhancing agronomic traits to meet the global food demand.

Is it true that the nuclear technology applied to electric energy generation offers a clean, safe, reliable and affordable i.e. sustainable alternative? Yes it is, but its impact on the environment strongly depends on the implementation bearing residual risks due to a human factor, technical failures or natural catastrophes. A full response is therefore difficult and can first be given when the wicked multi-disciplinary problems get well formulated and “solved”. These problems have multi-dimensional nature lying at the interface between: necessary R&D effort, the industrial deployment and the technology impact in view of the environmental sustainability including the management of produced hazardous waste. This enormous complexity indicates that just a description of the problem might represent a problem. The paper proposes a holistic approach to assess the nuclear energy systems potential with respect to sustainable performance applying Multi-criteria decision analysis with a suitable objective tree and a multi-level criteria structure and examines the trading-off techniques for ranking of the alternatives. The framework proposes a multi-criteria and multi-stakeholders treatment which can be used as a pre-decisional support towards an implementation of nuclear fuel cycles adapted to national preferences and priorities. Proposed approach addresses some aspects of the environmental footprint of nuclear energy systems. Advanced nuclear fuel cycles, previously investigated by the NEA/OECD expert group WASTEMAN, are analyzed as a case study. Sustainability facets of waste management, resource utilization and economics are in focus.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

A rapid, precise, accurate and low cost method for the determination of vitamin E (α-tocopherol) in cereal products and biscuits was developed. The uncertainty was calculated for the first time and the methods were performed in different cereal products and biscuits, characterized as “superfoods”. The limits of detection and quantification were calculated. Accuracy and precision were estimated using the certified reference material FAPAS T10112QC and the determined values were in good accordance with the certified values. The health claims according to the daily reference values for vitamin E were calculated and the results proved that the majority of the samples examined showed %daily value higher than 15%.

The theories of quantum mechanics and relativity dramatically altered our understanding of the universe ushering in the era of modern physics. Quantum theory deals with objects probabilistically at small scales, whereas relativity deals classically with motion in space and time. We show here that the mathematical structures of quantum theory and of relativity follow together from pure thought, defined and uniquely constrained by the same elementary ``combining and sequencing'' symmetries that underlie standard arithmetic and probability. The key is uncertainty, which inevitably accompanies observation of quantity and imposes the use of pairs of numbers. The symmetries then lead directly to the use of complex \sqrt{-1} arithmetic, the standard calculus of quantum mechanics, and the Lorentz transformations of relativistic spacetime. One dimension of time and three dimensions of space are thus derived as the profound and inevitable framework of physics.

Phenomenon of vacuum fluctuations of virtual particles in high energy physics has been mathematically modeled by a third order differential equation. Aim of present theory is to unravel underlying mathematical equation capable of explaining microscopic phenomenon of vacuum fluctuations. Solution of such a differential equation after applying appropriate boundary conditions gives an acceptable wave function i.e. . Operation of energy and time operator on this wave function proves that these operators do not hold commutative property. Time energy uncertainty principle has been derived by calculating variance of energy and time for the same wave function.

Future projections from climate models and recent studies shows impact of climate change on rainfall indices estimation. This study assesses the simulations of rainfall indices based on the Coupled Model Intercomparison Project CMIP5 and CMIP3 in the some of subbasin Hamedan Province West of Iran. The analysis of the rainfall indices are: simple rainfall intensity, very heavy rainfall days, maximum one-day rainfall and rainfall frequency has been carried out in this study to evaluating the impact of climate change on rainfall indices events. Relative change in three rainfall indices is investigated by GCMs under various greenhouse gas emission scenarious A1B and B1 and RCP8.5, RCP8.5 scenarios for the future periods 2020–2045 and 2045-2065. The final results show that each of rainfall indices differs in stations under the three GCMs model (GIAOM, MIHR, MPEH5) and emission scenarios A1B and B1, and RCP2.5, RCP8.5 scenarios. Relative change of daily intensity index varies from -9.93% - 25%, very heavy rainfall days 20.71% - 25.9% and yearly rainfall depth -15.71% - 13% can be observed at study area in 50y for future periods (2046–2065). Rainfall indices of sum wet days, nday >1mm and maximum one-day rainfall are projected to decrease under the senariuos B1,A1B and sum wet days, simple daily intensity and heavy Rainfall days>10 projected to decrease under the RCP2.6.

The energy, momentum and the action associated with the time domain transition radiation fields are investigated. The results show that for a charged particle moving with speed $v$, the longitudinal momentum associated with the transition radiation is approximately equal to $E/c$ for values of $1-v/c$ smaller than about 10^-3 where $E$ is the total radiated energy and c is the speed of light in free space. The action of the transition radiation, defined as the product of the energy dissipated and the duration of the emission, increases as $1-v/c$ decreases and, for an electron, it becomes equal to $h/4\pi$ when $v=c-v_m$ where $v_m$ is the speed associated with the lowest energy state of a particle confined inside the universe and h is the Plank constant. Combining these results with Heisenberg’s uncertainty principle, an expression for the electronic charge based on other fundamental physical constants is derived. The best agreement between the experimentally observed electronic charge and the theoretical prediction is obtained when one assumes that the actual size of the universe is about 250 times larger than the visible universe.

Load balancing, energy efficiency and fault tolerance are among the most important data dissemination issues in Wireless Sensor Networks (WSNs). In order to successfully cope with the mentioned issues, two main approaches (namely, Data-centric Storage and Distributed Data Storage) have been proposed in the literature. Both approaches suffer from data loss due to memory and/or energy depletion in the storage nodes. Even though several techniques have been proposed so far to overcome the mentioned problems, the proposed solutions typically focus on one issue at a time. In this paper, we integrate the Data-centric Storage (DCS) features into Distributed Data Storage (DDS) mechanisms and present a novel approach, denoted as Collaborative Memory and Energy Management (CoMEM), to overcome both problems and bring memory and energy efficiency to the data loss mechanism of WSNs. We also propose analytical and simulation frameworks for performance evaluation. Our results show that the proposed method outperforms existing approaches in various WSN scenarios.

Delineating the cropping area of cocoa agroforests is a major challenge for quantifying the contribution of the land use expansion to tropical deforestation. Discriminating cocoa agroforests from tropical transition forests using multi-spectral optical images is difficult due to a similarity in the spectral characteristics of their canopy; moreover, optical sensors are largely impeded by the frequent cloud cover in the tropics. This study explores multi-season Sentinel-1 C-band SAR image to discriminate cocoa agroforests from transition forests for a heterogeneous landscape in central Cameroon. We use an ensemble classifier, random forest, to average SAR image texture features of GLCM (Grey Level Co-occurrence Matrix) across seasons; next, we compare classification performance with results from RapidEye optical data. Moreover, we assess the performance of GLCM texture feature extraction at four different grey level quantization: 32bits, 8bits, 6bits, and 4bits. The classification overall accuracy (OA) of texture-based maps outperformed that from an optical image; the highest OA of 88.8% was recorded at 6bits grey level. This quantization level, in comparison to the initial 32bits in SAR images, reduced the class prediction error by 2.9%. Although this prediction gain may be large for the landscape area, the resultant thematic map reveals the decrease and fragmentation of forest cover by cocoa agroforests. According to our classification validation, the Shannon entropy (H) or uncertainty provides a reliable validation for class predictions and reveals detail inference for discriminating inherently heterogeneous vegetation categories. The texture-based classification achieved a reliable accuracy considering the heterogeneity of the landscape and vegetation classes.

In this study, we evaluated the potential of fungal endophytes to control yellow rust in wheat (Triticum aestivum L.) as endophytes are beneficial microbes and alternate to pesticides for confronting pathogens. The in-vitro efficacy of the fungal endophytes isolated from different desert plants was evaluated and the best four namely Colletotrichum lindemuthianum, Piriformospora indica, Acremonium lolii and Trichoderma viride were selected. Seeds of two susceptible wheat genotypes namely Fareed-06 and Shafaq-06 obtained from screening experiment were inoculated by dipping in four endophytic spore suspensions and were sown using randomized complete block design under factorial arrangement. Data concerning about area under disease progress curve, final disease severity percentage, coefficient of infection,1000- grains weight and grain yield were recorded. Results showed that endophyte P. indica showed significant decrease in final disease severity (FDS) and area under disease progress curve (AUDPC), resultantly 12.2% grain yield gain in rust susceptible wheat genotypes of Fareed-06 and Shafaq-06 followed by the endophytes T. viride, C. lindemuthianum and A. lolii with the grain yield gain of 10.6%, 06.2% and 04.2% respectively. In crux, fungal endophytes are valuable microbes which can be employed to induce tolerance against P. striiformis in yellow rust vulnerable areas for better and sustainable wheat production.

This work assesses sea-level rise using three different models created on Free and Open-Source Software for Geographic Information System (FOSS4GIS). Based on regional projections of Special Report on Climate Change and Oceans and Cryosphere (SROCC) of the Intergovernmental Panel on Climate Change (IPCC), the models were applied to a case of study on Rio Grande do Sul coast – Brazil under different sea-level rise scenarios by the end of this century. The End Point Rate for QGIS (EPR4Q), calculates a shoreline projection using End Point Rate method. The Uncertainty Bathtub Model (uBTM), analyses the sea-level rise impact by the uncertainty of sea-level projec-tions and vertical error of the Digital Elevation/Terrain Model (DEM/DTM). The Bruun Rule for Google Earth Engine Model (BRGM) predicts the shoreline position with sea-level rise, using topographic and bathymetric data from Unmanned Aerial Vehicles (UAV) and Coastal Modelling System (SMC – Brazil), respectively. The results indicated a maximum shoreline retreat for 2100 of -502 m and -1727 m using EPR4Q and BRGM, correspondingly. The uBTM using the land-use of Mapbiomas showed a maximum of 44.57 km2 of urban area impacted by the sea-level flood. This research highlights the possibility of performing coastal management analysis in GIS environ-ment using non-commercial software.

We propose a methodology for the quantification of model risk in the context of credit derivatives pricing and CVA, where the uncertain or unmodelled parameter is often the correlation between rates and credit. We take the rates model to be Hull-White (normal) and the credit model to be Black-Karasinski (lognormal). We show how highly accurate analytic pricing formulae, hitherto unpublished, can be derived for CDS and extended to address instruments with defaultable Libor flows which may in addition be capped and/or floored. We also consider the pricing of a contingent CDS with an interest rate swap underlying. We derive explicit expressions showing how to good accuracy the dependence of model prices on the uncertain parameter(s) can be captured in analytic formulae which are readily amenable to computation without recourse to Monte Carlo or lattice-based computation. In so doing, we take into account the impact on model calibration of the uncertain (or unmodelled) parameter.

Recent researches proved that the underbridge geometry can be reconstructed by mounting a 3D laser scanner on a motorized cart travelling on a walkway located under the bridge. The walkway is moved by a truck and the accuracy of the bridge model depends on the accuracy of the trajectory of the scanning head with respect to a fixed reference system. In this paper, we describe the metrological characterization of a method that uses non-contact systems to identify the relative motion of the cart with respect to the walkway; the orientation of the walkway with respect to the bridge is determined using inclinometers and optical rails, while the position of the truck with respect to the bridge is measured using a conventional odometer. The measurement uncertainty of the proposed system was initially evaluated by numerical simulations and successively verified by experiments in laboratory conditions. The complete system has then been tested in operative conditions; the validity of the proposed approach has been demonstrated by comparing the geometry of buildings reconstructed with the proposed system with the geometry obtained with a static scan. Results evidenced that the errors are approximately 6 mm.

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. The interpretation regarding agreement is based on whether B-A limits are within the pre-specified clinical tolerance. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that such limits of clinical tolerance can be directly used for assessing agreement and plead that this nonparametric approach is simple and robust to the distribution pattern and outliers. Such direct use of clinical tolerance limits has more flexibility, and it is more effective in assessing the extent of agreement.

Model-based design has received considerable attention in biological and chemical industries over the last two decades. However, the parameter uncertainties of first-principle models are critical in model-based design and have led to the development of robustification concepts. Various strategies were introduced to solve the robust optimization problem. Most approaches suffer from either unreasonable computational expense or low approximation accuracy. Moreover, they are not rigorous and do not consider robust optimization problems where parameter correlation and equality constraints exist. In this work, we propose a highly efficient framework for solving robust optimization problems with the so-called point estimation method (PEM). The PEM has a fair trade-off between computation expense and approximation accuracy and can be easily extended to problems of parameter correlations. From a statistical point of view, moment-based methods are used to approximate robust inequality and equality constraints. We also suggest employing the information from global sensitivity analysis to further simplify robust optimization problems with a large number of uncertain parameters. We demonstrate the performance of the proposed framework with two case studies where one is to design a heating/cooling profile for the essential part of a continuous production process and the other is to optimize the feeding profile for a fed-batch reactor of the penicillin fermentation process. The results reveal that the proposed approach can be used successfully for complex (bio)chemical problems in model-based design.

Heat stress occurring during the reproductive stage of wheat has a detrimental effect on productivity. A durum wheat core set was exposed to simulated terminal heat stress by applying plastic tunnels at the time of flowering over two seasons. Mean grain yield was reduced by 54% compared to control conditions, and grain number was the most critical trait for tolerance to this stress. The combined use of tolerance indices and grain yield identified five elites: Kunmiki, Berghouata1, Margherita2, IDON37-141, and Ourgh. The core set was also subjected to genome wide association study using 7,652 polymorphic SNPs markers. The most critical genomic regions were identified in association with spike fertility and tolerance indices on chromosome 1A, 5B and 6B. Haplotype analysis on a set of 208 elites confirmed that lines that carried the positive allele at all three QTLs resulted in a yield advantage of 8% when field tested under daily temperatures above 31° C. Two of the QTLs were successfully validated into KASP markers and explained >10% of the phenotypic variation for an independent elite germplasm set. These genomic regions can now be readily deployed via breeding to improve resilience to climate change and increase productivity in heat-stressed areas.

SARS-CoV-2, the virus that causes theCOVID-19 disease, has been demonstrated to cause immune suppression in certain individuals. This can manifest as a reduced ability for the host's immune system to effectively control the infection. Studies have reported that patients with COVID-19 can exhibit a decline in white blood cell counts, including natural killer cells and T cells, which are integral components of the immune system's response to viral pathogens. These cells play critical roles in the immune response to viral infections, and their depletion can make it harder for the body to mount an effective defense against the virus. Additionally, the virus can also directly infect immune cells, further compromising their ability to function. Some individuals with severe COVID-19 pneumonia may develop a "cytokine storm," an overactive immune response that may result in tissue damage and organ malfunction. The underlying mechanisms of immune suppression in SARS-CoV-2 are not entirely comprehended at this time, and ongoing research is being conducted to gain a more comprehensive understanding. Research has shown that severe SARS-CoV-2 infection promotes the synthesis of IgG4 antibodies. In this work, we propose the hypothesis that the IgG4 antibody produced by B cells in response to infection by SARS-CoV2 generates immunological tolerance that prevents its elimination, and leads to persistence and chronic infection. In sum, we believe that this constitutes another immune evasion mechanism that bears striking similarities to that developed by cancer cells to evade immune surveillance.

Accurate and reliable project cost estimates are fundamental to achieve successful municipal capital improvement (CIP) programs. Engineering cost estimates typically represent critical information for key decision makers to authorize and efficiently allocate the necessary funds for construction, budgeting, to generate a request for proposals, contract negotiations, scheduling, etc. for these reasons, cost estimators are using different estimating methods and approaches that allow for required levels of accuracy. As the project’s scope becomes more detailed and the potential risks are identified and/or the project design stage progresses these cost estimates are revised and updated. In this paper, the most common project cost estimation methods and approaches were collected and categorized into two main groups of (1) probabilistic and (2) deterministic methods. Under these groups overall ten different methods were identified and discussed addressing their requirements, advantages, and shortcomings, including the potential risk that can positively or negatively affect the project’s cost outcome. This paper will be a good resource for professionals who are in budget development and/or are seeking to a better understanding of different methods in determining an appropriate base cost margin and produce a meaningful and reliable project cost estimate.

A quantum time-dependent spectrum analysis, or simply, quantum spectral analysis (QSA) is presented in this work, and it’s based on Schrödinger’s equation. In the classical world, it is named frequency in time (FIT), which is used here as a complement of the traditional frequency-dependent spectral analysis based on Fourier theory. Besides, FIT is a metric which assesses the impact of the flanks of a signal on its frequency spectrum - not taken into account by Fourier theory and let alone in real time. Even more, and unlike all derived tools from Fourier Theory (i.e., continuous, discrete, fast, short-time, fractional and quantum Fourier Transform, as well as, Gabor) FIT has the following advantages, among others: a) compact support with excellent energy output treatment, b) low computational cost, O(N) for signals and O(N2) for images, c) it does not have phase uncertainties (i.e., indeterminate phase for a magnitude = 0) as in the case of Discrete and Fast Fourier Transform (DFT, FFT, respectively). Finally, we can apply QSA to a quantum signal, that is, to a qubit stream in order to analyze it spectrally.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

We present a generalized state-space model formulation particularly motivated by an online scheduling perspective. Through these proposed generalizations, we enable a natural way to handle routinely encountered disturbances and a rich set of corresponding counter-decisions. Thereby, greatly simplifying and extending the possible application of mathematical programming based online scheduling solutions to diverse application settings.

A new requirement for the manufacturing companies in Industry 4.0 is to be flexible with respect to changes in demands, requiring them to react rapidly and efficiently on the production capacities. Together with the trend to use Service-Oriented Architectures (SOA), this requirement induces a need for agile collaboration among supply chain partners, but also between different divisions or branches of the same company. In order to address this collaboration challenge, we~propose a novel pragmatic approach for the process analysis, implementation and execution. This~is achieved through sets of semantic annotations of business process models encoded into BPMN 2.0 extensions. Building blocks for such manufacturing processes are the individual available services, which are also semantically annotated according to the Everything-as-a-Service (XaaS) principles and stored into a common marketplace. The optimization of such manufacturing processes combines pattern-based semantic composition of services with their non-functional aspects. This is achieved by means of Quality-of-Service (QoS)-based Constraint Optimization Problem (COP) solving, resulting in an automatic implementation of service-based manufacturing processes. The produced solution is mapped back to the BPMN 2.0 standard formalism by means of the introduced extension elements, fully detailing the enactable optimal process service plan produced. This approach allows enacting a process instance, using just-in-time service leasing, allocation of resources and dynamic replanning in the case of failures. This proposition provides the best compromise between external visibility, control and flexibility. In this way, it provides an optimal approach for business process models' implementation, with a full service-oriented taste, by implementing user-defined QoS metrics, just-in-time execution and basic dynamic repairing capabilities. This paper presents the described approach and the technical architecture and depicts one initial industrial application in the manufacturing domain of aluminum forging for bicycle hull body forming, where the advantages stemming from the main capabilities of this approach are sketched.

SLEUTH Model (slope, landuse, exclusion, urban extent, transportation and hillshade) is an important tool for landuse planning and land policy. To evaluate the performance of SLEUTH model, implementation of Sensitivity Analysis (SA) is essential. The main limitation of SA in SLEUTH application is a lack of insight into model input self-modification parameters (SMPs) variation, namely, uncertainty involved in the model transfer metrics and model presumptions, which often misled the decision makers and model users. To address this issue, this study divided the forward process into two stages. Firstly, during the transfer process ①, the contribution scores of five SMPs were drawn, and parameters highly sensitive to model output were given. Apart from that, the recommended initial value for SMPs of 0.11, 0.2, 0.87, 1.13, 15, 1.01, 0.49 were found to be subordinated to such a heterogeneous urban area simulation. Secondly, during the transfer process ②, SMP caused imagery metrics indicated the disparity between parameters with Fixed Reference and with Successive Reference. Reversely, it derives reasonable threshold for the best fit values of five prediction coefficients’ initialization by comparing the real image with the predicted one. The framework of SLEUTH model transfer mechanism not only could distinguish highly sensitive SMPs with higher contribution scores, but also could give parametric analysis for simulation imagery based on metrics. The study was found to be a practical tool for quantization response of model input variables for modelling complex urban systems. So, this insight can help geographic information scientists decide how to find out the inner forward transfer mechanism of SLEUTH model for further make good use of it and improve the model.

: Mistrust, amplified by numerous artificial intelligence (AI) related incidents, has caused the energy and industrial sectors to be amongst the slowest adopter of AI methods. Central to this issue is the black-box problem of AI, which impedes investments and fast becoming a legal hazard for users. Explainable AI (XAI) is a recent paradigm to tackle this challenge. Being the backbone of the industry, the prognostic and health management (PHM) domain has recently been introduced to XAI. However, many deficiencies, particularly lack of explanation assessment methods and uncertainty quantification, plague this young field. In this paper, we elaborate a framework on explainable anomaly detection and failure prognostic employing a Bayesian deep learning model to generate local and global explanations from the PHM tasks. An uncertainty measure of the Bayesian model is utilized as marker for anomalies expanding the prognostic explanation scope to include model’s confidence. Also, the global explanation is used to improve prognostic performance, an aspect neglected from the handful of PHM-XAI publications. The quality of the explanation is finally examined employing local accuracy and consistency properties. The method is tested on real-world gas turbine anomalies and synthetic turbofan data failure prediction. Seven out of eight of the tested anomalies were successfully identified. Additionally, the prognostic outcome showed 19% improvement in statistical terms and achieved the highest prognostic score amongst best published results on the topic.

The description of the microscopic world in quantum mechanics is very different from that in classical physics, and there are some points of view that are contrary to intuition and logic. The first is the loss of reality, the behavior of micro particles shows randomness and hopping. The second is the loss of certainty, the conjugate physical variables of a system cannot be determined synchronously, they satisfy the Heisenberg uncertainty principle. The third is the non-local correlation. The measurement of one particle in the quantum entanglement pair will change the state of the other entangled particle simultaneously. In this paper, some concepts related to quantum entanglement, such as EPR correlation, quantum entanglement correlation function, Bell's inequality and so on, are analyzed in detail. Analysis shows that the mystery and confusion in quantum theory may be caused by the logical problems in its basic framework. Bell's inequality is only a mathematical theorem, but its physical meaning is actually unclear. The Bell state of quantum entangled pair may not satisfy the dynamic equation of quantum theory, so it cannot describe the true state of microscopic particles. In this paper, the correct correlation functions of spin entanglement pair and photonic entanglement pair are strictly derived according to normal logic. Quantum theory is a more fundamental theory than classical mechanics, and they are not parallel relation in logic. However, there are still some unreasonable contents in the framework of quantum theory, which need to be improved. In order to disclose the real relationship between quantum theory and classical mechanics, we propose some experiments which show the wave-particle duality simultaneously and provide intuitionistic teaching materials for the new interpretation of quantum theory.

Energy Measurement and Verification (M&V) aims to make inferences about the savings achieved in energy projects, given the data and other information at hand. Traditionally, a frequentist approach has been used to quantify these savings and their associated uncertainties. We demonstrate that the Bayesian paradigm is an intuitive, coherent, and powerful alternative framework within which M&V can be done. Its advantages and limitations are discussed, and two examples from the industry-standard International Performance Measurement and Verification Protocol (IPMVP) are solved using the framework. Bayesian analysis is shown to describe the problem more thoroughly and yield richer information and uncertainty quantification than the standard methods while not sacrificing model simplicity. We also show that Bayesian methods can be more robust to outliers. Bayesian alternatives to standard M&V methods are listed, and examples from literature are cited.

Soil hydraulic properties are often derived indirectly, i.e. computed from easily available soil properties with pedotransfer functions (PTFs), when those are needed for catchment, regional or continental scale applications. When predicted soil hydraulic parameters are used for the modelling of the state and flux of water in soils, uncertainty of the computed values can provide more detailed information when drawing conclusions. The aim of this study was to update the previously published European PTFs (Tóth et al., 2015, euptf v1.4.0) by providing prediction uncertainty calculation built into the transfer functions. The new set of algorithms was derived for point predictions of soil water content at saturation (0 cm matric potential head), field capacity (both -100 and -330 cm matric potential head), wilting point (-15.000 cm matric potential head), plant available water, and saturated hydraulic conductivity, as well as the Mualem-van Genuchten model parameters of the moisture retention and hydraulic conductivity curve. The minimum set of input properties for the prediction is soil depth and sand, silt and clay content. The effect of including additional information like soil organic carbon content, bulk density, calcium carbonate content, pH and cation exchange capacity were extensively analysed. The PTFs were derived adopting the random forest method. The advantage of the new PTFs is that they i) provide information about prediction uncertainty, ii) are significantly more accurate than the euptfv1, iii) can be applied for more predictor variable combinations than the euptfv1, 32 instead of 5, and iv) are now also derived for the prediction of water content at -100 cm matric potential head and plant available water content.

At present more than 9 million people die of cancer every year. Simple and broad-spectrum drugs are still an urgent need for cancer patients. Recently, we proposed a new hypothesis that intracellular osmotic pressure (IOP) is the driving force of cell division, and abnormal tumor proliferation is the result of uncontrolled IOP in cells. On the one hand, aneuploidy and abnormal function of Na⁺/K⁺ pump lead to a faster rise of IOP in tumor cell than normal cells, on the other hand, abnormality of cytoskeleton assembly leads to the decrease of tolerance limit of cell membrane (TLCM) of tumor cells for resisting IOP. This hypothesis predicts: 1)Tumor cells were more intolerant to hypotonic stress than normal cells. 2) Maligancies may be sellectively killed by a suddenn increase of IOP and combined with decrease of the TLCM of tumors. Na⁺/K⁺ pump inhibitors can promotely increase the IOP of tumor cells and cytoskeleton inhibitors can dramatically lower the TLCM of tumor cells. Therefore, Na⁺/K⁺ pump and cytoskeleton inhibitors may have a synergetic effect to kill tumor cells. 3) Molecules regulating cell osmolality may be new targets for cancer treatment.

Drought is one of the major stress factors affecting growth and development of plants. In this context, drought-related losses of crop plant productivity impede sustainable agriculture all over the world. In general, plants responses to water deficit by multiple physiological and metabolic adaptations at the molecular, cellular and organism levels. To understand the underlying mechanisms of drought tolerance, adequate stress models and arrays of reliable stress markers are required. Therefore, in this review we comprehensively address currently available models of drought stress, based on culturing plants in soil, hydroponic or agar culture. These experimental setups give access to different aspects of plant response to drought, like decrease of tissue water potential, reduction of stomata conductance and photosynthesis efficiency, accumulation of low-molecular weight solutes (metabolic adjustment) and drought protective proteins. Till now, this pattern of markers was successfully extended to the methods of enzyme chemistry, molecular biology and omics techniques. Thus, conventional tests can be efficiently complemented by determination of phytohormone and reactive oxygen species (ROS) contents, activities of antioxidant enzymes, as well as comprehensive profiling of transcriptome, proteome and metabolome.

Over a billion people live in slums, with poor sanitation, education, property rights and working conditions having direct impact on current residents and future generations. A key problem in relation to slums is slum mapping. Without delineations of where all slum settlements are, informed decisions cannot be made by policymakers in order to benefit the most in need. Satellite images have been used in combination with machine learning models to try and fill the gap in data availability of slum locations. Deep learning has been used on RGB images with some success but since labeled satellite images of slums are relatively low quality and the physical/visual manifestation of slums significantly varies within and across countries, it is important to quantify the uncertainty of predictions for reliable application in downstream tasks. Our solution is to train Monte Carlo dropout U-Net models on multispectral 13-band Sentinel-2 images from which we can calculate pixelwise epistemic (model) and aleatoric (data) uncertainty in our predictions. We trained our model on labelled images of Mumbai and verified our epistemic and aleatoric uncertainty quantification approach using altered models trained on modified datasets. We also used SHAP values to investigate how the different features contribute towards the model’s predictions and this showed that certain short-wave infrared and red-edge image bands are powerful features for determining the locations of slums within images. Having created our model with uncertainty quantification, in the future it can be applied to downstream tasks and decision-makers will know where predictions have been made with low uncertainty, giving them greater confidence in its deployment.

Abiotic stresses, including drought, salinity, cold, heat, and heavy metals, extensively reduce global agricultural production. Approaches such as conventional breeding and transgenic breeding have been widely used to cope with these environmental stresses. The clustered regularly interspaced short palindromic repeat- Cas (CRISPR/Cas) based gene-editing tool has revolutionized due to its simplicity, accessibility, adaptability, flexibility, and wide applicability. This system has a great potential to build up crop varieties with enhanced tolerance against abiotic stresses. In this review, we summarize the most recent findings on understanding the mechanism of abiotic stress response in plants and the application of CRISPR/Cas mediated gene-editing system towards enhanced tolerance to drought, salinity, cold, heat, and heavy metals stresses. Furthermore, in this review, we highlighted the recent advancements in prime editing and base editing tools for crop improvement.

Starting from unidentified objects moving inside a two-dimensional Euclidean manifold, we propose a simple method to detect the topological changes that occur during their reciprocal interactions and shape morphing. This method, which allows the detection of topological holes development and disappearance, makes it possible to solve the uncertainty due to disconnectedness, lack of information and absence of objects’ sharp boundaries, i.e., the three troubling issues which prevent scientists to select the required proper sets/subsets during their experimental assessment of natural and artificial dynamical phenomena, such as fire propagation, wireless sensor networks, migration flows, neural networks’ and cosmic bodies’ analysis.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Background: The COVID-19 pandemic has hit the Spanish economy hard. The result is an unprecedented economic and social crisis due to uncertainty about the remedy, and due to the socio-economic effects on people’s lives. Methods: We performed a retrospective analysis of the macro-economic impact of COVID-19 in 2020, using the principal indicators of the Spanish economic and productive model. National statistics were examined in the search for impacts or anomalies occurring since the beginning of the pandemic. To estimate the strength of the impact on each of the indicators analysed, we used Bayesian structural time series. Results: In 2020, the cumulative impact on the Gross Domestic Product was of -11.41% [95% credible interval: -13.46; -9.29]. The indicator for Business Turnover fell by -9.37% [-12.71; -6.07]. The reduction in business activity was related to the sharp fall in demand. The Spanish employment market was strongly affected; our estimates showed a cumulative increase of 11.9% [4.27; 19.45] in the rate of unemployment during 2020. The autonomous communities which are economically the most heavily dependent on the services sector were those which recorded the worst indicators. Conclusions: Our estimates portray a dramatic situation in our country, and show all too clearly the fragility of a productive system which has to make the behavioural changes that are necessary to confront the COVID-19 pandemic.

The experiments of Project 8 have been excellent, but the expected goals still difficult to achieve. So much so that some of the results at your fingertips were also missing. In view of this, the focus of this article is to clarify several easy confused concepts. Only in this way, we can reasonably explain the experimental data. The main points are as follows: 1. The value c of the light speed in vacuum and a particle with zero static mass, both of which do not exist in the reality. That is to say, the so-called a photon's static mass is equal to zero but has energy, which is a paradox that confuses two different definitional domains. 2. In the reality, photons are high-speed particles generated by electromagnetic radiation. They must have the characteristics of (static) mass, energy and wave, in order to describe the main body to aim at photons from different angles. 3. After any main body comes into being electromagnetic radiation, its static mass will inevitably decrease accordingly. 4. The charge-mass ratio of an electron is a physical constant, which is the ratio of its charge to the amount of matter, and is not affected by relativistic effects and electromagnetic radiation. 5. The uncertainty of moving electrons is caused by random electromagnetic radiations. Finally, it is pointed out that if the cyclotron frequency of a single electron is measured, and at the same time, its de Broglie wavelength or frequency can also be measured, then its static mass can be obtained. Even so, the expected goals are still difficult to achieve, because random electromagnetic radiations are always taking away continually the matter composition of the single electron being measured. However, this was precisely a result of the research obtained by Project 8, and had universality, which should be reflect on.

Low temperature is a common biological abiotic stress in major cotton growing areas. Cold stress significantly affects the growth, yield and yield quality of cotton. Therefore, it is important to develop a more robust and cold stress tolerant cotton germplasms. Climate change and erratic climatic condition, plants have evolved various survival mechanisms, one of which induction of various stress responsive transcriptome factors, such as the C-repeat binding factor GthCBF4, which have been found to enhance cold tolerance in various plants. In this study detailed evaluation of the cotton C-repeat binding factor has been carried out. A total of29, 28, 25, 21, 30, 26 and 15 proteins encoded by the C-repeat binding factor were identified in G. herbaceum, G. arboreum, G. thurberi, G. raimondii, G. turneri, G. longicalyx and G. australe, respectively. Phylogeny evaluation revealed that the proteins were grouped into seven clades, with clade 1 and 6 being the largest. Moreover, majority of the proteins encoded by the genes were predicted to be located within. the nucleus, while some are distributed in other parts of the cell. Based on the transcriptome and RT-qPCR analysis, Gthu17439 (GthCBF4) was highly upregulated and was further validated through forward genetics. The Gthu17439 (GthCBF4) overexpressed plants showed a significantly tolerance to cold stress, with higher growth vigour compared to the wild types. The results showed that the Gthu17439 (GthCBF4) could be playing a significant role in enhancing cold stress tolerance in cotton and can be further exploited in developing a more cold stress tolerance cotton germplasm

A modular switched-capacitor (SC) DC-DC converter (MSCC) is introduced in this paper. It is designed to boost a low input voltage to a high voltage level and can be applied for photovoltaics and electric vehicles. This topology has high extensibility for high voltage gain output. The merits of the converters also lie in the fault tolerance operation and the voltage regulation with a minimum change in the duty ratio. Those features are built in when designing the modules and then integrating these into the DC-DC converter. Converter performance including voltage gain, voltage and current stress are focused and tested. The converter is modelled analytically, and its control algorithm is analyzed in detailed. Both simulation and experiment are carried out to verify the topology under normal operation and fault mode operation.

Indonesia is an archipelago with diverse ethnicities, races, languages, cultures, beliefs, and customs. As Indonesians, with these differences, they should respect each other, or what is commonly known as tolerance. However, in the 21st century, tolerance between people in Indonesia is starting to fade. This is due to the development of the times accompanied by technology development, which causes globalization to enter quickly. The culture of tolerance typical of Indonesian society is starting to fade due to the influence of globalization. Based on these problems, this study aims to determine what causes the decline intolerance of Indonesian society in the 21st century and answer what solutions can be given to prevent the decline intolerance of Indonesian society in the 21st century. The research method used is descriptive-qualitative through literature review by analyzing data following the topic to be discussed. The data used are from 20 journal articles with a span of 2019-2021. The results of this study are in the form of a decline in intolerance that the Indonesian people own due to technological advances in the form of adverse use of social media. However, with the existence of moral education and the role of teachers and the government to overcome the decline intolerance, it is hoped that the Indonesian people will understand the meaning and importance of tolerance. This study also has limitations, namely only on the causes of the fading of tolerance in Indonesian society.

The classical uncertainty principle inequalities were imposed as a mathematical constraint over the general relativity geodesic equation. In this way, the uncertainty principle was reformulated in terms of the proper space-time length element, Planck length and a geodesic-derived scalar, leading to a geometric expression for the uncertainty principle (GeUP). This re-formulation confirmed the necessity for a minimum length for the space-time line element in the geodesic, dependent on a geodesic-derived scalar which made the expression Lorentz-covariant. In agreement with quantum gravity theories, GeUP required the imposition of a perturbation over the background Minkowski metric unrelated to classical gravity. When applied to the Schwarzschild metric, a geodesic exclusion zone was found around the singularity where uncertainty in space-time diverged to infinity.

Five-day exposure of clary sage (Salvia sclarea) to 100 μM cadmium (Cd) in hydroponics was sufficient to increase Cd concentrations significantly in roots and aboveground parts and affect negatively whole plant levels of calcium (Ca) and magnesium (Mg), since Cd competes for Ca channels, while reduced Mg concentrations are associated with increased Cd tolerance. Total zinc (Zn), copper (Cu), and iron (Fe) uptake increased but their translocation to the aboveground parts decreased possible due to translocation barriers. Despite the substantial levels of Cd in leaves, without any observed defects on chloroplast ultrastructure, an enhanced photosystem II (PSII) efficiency was observed, with a higher fraction of absorbed light energy to be directed to photochemistry (ΦPSΙΙ). The concomitant increase in the photoprotective mechanism of non-photochemical quenching of photosynthesis (NPQ) resulted in an important decrease in the dissipated non-regulated energy (ΦNO), modifying the homeostasis of reactive oxygen species (ROS), through a decreased singlet oxygen (1O2) formation. Thus, when clary sage was exposed to Cd for a short period, tolerance mechanisms were triggered, with PSII photochemistry to be regulated by NPQ in such a way that PSII efficiency to be enhanced. However, exposure to a combination of Cd and high light or for longer duration (8 days) to Cd alone, resulted in an inhibition of PSII functionality pointing out towards Cd toxicity. Thus, the rapid activation of PSII functionality at short time exposures and the inhibition at longer duration suggests a hormetic response and describes these effects in terms of “adaptive response” and “toxicity”, respectively.

Candida glabrata has thoroughly adapted to successfully colonize human mucosal membranes and survive in vivo pressures prior to and during antifungal treatment. Out of all the medically relevant Candida species, C. glabrata has emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole + echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic to C. glabrata, since stable genetic resistance depends on mutation of drug target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription factor, PDR1, which controls expression of major drug transporters, such as CDR1 (azole resistance). However, another hallmark of C. glabrata is the ability to withstand drug pressure both in vitro and in vivo prior to stable ‘genetic escape’. Additionally, these resistance events can arise within individual patients, which underscores the importance of understanding how this fungus is adapting to its environment and to drug exposure in vivo. Here, we explore the evolution of echinocandin resistance as a multistep model that includes general cell stress, drug adaptation (tolerance), and genetic escape. The extensive genetic diversity reported in C. glabrata will be highlighted.

As a result of the cancer immunotherapy revolution hundreds of clinical trials of the newly approved immunotherapies are now under way to improve responses. Not unexpectedly, the 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo for their development of cancer therapy by blockade of co-inhibitory signals. While success stories of terminal cancer patients achieving complete remissions are accumulating, not enough research has been done into the risks of the new therapies. Since the use of immunotherapy is becoming more common, and is expected to develop into first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the nemesis of immunotherapy. Immune-related adverse events (IrAEs) could affect any tissue, their incidence may reach up to 90% of patients and toxicity is dose-dependent. While the combination of two immune checkpoint inhibitors (ICIs) increased efficacy, the incidence of severe adverse events was also increased. Apparently, ICIs cannot be restricted to the targeted anti-tumor T cell population. The long lasting objective of cancer regression can only be achieved by paying a price: tolerance to healthy self tissues is compromised. In the face of an ipilimumab induced pan-lymphocytic activation, a therapeutic paradigm shift is required. The task is not desperately trying to put the genie back in the bottle by immune suppressive treatments, but instead harnessing the autoimmune forces by an off label low-dose combined anti-CTLA-4 and anti-PD1 antibody blockade, which is supplemented with conventional interleukin-2 stimulation and hyperthermia. The proof-of-principle of the low-dose-combination therapy was demonstrated in a heavily pre-treated triple negative breast cancer (TNBC) patient with far advanced pulmonary metastases and severe shortness of breath, who had exhausted all conventional treatment. Her pulmonary metastases went into complete remission with transient WHO I-II diarrhea and skin rash. She lived for 27 months after starting the low-dose-combination therapy. She had recurrence as a sternal mass and pleural metastases up to 3 cm. Since the low-dose-combination protocol consists only of approved drugs and treatments, this exceptional response should instigate further research efforts.

Since the beginning, humans advanced their civilization by making better tools to improve their lives. Tools and products were designed for better living considering manufacturing issues, cost and time as predominant criteria. It has become clear that not considering environment and society, both at local/global levels, has now become a major impediment affecting living conditions on a large portion of the Earth and in many societies. Design methodologies should lead to creative solutions with consideration to engineering and economics for practicality but also to environmental and social constraints for sustainability. We propose a comprehensive design methodology based on multidisciplinary design to include the knowledge of humanities, environmentalists, science and engineering, and allowing for experts’ inputs from these areas to provide a holistic approach to engineering design . For example, experts in humanities are expected to interact with stakeholders to evaluate their value systems to provide guidance for the design. The methodology that we synthesize is new and combines (i) Societal level impacts at all scales, (ii) Environmental impacts and (iii) Engineering design with economic impacts, including uncertainty considerations. The proposed design methodology is called Social-Environmental-Economical-Engineering Framework (SEEEF). It can utilize concepts and tools such as Circular Design, Doughnut Economics, design based on environmental life cycle analysis, among others. SEEEF is quantity based and provides steps for evaluating any project or product in an objective manner and will help train engineers in design for sustainability. It also provides non-engineers with a significant role in design to increase their understanding of the hard constraints of engineering. Ultimately, SEEEF allows society to take an informed decision considering short/long term and local/global impacts of the design and the pertinent uncertainties.

This paper introduces a surrogate model to reduce the huge computational load in the process of simulation-optimization and uncertainty analysis. First, the groundwater numerical simulation model was established, calibrated and verified in the northeast of Hetao Plain. Second, two surrogate models of simulation model were established using support vector regression (SVR) method, one (surrogate model A, SMA) was used to describe the corresponding relationship between the pumping rate and average groundwater table drawdown, and another (surrogate model B, SMB) was used to express the corresponding relationship between the hydrogeological parameter values and average groundwater table drawdown. Third, an optimization model was established to search an optimal groundwater exploitation scheme using the maximum total pumping rate as objective function and the limitative average groundwater table drawdown as constraint condition, the SMA was invoked by the optimization model for obtaining the optimal groundwater exploitation scheme. Finally, the SMB was invoked in the process of uncertainty analysis for assessing the reliability of optimal groundwater exploitation scheme. Results show that the relative error and root mean square error between simulation model and the two surrogate models are both less than 5%, which is a high approximation accuracy. The SVR surrogate model developed in this study could not only considerably reduce the computational load, but also maintain high computational accuracy. The optimal total pumping rate is 7947 m3/d and the reliability of optimal scheme is 40.21%. This can thus provide an effective method for identifying an optimal groundwater exploitation scheme and assessing the reliability of scheme quickly and accurately.

In this review, we show the unique potential of spleen as an optimal site for islet transplantation and a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy to treat severe diabetes mellitus, but its clinical outcome is unsatisfactory at present. One factor in clinical success of this therapy is selection of the most appropriate transplantation site. The spleen has been studied for a long time as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity. Recently it has also been shown that the spleen contributes to the regeneration of transplanted islets. The efficacy of transplantation is not as high as that obtained with intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established before the spleen can be effectively used in the clinic. Spleen also has an interesting aspect as a mesenchymal stem cell reservoir. The splenic mesenchymal stem cells contribute to tissue repair in damaged tissue, and thus, the infusion can be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

Elevated salinity is one of the major environmental limitation factors of plant growth and development and salinity stress compromises the production and survival of plantation and urban forests and agricultural crops in the arid, semi-arid, and intertidal zones. Ulmus pumila, a salt- indigenous tree species in Asia and is widely deployed in salt-affected areas in China, and U.pumila is promising for multi-varietal forestry in plantation and urban forests. The comprehensive mechanism of the intraspecific salt tolerance is still not clear yet. Here, we investigated the physiological responses of the salinity stress based on the antioxidant enzyme activities, osmotic adjustments, and gas exchange among salt-tolerant U. pumila genotypes for 100 days under five different NaCl levels (0%, 0.3%, 0.5%, 0.7%, and 0.9% w/v) with natural surroundings and rain shade at age-2. Salt stress decreased height (HR), ground diameter (DR), and dry weight (biomass) were significantly different among genotypes. HR and performance indices were positively correlated with photosynthesis rate (Pn), apparent mesophyll conductance (AMC), and chlorophyll (CHLL) with (r= 0.7 - 0.8 ***), but were negatively related to the free proline, sugar, and protein accumulation (r=-0.5 ~ -0.7***). We found that high accumulation of sugars and more activities of SOD enzyme in leaf tissue contribute to the osmotic adjustment and ROS scavenging system under salinity treatment; the sugar content and SOD activity play key roles in U. pumila’s tolerance to salt stress, and are promising indicators for U. pumila species ex vitro selections. The ex vitro selection results align with the previous in vitro studies [37] and is promising for the MVF development.

The effect of four soil-applied sulfur [S; 100 mg S kg-1 soil (100S) and 200 mg S kg-1 soil (200S)] in different sources (elemental S, ammonium sulfate, gypsum or magnesium sulfate) in protecting mustard (Brassica juncea L. Czern & Coss.) from cadmium effects was studied. Based on the observed reduction in growth and photosynthesis in plants subjected to 100 and 200 mg Cd kg-1 soil, B. juncea cv. Giriraj was selected as the most Cd-tolerant among five cultivars (namely, Giriraj, RH-0749, Pusa Agrani, RH-406, and Pusa Tarak). Sulfur applied to soil mitigated the negative impact of Cd on sulfur assimilation, cell viability and photosynthetic functions, with a lower lipid peroxidation, electrolyte leakage, and contents of reactive oxygen species (ROS: hydrogen peroxide, H2O2, and superoxide anion, O2•−). Generally, added S caused a higher activity of antioxidant enzymes (ascorbate peroxidase, catalase and superoxide dismutase), and contents of ascorbate (AsA) and reduced glutathione (GSH), and increases in the activities of their regenerating enzymes (dehydroascorbate reductase and GSH reductase), as well as rises in S assimilation, biosynthesis of non-protein thiols (NPTs) and phytochelatins (PCs). Compared to the other S-sources tested, elemental S more prominently protected B. juncea cv. Giriraj against Cd-impacts by minimizing Cd-accumulation and its root-to-shoot translocation; decreasing cellular ROS and membrane damage, and improving Cd-chelation (NPTs and PCs), so strengthening the defense machinery against Cd. The results suggest the use of elemental S for favoring the growth and development of cultivated plants also in Cd-contaminated agricultural soils.

Leptin is the archetypal adipokine that promotes a negative whole-body energy balance largely through its action on brain leptin receptors. As such, the sustained weight loss and food intake suppression induced by Roux-en-Y gastric bypass (RYGB) surgery have been attributed to enhancement of leptin receptor signalling. We formally revisited this idea in Zucker Fatty fa/fa rats, an established genetic model of leptin receptor deficiency, and carefully compared their body weight, food intake and oral glucose tolerance after RYGB with that of sham-operated fa/fa (obese) and sham-operated fa/+ (lean) rats. We found that RYGB rats sustainably lost body weight, which converged with that of lean rats and was 25.5 % lower than that of obese rats by the end of the 4 week study period. Correspondingly, daily food intake of RYGB rats was similar to that of lean rats from the second postoperative week, while it was always at least 33.9 % lower than that of obese rats. Further, oral glucose tolerance of RYGB rats was normalized at the forth postoperative week. These findings assert that leptin is not an essential mediator of the sustained weight loss and food intake suppression as well as the improved glycemic control induced by RYGB, and instead point to additional circulating and/or neural factors.

Drought events are predicted to become more prevalent in the future. Evaluating the performance of herbicide-resistant and susceptible weed ecotypes to progressive drought can provide insights into whether resistance trait(s) increased or reduced the fitness of a resistant population. Two experiments were conducted in the greenhouse between January and May 2021 to evaluate drought tolerance differences between Palmer amaranth accessions resistant to S-metolachlor or glyphosate and their susceptible counterparts. The accessions used were: S-metolachlor-resistant (17TUN-A), a susceptible standard (09CRW-A), and glyphosate-resistant (22 to 165 EPSPS copies) and glyphosate-susceptible (3 to 10 EPSPS copies) plants from accession 16CRW-D. Daily transpiration of each plant was measured. The daily transpiration rate was converted to normalized transpiration ratio (NTR) using a double-normalization procedure. The daily soil water content was expressed as a fraction of transpirable soil water (FTSW). The threshold FTSW (FTSWcr), after which NTR decreases linearly, was estimated using a two-segment linear regression analysis. The data showed differences between S-metolachlor- resistant and -susceptible accessions (P ≤ 0.05). The FTSW remaining in the soil at the breakpoint for the S-metolachlor-susceptible accession (09CRW-A) was 0.17±0.007. The FTSW remaining in the soil at the breakpoint for the S-metolachlor-resistant accession (17TUN-A) was 0.23±0.004. Although the mechanism endowing resistance to S-metolachlor might have contributed to increased drought tolerance, follow-up experiments are needed to verify this finding. Increased EPSPS copy number did not improve drought tolerance of Palmer amaranth.

The objective of this study were to conduct association mapping for drought tolerance at the seedling stage and yield-related traits. 60 cowpea accessions were used in the study. Single-nucleotide polymorphisms (SNPs) discovered through genotyping by sequencing (GBS) were used for genotyping. Association mapping was conducted using single-marker regression (SMR) in Q Gene, and general linear model (GLM) and mixed linear model (MLM) built in TASSEL. The population of the cowpea accessions were analysed using STRUCTURE 2.3.4 and the peak of delta K in the greenhouse showed seven population types, whereas the peak of delta K in the glasshouse indicated the presence of six population types. One SNP marker, 14083649|F|0-9 was associated with NP with a p value <0.001. Fifty SNP markers were associated with PWT at p <0.001. Four SNP markers, 14074781|F|0-16, 100047392|F|0-36, 14083801|F|0-28 and 100051488|F|0-49 were associated with AVSPD at p <0.001. SNP markers, 14074781|F|0-16, 14083801|F|0-28 and 100051488|F|0-49 were associated with PL at P <0.001. Five SNP markers, 100047392|F|0-36, 14083801|F|0-28, 100072738|F|0-34, 14076881|F|0-49 and 14076881|F|0-49 were associated with PWDTH at p <0.001. The 65 SNP markers identified can be used in cowpea molecular breeding to select for AVSPD, NP, PL, PWDTH, PWT, and RR through marker assisted selection (MAS).

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases, and psychiatric disorders. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants, and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses, and chronic diseases. KYN, kynurenic acid, xanthurenic acid, and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2, 3-oxygenases, and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines, and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia, and autism spectrum disorder.

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is an herbal medicine that has many potential pharmacological effects. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3,4-pentamethoxyflavone (PMF) and 5,7,4-trimethoxylfavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. The results of pharmacokinetics study revealed that only TMF and PMF, but not DMF levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The Cmax, AUC and Tmax values of PMF and TMF estimated for the 180 mg/day dose were 85.3711.31, 73.2329.93 mg/ml; 291.8948.23, 412.20203.69 mg.h/ml; and 3.890.37, 4.500.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers in a phase I study in drug development. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.

Uncertainty is the main source of risk of geological hazards in tunnel engineering. Uncertainty information not only affects the accuracy of evaluation results, but also affects the reliability of decision-making schemes. Therefore, it is necessary to evaluate and control the impact of uncertainty on risk. In this study, the problems in existing entropy-hazard model such as inefficient decision-making and failure of decision-making are analysed, and an improved uncertainty evaluation and control process are proposed. Then the tolerance cost, the key factor in the decision-making model, is also discussed. It is considered that the amount of change in risk value (R1) can better reflect the psychological behaviour of decision-makers. Thirdly, common attribute decision models, such as the expected utility-entropy model, are analysed, and then the viewpoint of different types of decision-making issues that require different decision methods is proposed. The well-known Allais paradox is explained by the proposed methods. Finally, the engineering application results show that the uncertainty control idea proposed here is accurate and effective. This research indicates a direction for further research into uncertainty, and risk control, issues affecting underground engineering works.

A radical, albeit pragmatic protocol for experimental access to putative String/M-theoretic, Einstein Unified Field Mechanical (UFM) additional dimensionality (XD) of the brane-bouquet bulk is presented. If successful, results demonstrate the existence dimensionality beyond the metric of observed physical reality provided by the Standard Model (SM) of particle physics and Cosmology. Quantum Mechanics (QM), as well-known is incomplete and further, should no longer be considered the basement of reality; meaning, Locality and Unitarity – the fundaments of quantum theory are an insufficient basis for extending the representation of reality. A seminal model of Tight Bound States (TBS) below the lowest Bohr orbit in the hydrogen atom, proposed by Vigier, is extended to a Kaluza-Klein-like (KK) cyclical tier of XD hyperspherical cavities defined within a manifold of uncertainty (MOU) of finite radius up to the semi-quantum limit, predicting, within its domain, new spectral lines in Hydrogen. The proposed protocol for this process, with phase modifications, provides efficacy of large-scale additional dimensionality (LSXD) of the brane bulk; XD-LSXD incursion duality accesses nonlocal Einsteinian UFM phenomena, leading to myriad new classes of technological innovation.

The incorporation of wind generation introduces challenges to the operation of the power system due to its uncertain characteristics. Therefore, the development of methods to accurately model the uncertainty is necessary. In this paper, the spatio-temporal Kriging and analog approaches are used to forecast wind power generation and used as input to solve an economic dispatch problem, considering the uncertainties of wind generation. Spatio-temporal Kriging takes into account the spatial and temporal information given by the database to enhance wind forecasts. We evaluate the performance of using the spatio-temporal Kriging, and comparisons are carried out versus other approaches in the framework of the economic power dispatch problem, for which simulations are developed on the modified IEEE 3-bus and IEEE 24-bus test systems. The results show that the use of Kriging-based spatio-temporal models in the context of economic power dispatch can provide an opportunity for lower operating costs in the presence of uncertainty when compared to other approaches.

We survey the main results emerging in the rapidly developing field that considers the geometry of thermodynamics and statistical mechanics. Our ideas of stability depend on variational principles – Maximum Entropy together with Least Action (and the isomorphic Least Exertion) – and this stability (invariance in time) indicates the centrality of the geometries of the systems. We explore a variety of examples of the application of thermodynamics in both macro- and micro-systems, and propose that irreversibility is an intrinsic and fundamental property of the physical realm (instead of being merely emergent). Using the concept of complex time, we examine the underlying mathematical unity of quantum mechanics, statistical mechanics, and geometrical thermodynamics. We show how the Planck and Boltzmann constants provide the fundamental quantum units for the phenomenological characteristics of the two Noether-conserved quantities controlling overall thermodynamic behaviour: respectively, energy and entropy production. We discuss the far-reaching isomorphisms (between all of complex time, temperature and the system symmetry) that always exist for Maximum Entropy systems, even as they exhibit either irreversible (dissipative, yet still dynamically stable) or reversible (including stable and static geometries) behaviours.

The purpose of this paper is to evaluate the timing of innovative investment in technology product life cycles using a compound binomial option with management flexibility. Considering the business cycles changes in the macroeconomic will affect consumer purchasing power. The focus is how to evaluate the optimal investment strategy and the project value. It was applied to different product stages (three stages including production innovation, manufacture innovation, and operation innovation) and factored to different risks to build a technology innovation strategy model. An aim of this study is the options premium of the best strategy timing for each innovation stage. Its application of the compound binomial options for the manufacture innovation will only be considered after the execution of the production innovation. The same condition is applied to the operation innovation, which will only be considered after the execution of the manufacture innovation. Then, this paper constructs the dynamic investment sequential decision model, assesses the feasibility of an investment strategy, and makes a decision on the appropriate project value and options premium for each stage under the possible change of Gross Domestic Product (GDP). This paper investigates the product life cycle innovation investment topic by using the compound binomial options method and will provide a more flexible strategy decision compared with other trend forecast criteria.

While the foundations of climate science and ethics are well established, fine-grained climate predictions, as well as policy-decisions, are beset with uncertainties. This chapter maps climate uncertainties and classifies them as to their ground, extent and location. A typology of uncertainty is presented, centered along the axes of scientific and moral uncertainty. This typology is illustrated with paradigmatic examples of uncertainty in climate science, climate ethics and climate economics. Subsequently, the chapter discusses the IPCC’s preferred way of representing uncertainties and evaluates its strengths and weaknesses from a risk management perspective. Three general strategies for decision-makers to cope with climate uncertainty are outlined, the usefulness of which largely depends on whether or not decision-makers find themselves in a context of deep uncertainty. The chapter concludes by offering two recommendations to ease the work of policymakers, faced with the various uncertainties engrained in climate discourse.

Maize (Zea mays subsp. mays) is the staple food crop in the world. In this study, multi-layer perceptron (MLP), support vector machine (SVM), genetic algorithm-based multi-layer perceptron (MLP-GA), and genetic algorithm-based support vector machine (SVM-GA) hybrid artificial intelligence algorithms were used for the prediction of drought tolerance and stress tolerance indices in teosinte maize lines. Correspondingly, the gamma test technique was applied to determine efficient input and output vectors. The potential of developed models was evaluated based on statistical indices and graphical representation. Results of gamma test based on the least value of gamma and standard error indices show that day of anthesis (DOA), day of silking (DOS), yield index (YI), and gross yield per plant (GYP) information vector arrangements were determined as efficient information vector combination for drought-tolerant index (DTI) as well as the stress-tolerant index (STI). The results of MLP, SVM, MLP-GA, and SVM-GA algorithms were compared based on statistical indices and visual interpretation that have satisfactory for prediction of the drought-tolerant index and stress-tolerant index in maize crop. It has also seemed that genetic algorithm-based hybrid models (MLP-GA and SVM-GA) were found a better prediction of the drought-tolerant index and stress-tolerant index in maize crop. Similarly, the SVM-GA model has the highest potential to forecast the DTI and STI in maize crops as compared to MLP, SVM, MLP-GA models.

An attractive option for realizing applications in radiation environments is to employ All-Programmable System-on-Chips (APSoCs) thanks to their high-performance computing and power efficiency merits. Despite APSoC's advantages, like any other electronic device, they are prone to radiation effects. Processors found in APSoCs must, therefore, be adequately hardened against ionizing-radiation to become a viable alternative for harsh environments. This paper proposes a novel triple-core lockstep (TCLS) approach to secure the Xilinx Zynq-7000 APSoC dual-core ARM Cortex-A9 processor against radiation-induced soft errors by coupling it with a MicroBlaze TMR subsystem in Zynq's programmable logic (PL) layer. The proposed strategy uses software-level checkpointing principles along with roll-back and roll-forward mechanisms (i.e. software redundancy), and hardware-level processor replication as well as checker circuits (i.e. hardware redundancy). Results of fault injection experiments show that the proposed solution achieved high soft error security by mitigating about 99% of bit-flips injected into both ARM cores' register data.

For more than eighty years the standard interpretation (SI) has dominated quantum physics. Perspectives that have tried to challenge this domination have been remarkably unsuccessful. As a result, quantum theory (QT) has remained remarkably stagnant. The article offers a critical examination of SI and provides an explanation for its continued domination. It also uses Bohmian mechanics—a theoretical perspective advanced by American physicist David Bohm—as a case study for why alternative interpretations have failed to displace SI. The article sees the main reason for the failure to achieve much progress beyond SI in the unresolved philosophical problem of subject-object relation that continues to plague our study of physics. The article sketches a path to a possible solution and outlines a new science practice that this solution will require.

Biostimulants are materials that when applied in small amounts are capable of promoting plant growth. Nanoparticles (NPs) and nanomaterials (NMs) can be considered as biostimulants since, in specific ranges of concentration, generally in small levels, they increase the plant growth. Pristine NPs and NMS have a high density of surface charges capable of unspecific interactions with the surface charges of the cell walls and membranes of plant cells. In the same way, the functionalized NPs and NMS, and the NPs and NMs with a corona formed after the exposition to natural fluids such as water, soil solution, or the interior of organisms, presents a high density of surface charges that interact with specific charged groups in cell surfaces. The magnitude of the interaction will depend on the materials adhered to the corona, but the high-density charges located in a small volume causes an intense interaction capable of disturbing the density of surface charges of cell walls and membranes. The electrostatic disturbance can have an impact on the electrical potentials of the outer and inner surfaces, as well as on the transmembrane electrical potential, modifying the activity of the integral proteins of the membranes. The extension of the cellular response can range from biostimulation to cell death and will depend on the concentration, size, and the characteristics of the corona.

Based on a previous risk calculation study along a road corridor, risk is recalculated using stochastic simulation by introducing variability for most of the parameters in the risk equation. This leads to an exceedance curve comparable to that of catastrophe models. This approach introduces uncertainty into the risk calculation in a simple way, which can be used for poorly documented cases to fulfil lack of data. This approach seems to tend to minimize risk or to question risk calculations.

Inositol transporter (INT) is reputed as the pivotal transporter for vital metabolites like lipids, minerals, and sugars particularly. These transporters play important role in transitional metabolism and various signaling pathways in plants through regulating the transduction of messages from hormones, neurotransmitters, and immunologic and growth factors. Extensive studies have been conducted on animal INT with promising outcomes. However, few recent studies have highlighted the importance and the complexity of INT genes in the regulation of plant physiology stages including growth and tolerance to stress conditions. The present review sum-up the most recent findings on the role of INT or inositol genes in plant metabolisms and the responsive mechanisms that cope with external stressors. Moreover, we highlighted the emerging role of vacuoles and vacuolar inositol transporters in plant molecular transition and their related roles in plant growth and development. Inositol transporters are the essential mediator for the inositol uptake and its intracellular broadcasting for various metabolic pathways where they play crucial roles. Also, so far characterized only in animals, we reported evidence on Na+/inositol transporters H+/inositol symporters and suggested their roles and operating mode in plants. Thus, understanding the INT functioning system, the coordinated movement of inositol, and the relation between inositol generation and other important plant signaling pathways would be an excellent asset for advancement in researches on plant stress adaptation.

Pv11, an insect cell line established from the midge Polypedilum vanderplanki, is capable of ametabolic desiccation tolerance, so-called anhydrobiosis. We previously discovered that heat shock factor 1 (HSF1) contributes to the acquisition of desiccation tolerance by Pv11 cells, but the mechanistic details have yet to be elucidated. Here, by analyzing the gene expression profiles of newly established HSF1-knockout and -rescue cell lines, we show that HSF1 has a genome-wide effect on gene regulation in Pv11. HSF1-knockout cells exhibit a reduced desiccation survival rate, but this is completely restored in HSF1-rescue cells. By comparing mRNA profiles of the two cell lines, we reveal that HSF1 induces anhydrobiosis-related genes, especially genes encoding late embryogenesis abundant proteins and thioredoxins, but represses a group of genes involved in basal cellular processes, thus promoting an ametabolic state in the cell. In addition, HSF1 binding motifs are enriched in the promoters of anhydrobiosis-related genes and we demonstrate binding of HSF1 to these promoters by ChIP-qPCR. Thus, HSF1 directly regulates the transcription of anhydrobiosis-related genes and consequently plays a pivotal role in the induction of anhydrobiotic ability in Pv11 cells.

Surrogate model based optimization method is widely-used to accelerate the design and optimization process~\cite{marler2004survey}. The input of regression model used in the surrogate model are numbers, which requires users to parametrize the geometries. In this paper, a new parameterization-free surrogate model is introduced and its corresponding uncertainty quantification and sensitivity analysis method are discussed. The input of new surrogate model methods is surface mesh of simulation domain. \Gls{gnns} is used to extract geometric information, and \Gls{cnns} is used to predict contours. This framework bypasses parameterization,as a consequence, uncertainties introduced by manual parameterization is reduced. However, such changes compared with conventional surrogate model methods impose great challenge on uncertainties quantification and sensitivity analysis. Uncertainties quantification in this paper means the error bar of prediction results, which is calculated by Gaussian Process Regression method in current surrogate method. In this paper, a new quantification method achieved by Kullback-Leibler divergence (KLD) is introduced. And the sensitivity analysis is conducted by Automatic Differentiation, which gives a Jacobian matrix of inputs. The method and analysis mentioned above are demonstrated by a low-pressure steam turbine rotator and its exhaust system.

Upland cotton is sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D), and the identification of potentially 2,4-D tolerant cotton chromosome substitution (CS) lines and understanding tolerance mechanisms provide a significant step into the development and genetic improvement of upland cotton to reduce yield loss caused by 2,4-D herbicide effects including the drifts. Experiments were conducted to understand the possible mechanism of herbicide tolerance in CS-T04-15, CS-T07, and CS-B15sh, 2,4-D herbicide-tolerant cotton CS lines compared with TM-1, the 2,4-D herbicide susceptible recurrent parent of the CS line as control, using [14C]2,4-D. Percent absorption rate and translocation patterns of the 14C-labeled herbicide application at 5.17 kBq at 6 to 48 hours after treatment (HAT) were determined. The tolerant cotton CS lines showed 15-19% [14C]2,4-D uptake while TM-1 exhibited a reduced uptake of only 1.4% [14C]2,4-D at 24 HAT. Distribution of the absorbed [14C]2,4-D showed that 2-5% was translocated outside the treated leaf. In TM-1, 77% of the herbicide was translocated above and below the treated leaf, contrasting with the reduced translocation of 14C-labeled herbicide observed in the tolerant CS lines. Interestingly, CS-T04-15 showed a restricted movement of 14C below the treated leaf at 6 to 48 HAT, suggesting a novel mechanism of herbicide tolerance. This finding is the first report on upland cotton demonstrating a complex differential uptake and translocation associated with herbicide tolerance for [14C]2,4-D in cotton CS lines.

Methods to handle uncertainty in economic evaluation have gained much attention in the literature and the cost-effectiveness acceptability curve (CEAC) is the most widely used method to summarize and present uncertainty associated with program costs and effects in cost-effectiveness analysis. Some researchers have emphasized the limitations of the CEAC for informing decision and policy makers as the CEAC is insensitive to radial shifts of the joint distribution of incremental costs and effects in the North-East and South-West quadrants of the cost-effective plane (CEP). Furthermore, it has been pointed out that the CEAC does not incorporate risk-aversion in valuing uncertain costs and effects. In the present article we show that the cost-effectiveness affordability curve (CEAFC) captures both dimensions of the joint distribution of incremental costs and effects on the CEP and is therefore sensitive to radial shifts of the joint distribution on the CEP. Furthermore, the CEAFC also informs about the budget impact of a new intervention as it estimates the joint probability an intervention is both affordable and cost-effective. Moreover, we show that the cost-effectiveness risk-aversion curve (CERAC) allows to incorporate risk-aversion into the analysis and can therefore be used to inform decision-makers who are risk-averse. We use data from a published cost-effectiveness model of palbociclib in addition to letrozole versus letrozole alone for the treatment of oestrogen-receptor positive, HER-2 negative, advanced breast cancer to demonstrate the differences between CEAC, CEAFC and CERAC and show how these can jointly be used to inform decision and policy makers.

Creating new business models is crucial for the implementation of clean technologies for industrial decarbonization. With incomplete knowledge of market processes and uncertain conditions, assessing the prospects of a technology-based business model is challenging. This study combines business model innovation, system dynamics and exploratory model analysis to identify new business opportunities in a context of socio-technical transition and assess their prospects through simulation experiments. Furthermore, insights are visualized in a roadmap to coordinate action among the actors involved. This combination of methods is applied to the case of a business model aiming at ensuring stability of the electrical grid by centralizing the management of flexible loads in industrial companies. A system dynamics model was set up to simulate the diffusion of flexible electrification technologies. Through scenario definition and sensitivity analysis, the influence of internal and external factors on diffusion was assessed. Results highlight the central role of energy costs and customer perception. The chosen combination of methods allowed the formulation of concrete recommendation for coordinated action, explicitly accounting for the various sources of uncertainty. We suggest testing this approach in further business model innovation contexts.

Understanding the mechanism for heat tolerance is important for the hot pepper breeding program to develop heat-tolerant cultivars in changing climate. This study was conducted to investigate physiological and biochemical parameters related to heat tolerance and to determine leaf heat damage levels critical for selecting heat-tolerant genotypes. Seedlings of two commercial cultivars, heat-tolerant ‘NW Bigarim’ (NB) and susceptible ‘Chyung Yang’ (CY), were grown in 42 °C for ten days. Photosynthesis, electrolyte conductivity, proline content were measured among seedlings during heat treatment. Photosynthetic rate was significantly reduced in ‘CY’ but not in ‘NB’ seedlings in 42 °C. Stomatal conductivity and transpiration rate was significantly higher in ‘NB’ than ‘CY’. Proline content was also significantly higher in ‘NB’. After heat treatment, leaf heat damages were determined as 0, 25, 50 and 75% and plants with different leaf heat damages were moved to a glasshouse (30–32/22–24 °C in day/night). The growth and developmental parameters were investigated until 70 days. ‘NB’ was significantly affected by leaf heat damages only in fruit yield while ‘CY’ was in fruit set, number and yield. ‘NB’ showed fast recovery after heat stress compared to ‘CY’. These results suggest that constant photosynthetic rate via increased transpiration rate as well as high proline content in heat stress condition confer faster recovery from heat damage of heat-tolerant cultivars in seedlings stages.

Background: Pre-treatment with lipopolysaccharide (LPS) protected the kidney against a later lethal ischemia. To reveal the mechanisms of renal cross-tolerance and septic acute kidney injury we investigated the effects of LPS on miRNA expression in the kidney. Methods: Male NMRI mice were injected with 40 and 10 mg/kg LPS ip. and sacrificed at 1.5 and 6 hours (early preconditioning, EP) and at 24 and 48 hours (late preconditioning, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Results: Plasma urea concentration peaked at 24 hours after LPS and decreased thereafter. Renal TNF-α and IL-6 mRNA were extremely elevated at all time-points. miRNome changes were mild at 1.5 hours, most miRNAs were altered at 6 and 24 hours and declined by 48 hours. Not all miRNAs could be assayed or validated by qPCR. In EP miR-762 was newly identified and validated and was the most elevated miRNA with both methods. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p and miR-146a-5p. MiR-21a-3p increased significantly in both EP and LP. Conclusion: miR-762 might attenuate the LPS-induced immune response during EP and the miR-144/451 cluster is involved in LPS-induced renal preconditioning.

Leishmania species are parasitic protozoans which cause leishmaniasis affecting millions of people worldwide. Sterols are important components of plasma and organellar membranes and serve as precursors for the synthesis of signaling molecules. In contrast to animals, Leishmania do not produce cholesterol but instead synthesize ergostane-based sterols. C14-demethylase is a key enzyme involved in the biosynthesis of sterols in Leishmania parasites and an important drug target. Its inactivation leads to multiple defects including increased plasma membrane fluidity, mitochondrion dysfunction, hypersensitivity to stress and reduced virulence. In this study, we revealed a novel role for sterol synthesis in the maintenance of RNA stability and translation. Sterol alteration in C14-demethylase knockout mutant leads to increased RNA degradation, reduced translation and impaired heat shock response. Thus, sterol biosynthesis plays an unexpected role in global gene regulation in Leishmania parasites.