Good health and the promotion of well-being for all is the third of the 17 Global Goals included in the 2030 Agenda for Sustainable Development. Contributing to this goal, the current study aimed to examine the relationships between one kind of athletes’ well-being, namely state organic self-talk, with personality traits, and basic psychological need satisfaction and frustration within their sport. Athletes (N = 691; mean age 21.65) from a variety of individual (n = 270) and team sports (n = 421) completed a multisection questionnaire capturing the targeted variables. Three-step hierarchical regression analyses revealed that: In step 1, all personality traits were to some extent a significant predictor of athletes’ organic, spontaneous self-talk dimensions and goal-directed self-talk functions. In step 2, need satisfaction significantly contributed to all spontaneous self-talk dimensions and goal-directed self-talk functions (except for creating functional deactivated states) over and above personality. Finally, in step 3, need frustration significantly contributed to negative spontaneous self-talk dimensions, and to all goal-directed self-talk functions (except for instruction) over and above personality and need satisfaction. Overall, our results indicate the importance of personality traits as personal antecedents, and perceptions of basic psychological need satisfaction and frustration as social-environmental antecedents, in shaping athletes’ state organic self-talk.

Organizational skills are a set of cognitive abilities responsible for goal-directed behaviors. While they are moderately studied in clinical settings, the assessment of organizational skills in the general population remains under-studied. This paper presents the new Durand Organizational Skills Questionnaire (DOSQ), which was developed to examine the factors associated with organizational abilities in the general population. Exploratory factor analysis, validated by a confirmatory factor analysis, suggests eight factors: Work Organization, Communication Clarity, Punctuality, Goal-Oriented Behavior, Assiduity, Workspace Organization, Strategies, and Attentiveness. Three studies using samples from the general population provided evidence for the reliability and validity of the DOSQ’s scores. Overall, the results suggest that the DOSQ offers a valid approach to measuring organizational skills in the general population.

The research proposes a self-directed paradigm with self-design using the existing technology with LMS modules, discussions, and self-tests. The research establishes its criteria for assurance of teaching and learning known as 7x2C for the compliance of content, and appearance along with other criteria for the analysis. The above technology of web and LMS is tested for a business course that is technology-oriented in creating an experiential learning system for Covid-19 awareness. Similarly, among other ideas, an environment for educating learners about diabetes and obesity has been designed. The project is known as Sunchoke with its theme of Grow, Eat, and Heal. The educators can use their technology and apply self-directed pedagogy to transform this approach to their customized ways by using their content and rubrics.

This article assumes that collaborators who adopt a positive-sum, prosocial perspective can build trust-based relationships, which is equivalent to collaborative ability (CA). To improve a collaborator’s CA, we anticipated that content based upon a model of positive-sum collaboration, founded upon ancestral behaviours presented as social norms, might alter a zero-sum, proself, collaborator’s perspective. However, we also postulated that learner’s willingness to engage in positive-sum content may rely on pre-existing prosociality. Intervention participant’s prosociality was assessed via self-assessment of their emotional intelligence (EQ), quality of life (QoL), and goal orientation (GO). Learner’s engagement in online content was assessed by the three stage reached: examine website front matter; examine website content; learn website content. Tukey’s multiple comparison showed a statistically significant difference between stages one and three, in the mean of respondent’s self-assessed QoL. This suggests that participants who wished to learn content had, on average, higher quality of life, and potentially therefore greater prosociality. In general, these findings support a claim that any intervention designed to increase individual prosociality may need to consider the target population’s reticence to engage.

Citizen science substantially contributes to large-scale biodiversity monitoring and the enhancement of public literacy. While both of the contributions largely depend on the public’s self- regulated learning. In this study, we employed a mix- method approach, incorporating both a questionnaire survey of 133 participants and interviews with 12 volunteers, aiming to explore the feature of self- regulated learning in citizen science, as well as identify the main factors impacting it. The volunteers are all different ages, from different jobs, with varying educational backgrounds. The findings revealed that the educational background of volunteers did not significantly impact their self-regulated learning. However, an increased frequency of participation was linked to higher levels of self-regulated learning. Furthermore, achievement goal orientation mediates the prediction of self-regulation by scientific epistemology. These insights underscore the importance of enhancing citizen science's impact on scientific literacy by fostering self-regulated learning among participants. This can be achieved through explicit instruction in scientific epistemology and by fostering a sense of achievement to boost achievement goal orientations. Additionally, our study advocates for the promotion of social interaction between students and out- of- school citizen scientists in school-based citizen science projects. The main innovation of this study is to consider volunteers as learners, not merely as contributors of data.

Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.

The contemporary landscape of education is witnessing a paradigm shift towards innovative instructional methods, with the flipped learning approach gaining considerable attention. The purpose of this research was to investigate the impact of the flipped learning approach on students' perception and acceptance throughout an entire semester in the 'Introduction to Programming with Java' course, using a research design with a quantitative approach, ultimately aiming to inform educational practice and advance our knowledge of innovative teaching methods in higher education. This study was conducted at a university with 174 students involved, divided into two groups, 87 students in the experimental group and 87 students in the control group. The data collected through the scales were analyzed by using descriptive and inferential statistical analysis techniques in statistical software. At the end of the measurements, the technology acceptance level and self-directed learning perceptions of engineering students who received education with flipped learning were high. The results suggest that educators should consider students' readiness for self-directed learning when implementing the flipped learning approach and focus on creating an environment that supports their autonomy and engagement. This research offers valuable guidance for instructors, curriculum designers, and educational policymakers seeking to enhance the effectiveness of flipped learning in higher education courses.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

Since the end of 2019 and throughout 2020 the world has been devastated by the SARS COVID-19 pandemic. The sport world suddenly had to deal with a massive reorganization of events with important implications on the physical and psychological preparation of athletes and coaches. The purpose of this study was to explore how these changes impacted coaches’ and athletes’ goal setting strategies and their experience of goal adjustment. As part of a wider mixed-method project involving 2162 coaches and 1354 athletes, an online qualitative survey was used, and data collected were analyzed using reflexive thematic analysis. Findings highlighted three overarching themes, in response to goal adjustment: “Moving on toward new goals”, “Letting go of goals”, and “Trying to hold on”, with several themes and sub-themes identifying different nuances of athletes’ and coaches’ experience. The implications of such findings for the mental preparation of high-level athletes are discussed in two ways. Firstly, in light of existing literature on goal setting from an applied perspective; secondly, in the broader perspective of the sport culture and the application of our themes to other challenging moments that sport professionals might encounter.

The study sought to investigate the effect of Multi-choice Goal programming in project Portfolio Analysis, using Lagos State Project Portfolio from between 2017-2021 as a study case. Specifically, the objectives examined the effectiveness of multi-choice goal programming in analyzing the project Portfolio of Lagos State Government and investigated the possible lapses in the use of Multi-choice Goal programming in analyzing the project Portfolio of Lagos State Government. Data were gathered from the State financial Statements and analyzed using Lingo-17 Software. Based on the analysis, the study discovered that the goals formulated can be optimally and minimally attained as the positive deviational and negative deviational variables depict zero. This indicates that the cost incurred on the project portfolio was absolutely minimized during the period and at the same time; Lagos State Government derived the most preferred benefits from it. The study therefore concluded that the State minimized the project costs and at the same time maximized benefits while meeting its overall objectives.

Background: Coronavirus disease (COVID-19) has caused one of the worst global pandemics in recent decades. It has disrupted education systems worldwide, leading to a forced shift from traditional face-to-face to blended or fully distanced learning, requiring a higher level of student readiness for self-directed learning (SDL) and a more internal locus of control (LOC). Objective: This study explored the relationship between locus of control and level of readiness for SDL among Saudi nursing students and whether the COVID-19 pandemic has impacted this relation-ship. Methods: a cross-sectional correlational descriptive study was conducted to survey 277 Saudi nursing students enrolled in the bachelor program at one of the reputable universities in Saudi Arabia. An E-questionnaire containing two scales, the Self-Directed Learning Readiness Scale for Nursing Education, and the Locus of Control Scale, was used to collect data in addition to the selected participants’ characteristics. Results: Nursing students had a moderate-to-low level of readiness for SDL (mean = 144.0), and the majority had an external LOC. There was a significant association between the locus of control and level of readiness for self-directed learning (r = 0.19*, p = 0.001), and the internal locus of control was more significantly associated with self-directed learning (r = 0.22*, p = 0.0001) than with external locus of control. Conclusion: The study findings indicate a propensity of respondents towards an external locus of control, whereas most of the respondents’ reported levels of readiness ranged between low and moderate across all dimensions of self-directed learning. This study was not registered.

Using Directed Transfer Function (DTF) and Partial Directed Coherence (PDC) in their information version, this paper extends their theoretical framework to incorporate instantaneous Granger Causality (iGC)’s frequency domain description into a single unified perspective. We show that standard vector autoregressive models allow portraying iGC’s repercussions associated with Granger Connectivity where interactions mediated without delay between time series can be easily detected.

Negative mental health in students currently is classified as a global crisis with the highest and lowest student achievers recognized at greatest risk. Public schooling, in reproducing accepted psychosocial beliefs through standardized learning, developed separately from necessitating student mental health, in contrast to self-directed learning. Differing from standardized learning, the objective of self-directed learning in public schools is the creation of relevant support structures for student mental health, promoting positive psychosocial outcomes. The designed separation of public schooling from both mental health and self-directed learning was first acknowledged—and lamented—by John Dewey, over 100 years ago, in anticipating today’s mental health crisis. Yet, in responding effectively to the limitations of COVID-19, self-directed learning became an acknowledged learning method in public schools, potentially able to be accommodated by them regularly in support of mental health through the use of online technology. This study investigates the COVID-19 results of self-directed online learning in public schools through a Google Scholar search of peer reviewed research regarding self-directed learning, online learning, and mental health during COVID-19, recommending support for self-initiated self-directed online learning so that self-directed learning can continue, post COVID-19, improving student mental health in public schools, leading to positive psychosocial outcomes.

We present a new computing package Flagser, designed to construct the directed flag complex of a finite directed graph, and compute persistent homology for flexibly defined filtrations on the graph and the resulting complex. The persistent homology computation part of Flagser is based on the program Ripser [2], but is optimised specifically for large computations. The construction of the directed flag complex is done in a way that allows easy parallelisation by arbitrarily many cores. Flagser also has the option of working with undirected graphs. For homology computations Flagser has an Approximate option, which shortens compute time with remarkable accuracy. We demonstrate the power of Flagser by applying it to the construction of the directed flag complex of digital reconstructions of brain microcircuitry by the Blue Brain Project and several other examples. In some instances we perform computation of homology. For a more complete performance analysis, we also apply Flagser to some other data collections. In all cases the hardware used in the computation, the use of memory and the compute time are recorded.

Digital technology makes energy systems more dynamic, efficient, reliable and sustainable. Promoting the digital governance of renewable energy is not only a key part of energy transformation, but also an important initiative to cope with the global energy crisis, which provides a new impetus for realizing the goal of net-zero emissions. In order to achieve the "dual-carbon" goal, China has been actively promoting energy reform and enhancing the wide application of digital technologies in the development and utilization of renewable energy. The digital governance system and governance capacity of renewable energy is an important support for the modernization of the national governance system and governance capacity. Although the digital governance of renewable energy in China has better policy support and advantages, the dilemmas it faces are still relatively prominent, including unsound laws and policies, insufficient governance capacity, and security loopholes in digital technology, etc. Therefore, this paper proposes a problem-oriented approach to the digital governance of renewable energy. Therefore, this paper puts forward problem-oriented optimization suggestions to innovate the legal system of renewable energy digital governance, promote the digital transformation of China's renewable energy industry, provide development space for renewable energy digital governance in a diversified mode, and enhance the digital governance capacity by improving the renewable energy security system.

Good health and well-being is one of the essential SDGs that ensure healthy lives and promote well-being for all ages and further entails providing substantial medical services to the public at low cost and with minimal adverse effects on the environment. Information and communication technologies (ICTs) have taken on an increasingly important function as significant facilitators of healthcare reform, with the goals of enhancing access to health services, the quality of treatment provided, and the overall productivity of the healthcare system. However, the integration of ever-increasing ICT technologies into the healthcare systems, also referred to as digital transformation, is not a straightforward process, but it comes with different types of challenges from integration level to application design level and security level. Although several studies have been proposed to address the integration of ICT technologies into healthcare systems, there is still a need for a comprehensive research study on the integration and design challenges, security and privacy challenges, application areas, and possible positive and negative impacts. Therefore, this paper contributes as the research literature study covering an important SDG, "Good health and well-being," and its digital transformation, along with summarising our research findings in a detailed and taxonomical way. To start with, firstly, we present a detailed comparison of existing studies on healthcare and well-being, mainly focusing on integrating ICT technologies in healthcare in terms of sustainable aspects, security and privacy challenges, design and integration challenges, E-health-related applications, and future directions. We also present an overview and the need for digital transformation in healthcare, discuss its significant components, highlight E-health's importance and benefits, explore its integration and design challenges, and categorise the security and privacy challenges. Next, we present an in-depth discussion on the role of Blockchain technology as today's leading technology in E-health, discussing Blockchain technology and its characteristics, highlighting its benefits, and describing the possible types of Blockchain-based E-health use cases. Furthermore, we discuss the positive and negative impact of ICT integration along with identifying open issues and challenges of integrating ICT technologies into the healthcare systems and discuss future research directions, which provide the strength for researchers to address the issues in future solutions.

In a previous paper we defined the Black-and-White SAT problem which has exactly two solutions, where each variable is either true or false. We showed that Black-and-White $2$-SAT problems represent strongly connected directed graphs. We presented also the strong model of communication graphs. In this work we introduce two new models, the weak model, and the Balatonbogl\'{a}r model of communication graphs. A communication graph is a directed graph, where no self loops are allowed. In this work we show that the weak model of a strongly connected communication graph is a Black-and-White SAT problem. We prove a powerful theorem, the so called Transitions Theorem. This theorem states that for any model which is between the strong and the weak model, we have that this model represents strongly connected communication graphs as Blask-and-White SAT problems. We show that the Balatonbogl\'{a}r model is between the strong and the weak model, and it generates $3$-SAT problems, so the Balatonbogl\'{a}r model represents strongly connected communication graphs as Black-and-White $3$-SAT problems. Our motivation to study these models is the following: The strong model generates a $2$-SAT problem from the input directed graph, so it does not give us a deep insight how to convert a general SAT problem into a directed graph. The weak model generates huge models, because it represents all cycles, even non-simple cycles, of the input directed graph. We need something between them to gain more experience. From the Balatonbogl\'{a}r model we learned that it is enough to have a subset of a clause, which represents a cycle in the weak model, to make the Balatonbogl\'{a}r model more compact. We still do not know how to represent a SAT problem as a directed graph, but this work gives a strong link between two prominent fields of formal methods: SAT problem and directed graphs.

The airport ground handling service (AGHS) equipment vendor selection (AGHSEVS) problem is critical for ramp work safety management, because AGHS equipment malfunctions affect airport ramp work safety. Appropriate vendor selection can prevent aircraft damage and delays in airlines schedules, and ensure reliable and high-quality ground handling service. The AGHSEVS problem is a time-consuming and complex process that requires professional knowledge and experience to make judgments. Specifically, AGHSEVS is a multi-criteria decision-making (MCDM) problem. Previous research has seldom integrated MCDM methods with linear and goal programming to solve the AGHSEVS problem. The objective of this study was to develop a new system evaluation model for AGHSEVS by considering both qualitative and quantitative methods. We test the proposed approach on an AGHS company in Taiwan.

This letter attempts to find splashing height of liquid-filled container drop impact to a solid surface by dimensional analysis (DA). Two solutions were obtained by both traditional DA and directed DA without solving any governing equations. It is found that the directed DA can provide much more useful information than the traditional one. This study shows that the central controlling parameter is called splash number $\mathrm{Sp}=\mathrm{Ga} \mathrm{La}^\beta=(\frac{gR^3}{\nu^2})(\frac{\sigma R}{\rho \nu^2})^\beta$, which is the collective performance of each quantity. The splash height is given by $ \frac{h}{H}=(\frac{\rho\nu^2}{\sigma R})^\alpha f[\frac{gR^3}{\nu^2}(\frac{R\sigma}{\rho\nu^2})^\beta]=\frac{1}{\mathrm{La}^\alpha}f(\mathrm{Ga}\cdot \mathrm{La}^\beta)$. From the physics of the splashing number, we can have a fair good picture on the physics of the liquid splashing as follows: the jets propagation will generate vortex streets from the container bottom due to sudden pressure increasing from drop impact (water-hammer effect), which will travel along the container sidewall to the centre of the container and subsequently excite a gravity wave on the liquid surface. The interaction between the gravitational force, surface force and viscous force is responsible for creating droplet splash at the liquid surface.

Zika virus (ZIKV), a mosquito-borne flavivirus, was an almost neglected pathogen until its introduction in the Americas in 2015, where it has been responsible for a threat to global health, causing a great social and sanitary alarm due to its increased virulence, rapid spread, and an association with severe neurological and ophthalmological complications. Currently, no specific antiviral therapy against ZIKV is available, and treatments are palliative and mainly directed to symptoms relief, such as fever and rash, by administering antipyretics, anti-histamines, and fluids for dehydration. Nevertheless, lately, a great effort has been made to search for antiviral candidates using different approaches and methodologies, ranging from repurposing of specific compounds with known antiviral activity to the screening of libraries and of natural compounds. The identified antiviral candidates include drugs targeting viral components (structural proteins and enzymes), as well as cellular ones. Here, we present an updated review of current knowledge about anti-ZIKV strategies, focusing on host-directed antivirals as a realistic alternative to combat ZIKV infection.

Viruses with spindle or lemon-shaped virions are rare in the world of viruses, but are common in viruses of archaeal extremophiles, possibly due to the extreme conditions in which they thrive. However, the structural and genetic basis for the unique spindle shape is unknown. The best-studied spindle-shaped virus, SSV1, is composed mostly of the major capsid protein VP1. Similar to many other viruses, proteolytic cleavage of VP1 is thought to be critical for virion formation. Unlike half of the genes in SSV1, including the minor capsid protein gene vp3, the vp1 gene does not tolerate deletion or transposon insertion. In order determine the role of the vp1 gene and its proteolysis for virus function, we developed techniques for site-directed mutagenesis of the SSV1 genome and complemented deletion mutants with vp1 genes from other SSVs. By analyzing these mutants we demonstrate that the N-terminus of the VP1 protein is required, but the N-terminus, or entire SSV1 VP1 protein, can be exchanged with VP1s from other SSVs. However, the conserved glutamate at the cleavage site is not essential for infectivity. Interestingly, viruses containing point mutations at this position generate mostly abnormal virions.

In 2010, Parties to the Convention on Biological Diversity (CBD) adopted the Strategic Plan for Biodiversity 2011–2020 to address the loss and degradation of nature. Subsequently, almost all biodiversity indicators have continued to decline. Nevertheless, it is well established that conservation actions can make significant positive differences for species and ecosystems. Therefore, the Post-2020 Global Biodiversity Framework, which is currently being developed, has immense potential to motivate efforts to ‘bend the curve’ of biodiversity loss. Here we contend that Goal B on species, as articulated in the Zero Draft of the Post-2020 Framework, is inadequate for preventing extinctions, and ambiguous regarding reversing population declines, both of which are required to achieve the CBD’s proposed 2030 mission “to put biodiversity on a path to recovery for the benefit of planet and people”. We examine the limitations of the current wording of the goal and propose an articulation with a robust scientific basis. A global goal for species that strives to end extinctions and recover populations of all threatened and depleted species can help align actors towards the transformative actions and interventions needed to allow humans to live in harmony with nature.

Extraversion, a Big Five personality trait, has been identified as a significant factor in COVID-19 positive coping—yet, relevant research is conflicting. Studies have not situated the influence of extraversion within a geographical and historical context. Thus, a sound base is lacking for assessing when opposing results regarding extraversion and COVID-19 positive coping are likely to result. Furthermore, extraversion with respect to COVID-19 coping has not been considered concerning other-directed learning in contrast to self-directed learning. To establish a sufficiently sound base, an examination of the range of high-ranking Google Scholar results on extraversion and COVID-19 coping from different countries during the pandemic’s various waves—pre and post vaccine introduction—is undertaken. The same are then considered for insights into public opinion. Following, extraversion is compared with other-directed learning and differentiated from self-directed learning. An understanding is thus presented for assessing when extraversion will necessarily be an effective personality trait for COVID-19 positive coping and when it will not. Extraversion’s effect will be found inherently inconsistent for identifying COVID-19 positive coping as a result, because of its dependence on other-directed learning. The conclusion: COVID-19 positive coping stability is contingent on personal values that guide self-directed learning, rather than other-directed extraversion.

This study introduces a novel computational approach for testing conditional independence (BB CI test) within causal Directed Acyclic Graphs (DAGs), leveraging Bayesian non-parametric bootstrap and machine learning techniques. Our method offers an alternative for validating the assumptions underpinning causal DAGs. Through simulation studies and an industrial case analysis, we demonstrate the test procedure in accurately assessing conditional independence, comparing it with the Generalized Covariance Measure (GCM) test. Our findings suggest that the BB CI test is advantageous in scenarios where existing methods may falter due to violations of model assumptions. This research contributes to the causal inference literature by providing a computational tool for researchers and practitioners to validate causal models.

The Collatz conjecture is a well-known number theory puzzle that states that every positive integer would eventually converge to the trivial cycle of 1, 2, 1, 2,... when repeatedly exposed to a particular transformation. In this transformation, even numbers are divided in half, odd numbers are tripled, and one is added. In this study, we present a new method for creating a directed graph and using it to display and analyze Collatz sequences. Our technique creates what we call a Collatz directed graph by joining an endless number of simple directed graphs, each of which corresponds to a natural number. We show by careful mathematical analysis that all positive integers are included in this Collatz directed graph. Moreover, we give an evidence that verifies the Collatz conjecture by showing that the sole cycle in this graph is the trivial cycle of 1, 2, 1, 2,... We also prove that there is no sequence that diverges to infinity in this graph. Our results provide insights into the fundamental structure of Collatz sequences and further our knowledge of the Collatz conjecture .

This paper provides an overview of modelling and simulation methods for complex systems, including queuing and life support systems. To realize and capture every aspect of a system or situation, a model is used in place of the actual one. Using a model and simulation, we may create scenarios and make decisions. Computer experiments with the model can save costs, time, and effort once its validity has been shown. A model of the thing under study is created by computer simulation, which then runs the model on a digital computer and examines the results. It's interesting to note that a knowledge base of data includes information about predicted behaviour of the model as well as coordinated determination of external variables and parameters. Selecting the precise model creation technique is the first and most difficult task in simulation. A review of techniques used in simulation model execution (serial and parallel discrete-event simulation), simulation model analysis (calibration, validation, verification, goal-seeking), and conceptual, declarative, functional, constraint, and multimodal design are presented in this paper.

The Sustainable Development Goals (SDGs) represent a central framework to guide sustainable urban development (2030 Agenda). However, it is not clear how and where SDG 11 (Sustainable Cities and Communities) is being implemented, and how such implementation might be improved. We investigated this subject by analyzing United Nations (UN) SDG Good Practices data from 2018 to 2021. We applied five criteria to the 336 SDG 11 responses: (1) geography; (2) actors; (3) progress toward targets; (4) areas of implementation; and (5) scale of action. Overall, 86 of the 193 countries that adopted the 2030 Agenda submitted at least one SDG 11 good practice. 33 countries contributed 73.8% of the total, and most developing countries did not make submissions. A very small number of responses (between 2.6 and 9.1%) addressed equity-related targets. Good practices from developed countries were usually more technology-based and system-forming; developing countries typically focused on issues of day-to-day concern. Overall, this analysis points to the need for better and more systematic reporting on SDG 11 implementation, a more active public sector role in SDG implementation and reporting, more focus on dimensions related to social equity, and better formulation of urban sustainability targets and indicators in the future.

Prostate cancer lung metastasis represents a clinical conundrum due to their implication of advanced disease progression and the complexities they introduce in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, the review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, the review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Catheter-based revascularization procedures developed as an alternative of systemic thrombolysis for patients at intermediate-high and high-risk pulmonary embolism. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow up. Secondary endpoints were short- and mid-term changes in echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high risk PE (86%), mostly female (57%), median age 66.5 years (IQR 56-74), and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 hours and at follow up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74) while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, oh whom 4.9% were BARC 3. Preliminary results from USAT IH-PE registry showed low incidence of PH, improvement in RV function and a safe profile.

Routing a person through a traffic network presents a tension between selecting a fixed route that is easy to navigate and selecting an aggressively adaptive route that minimizes the expected travel time. We propose to create non-aggressive adaptive routes in the middle-ground seeking the best of both these extremes. Specifically, these routes still adapt to changing traffic conditions, however we limit the number of adjustments made in the route. This improves the user experience, by providing a continuum of options between saving travel time and minimizing navigation. We design strategies to model single and multiple route adjustments, and investigate enumerative techniques to solve these models. To alleviate the intractability with handling real-life traffic data, we develop efficient algorithms with easily computable lower and upper bounds. We finally present computational experiments highlighting the benefits of limited adaptability in terms of reducing the expected travel time.

Re-shaping of thermodynamics with the graph theory and Ramsey theory is suggested. Maps built of thermodynamic states are addressed. Thermodynamic states may be attainable and non-attainable by the thermodynamic process in the system of constant mass. We address the following question how large should be a graph describing connections between discrete thermodynamic states to guarantee the appearance of thermodynamic cycles? The Ramsey theory supplies the answer to this question. Direct graphs emerging from the chains of irreversible thermodynamic processes are considered. In any complete directed graph, representing the thermodynamic states of the system the Hamiltonian path is found. Transitive thermodynamic tournaments are addressed. The entire transitive thermodynamic tournament built of irreversible processes does not contain a cycle of length 3, or in other words, the transitive thermodynamic tournament is acyclic and contains no directed thermodynamic cycles.

For any positive integer n ≥ 2, the Erdős-Straus Conjecture claims that the Diophantine equation 4/n = 1/x + 1/y + 1/z has a solution where x, y, z are also positive integers. In this paper, a directed network based on this equation is generated, with properties such as its average clustering coefficient, average path length, degree distributions, and largest strongly connected component analysed to reveal some underlying trends about the nature of the conjecture. Potential connections between different numbers, that result from satisfying a source-solution relationship for this equation, are described using the appropriate number-theoretic interpretations wherever possible, while conjectures backed by these trends are made in other instances. Additionally, a directed configuration model is used to show that the origin of several results is the degree sequence of the network. Metrics relating to the prime number nodes, specifically their in and out degrees, are also explored to yield some intriguing observations. On the whole, the aim is to highlight the viability of complex networks as a computational tool to study this general class of problems pertaining to fixed-length unit fraction splits.

High-frequency neuroelectric signals like electroencephalography (EEG) or magnetoencephalography (MEG) provide a unique opportunity to infer causal relationships between local activity of brain areas. While causal inference is commonly performed through Classical Granger causality (GC) based on multivariate autoregressive models, this method may encounter important limitations (e.g. data paucity) in the case of high dimensional data from densely connected systems like the brain. Additionally, physiological signals often present long-range dependencies which commonly require high autoregressive model orders / number of parameters. We present a generalization of autoregressive models for GC estimation based on Wiener-Volterra decompositions with Laguerre polynomials as basis functions. In this basis, the introduction of only one additional global parameter allows to capture arbitrary long dependencies without increasing model order, hence retaining model simplicity, linearity and ease of parameters estimation. We validate our method in synthetic data generated from families of complex, densely connected networks and demonstrate superior performance as compared to classical GC. Additionally, we apply our framework to studying the directed human brain connectome through MEG data from 89 subjects drawn from the Human Connectome Project (HCP) database, showing that it is able to reproduce current knowledge as well as to uncover previously unknown directed influences between cortical and limbic brain regions.

In this comprehensive review, we delve into the realm of intention recognition within the context of digital forensics and cybercrime. The rise of cybercrime has become a major concern for individuals, organizations, and governments worldwide. Digital forensics is a field that deals with the investigation and analysis of digital evidence in order to identify, preserve, and analyze information that can be used as evidence in a court of law. Whereas, Intention recognition is a subfield of artificial intelligence that deals with the identification of agents’ intentions based on their actions and change of states. In the context of cybercrime, intention recognition can be used to identify the intentions of cybercriminals and even to predict their future actions. Employing a meticulous six-step systematic review approach, we curated research articles from reputable journals and categorized them into three distinct modeling approaches: logic-based, classical machine learning-based, and deep learning-based. Notably, intention recognition has transcended its historical confinement to network security, now addressing critical challenges across various subdomains, including social engineering attacks, AI black box vulnerabilities, and physical security. While deep learning emerges as the dominant paradigm, its inherent lack of transparency poses unique challenges in the digital forensics landscape. We advocate for hybrid solutions that blend deep learning’s power with interpretability. Furthermore, we propose the creation of a comprehensive taxonomy to precisely define intention recognition, paving the way for future advancements in this pivotal field.

A significant body of research has examined the accuracy and diversity of several types of recommendation systems. However, little is known about the psychological mechanisms underlying the effects of the different types of recommendation systems on user satisfaction. The findings of our experiment showed that user satisfaction is influenced by shopping goal. Specifically, when a user’s shopping goal aligns with the type of recommendation system, the user satisfaction is enhanced. Our study evaluated the mediating role of feeling right and psychological reactance for a better understanding of this relationship. We further tested the moderated mediation effect of feeling right and psychological reactance moderated by the user shopping goal. For goal-directed users, accurate recommendations trigger the activation of feeling right, consequently increasing the user satisfaction. Conversely, when exploratory users face accurate recommendations, they activate psychological reactance, which leads to a reduction in user satisfaction.

Due to a shortage of funding and other market challenges, Small and Medium-sized Enterprises (SMEs) have a tough time adopting new technologies. Numerous technological obstacles nega-tively impact the long-term commercial achievement of SMEs. The deployment of Industry 4.0 might resolve several technological challenges. A sustainable city is a difficult structure whose economical, societal, and ecological components interact and compete with one another. There is a dearth of actual methodologies for measuring interaction. The objective of Industry 4.0 is to obtain a better degree of performance effectiveness and profitability, and greater automation. Conse-quently, the purpose of the research is to determine the influence of Industry 4.0 in fostering economic efficiency in small and medium enterprises' sustainability. A Sustainable City using Multi-Criteria Decision Making (SC-MCDM) system is designed in this research to test and achieve sustainable developmental goals. This paper then gives a technique for calculating the interaction between various standards, such as static interactions and dynamical pattern resemblance, as well as the weight variables of every indication generated by the connection. Furthermore, the ap-plication of the suggested technique is proved by assessing the sustainable development goals of twelve Chinese cities within the Triple Bottom Line (TBL) paradigm. From a geographic-temporal viewpoint, spatial variations in city sustainability reveal regional inequalities in sustainability. Indicator scores suggest that the lack of research spending, falling financing in stationary assets, shortage of financial development, and inadequate shared transit are the most significant limiting factors for most communities. Furthermore, the growth of tertiary industries, the improvement of energy performance, the expansion of green areas, and the reduction of pollution emissions are the key driving forces for enhancing sustainability. Compared to other methodologies, Multi-Criteria Decision Making (MCDM) considers the interplay between conditions, which is an excellent way to assess the sustainability of a city. The experimental findings show the impact of MCDM and sustainability to achieve sustainable development goals.

The 2030 Agenda for Sustainable Development, the SDGs, are high on the agenda for most countries of the world. In its publication of the SDGs, the UN has provided the goals and target descriptions that, if implemented at a country level, would lead towards a sustainable future. The IAEG (InterAgency Expert Group of the SDGs) was tasked with disseminating indicators and methods to countries that can be used to gather data describing the global progress towards sustainability. However 2030 Agenda leaves it to countries to adopt the targets with each government setting its own national targets guided by the global level of ambition but taking into account national circumstances. At present, guidance on how to go about this is scant, but it is clear that the responsibility is with countries to implement and that it is actions at a country level that will determine the success of the SDGs. SDG reporting by countries takes on two forms 1) global reporting using prescribed indicator methods and data; 2) National Voluntary Reviews where a country reports on its own progress in more detail but is also able to present data that are more appropriate for the country. For the latter, countries need to be able to adapt the global indicators to fit national priorities and context, thus the global description of an indicator could be reduced to describe only what is relevant to the country. Countries may also, for the National Voluntary Review, use indicators that are unique to the country but nevertheless contribute to measurement of progress towards the global SDG target. Importantly, for those indicators that relate to the security of natural resources security (e.g. water) indicators, there are no prescribed numerical targets/standards or benchmarks. Rather countries will need to set their own benchmarks or standards against which performance can be evaluated. This paper presents a procedure that would enable a country to describe national targets with associated benchmarks that are appropriate for the country. The procedure focusses on those SDG targets that are natural resource-security focussed e.g. extent of water-related ecosystems (6.6), desertification (15.3) etc., because the selection of indicator methods and benchmarks is based on the location of natural resources, their use and present state and how they fit into national strategies.

Genetic diversity is the foundation of evolutionary resilience, adaptive potential, and the flourishing vitality of living organisms, serving as the cornerstone for robust ecosystems and the continuous evolution of life on Earth. The landscape of directed evolution, a powerful biotechnological tool inspired by natural evolutionary processes, has undergone a transformative shift propelled by innovative strategies for generating genetic diversity. This shift is fuelled by several factors, encompassing the utilization of advanced toolkits like CRISPR-Cas and base editors, enhanced comprehension of biological mechanisms, cost-effective custom oligo pool synthesis, and the seamless integration of artificial intelligence and automation. This comprehensive review looks into the myriad methodologies employed for constructing gene libraries, both in vitro and in vivo, categorized into three major classes: random mutagenesis, focused mutagenesis, and DNA recombination. The objectives of this review are threefold: firstly, to present a panoramic overview of recent advances in genetic diversity creation, secondly, to inspire novel ideas for further innovation in the genetic diversity generation, and thirdly, to provide a valuable resource for individuals entering the field of directed evolution.

Defects in low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. Defective LDLR in hepatocytes leads to increased blood cholesterol level that damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully comprehended. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSC) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-EC), we detected the LDLR protein predominantly in its mature form, while iPSC-EC from patients with FH display reduced level of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of iPSC-EC with mutant LDLR revealed a unique transcriptome profile comprising downregulated genes related to monocarboxylic acid transport, exocytosis and cell adhesion, as well as upregulated signaling pathways of cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increases susceptibility of endothelial cells to inflammation and oxidative stress. This, combined with elevated extrinsic cholesterol levels, may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies related to FH.

The term new genomic techniques (NGTs), is an umbrella term to describe a variety of techniques that can alter the genetic material of an organism and that have emerged or have been developed since 2001, when the existing genetically modified organism (GMO) legislation was adopted. The analytical framework to detect GMOs in Europe is a established single harmonized procedure which is mandatory for authorization of GM food and feed, thus generating reliable, transparent and effective labelling scheme for GMO products. However, NGT products challenge the implementation and enforcement of the current regulatory system in the EU, relating in particular to the detection of NGT products that contain no foreign genetic material. Consequently, current detection methods will fail to meet minimum performance requirements. Although existing detection methods may be able to detect and quantify even small alterations in the genome, this does not necessarily confirm the distinction between products resulting from NGTs subject to the GMO legislation and other products. Therefore, this study provides a stepwise approach for the in silico prediction of PCR systems specificity by testing a bioinformatics pipeline for amplicon and primer set searches in current genomic databases. We have tested our methodology in two mutant genotypes produced by CRISPR/Cas9 in Arabidopsis thaliana. Overall, our results demonstrated that the single PCR system developed for the identification of a nucleotide insertion in the grf1-3 genotype has sufficient hits in the databases that would not allow discrimination of this mutanted event. Differently, the second mutated genotype grf8-61 which contains a -3bp deletion, found no matches in the sequence variant database. Our approach is the first step in decision making on PCR system and modification of them for empirical testings.

Directed acyclic graphs (DAGs) are nonparametric causal path diagrams that have substantial utility as principled representations of disease and healthcare pathways, and of the underlying ‘data generating mechanisms’ these pathways involve. As such, DAGs provide a valuable bridge between: the aetiological knowledge, operational insight and professional experience on which clinical training and practice depend; and the more abstract epistemological and analytical considerations required to extract robust statistical insight from health and healthcare data. DAGs are nonetheless vulnerable to imperfect biomedical paradigms, partial clinical knowledge and limited empirical data. DAGs drawn under such circumstances offer limited scope for statistical insight free from cognitive, analytical or inferential bias if: they misrepresent the data generating mechanisms involved; or ignore the important role that omitted variables (whether measured, unmeasured or unacknowledged) might play therein. To address these weaknesses and broaden the appeal and application of DAGs, this chapter provides ten simple steps that educators can use to improve the analytical competence and statistical confidence of the healthcare students, qualified practitioners and experienced researchers they support. These steps use temporal logic to draw DAGs so as to: reduce reliance on uncertain knowledge, incomplete information, flawed assumptions or guesswork; and avoid, mitigate or acknowledge the errors and biases that each of these incur. The chapter comprises an accessible, non-technical overview of the perspective and thoughtfulness required to generate temporally coherent DAGs as objective representations of the probabilistic causal paths involved in context-specific data generating mechanisms. It encourages a focus on those variables operating as potential sources of analytical or inferential bias when estimating the plausible, probabilistic causal relationship between two pre-specified variables; and specifically addresses the challenges posed by: omitted; time-variant; non-asynchronous; and temporally obscure variables. The chapter includes a worked example based on a published clinical study to demonstrate how each of the steps required to generate temporally-informed DAGs can be applied to: critically appraise the analytical decisions made during applied healthcare research; and inform the decisions required when designing, undertaking and analysing primary and secondary, prospective and retrospective research. The appendices include a summary of ten recommendations for improving the reporting and interrogability of DAGs and DAG-informed analyses.

The origins of directed acyclic graphs (DAGs) date back to the emergence of ‘graph theory’ in the early 1700s (Biggs et al. 1986). DAGs are conceptual or literal, diagrammatic representations of causal paths between variables which are constructed – as their name suggests – on the basis of two over-riding principles: first, that all causal paths are ‘directed’ (i.e. for each pair of variables, only one can represent the cause, while the other must be its consequence); and second, that no direct cyclical paths, or indirect cyclical pathways (comprising sequences of consecutive paths) are allowed, such that no consequence can be considered its own direct or indirect cause (hence ‘acyclic’; Law et al., 2012). As such DAGs reflect the knowledge, presumptions, assumptions and/or speculation of the analyst(s) concerned regarding the causal relationships between each of the variables included therein. Current convention dictates that variables are represented as nodes/vertices, and that any causal paths between variables are represented as directed arcs/edges/lines, often in the form of arrows (see Figure 1). Although each arc indicates the presence and direction of a known/presumed/assumed/speculative causal relationship between the two variables concerned, drawing an arc does not require the sign, magnitude, precision or shape of the relationship to be known or declared (Tennant et al., 2021). In this respect, DAGs provide a simple, uncomplicated, accessible and entirely nonparametric approach for postulating causal relationships amongst any variables of interest even when these are uncertain, unknown or entirely speculative (Ellison, 2020). Nonetheless, as a result of the parametric constraints imposed by the presence/absence of possible arcs within any given DAG, these also reflect and support a number of more sophisticated statistical applications which make it possible to use DAGs to inform the design of multivariable statistical models that reflect the causal structure(s) involved – albeit without the need to know or understand the mathematical technicalities on which these are based (Lewis and Kuerbis, 2016). These features make DAGs attractive cognitive, educational and analytical tools for strengthening the epistemological, theoretical and empirical basis of causal inference, and there has been a recent proliferation in the use of DAGs across a range of applied scientific disciplines (e.g. Knight and Winship, 2013), and an associated upsurge in analytical methods training (e.g. Elwert, 2011; Gilthorpe, 2017; Hernán 2018; Roy, 2021; Hünermund, 2021). This Chapter reflects on a decade of delivering medical statistics training to undergraduate medical students at the University of Leeds between 2012-2021 in which the third year research, evaluation and special studies module (‘RESS3’) has used DAGs to support the development of applied statistical skills relevant to the extended student-selected research and evaluation projects (ESREP) students undertake in their fourth and final years (Ellison, 2021; Ellison et al., 2014a,b). Based on successive iterations of the structure and content of the RESS3 module, together with notes made during formal and informal planning and review meetings with module leads, lecturers, tutors and students, we draw on the claims and criticisms made of DAGs in the epidemiological literature to identify a number of explicit strengths (and associated, often implicit. weaknesses) that are central to their use in prediction and causal inference modelling. While using DAGs requires (and benefits from) a clear understanding of their non-parametric nature and parametric implications, the weaknesses of DAGs seem likely to reflect both: the challenges inherent in the modelling of data generating processes when these are imperfectly understood; and troublesome cognitive and heuristic tendencies common to all analytical tools – in which the tool facilitates the task in hand by reducing the necessity (and benefits of) exploring uncertainties and identifying assumptions. These, more epistemological considerations appear particularly challenging for medical undergraduates to grasp (Ellison, 2021), but also appear poorly understood by many established analysts and clinical epidemiologists (Ellison, 2020).

Directed energy deposition (DED) is an efficient method to fabricate functionally graded materials (FGMs) with gradient composition and complex structures, allowing for local tailoring of properties instead of the costly need for extraneous welds and joints. In this study, a FGM from stainless steel to Inconel alloy was successfully fabricated using the powder-based laser DED. A very refined grain structure has been observed in at the composition with 75 wt.% Inconel alloy content, which also exhibits the highest (entropy). For the first time, the post heat treatments, microstructure and aging precipitation behaviors of FGMs were systematically studied via experimental characterization and computation, to elucidate their effects on the gradient smoothing and mechanical properties. The diffusion and segregation of Ni, Nb and Ti elements underly the transformation mechanism between Laves, δ, γ’ and γ’’ phases during precipitation. Homogenization on FGMs not only eliminates the heterogeneity inherited from the AM process, but also provides a practical way to smoothen the gradient on composition and microstructure for the eventual good gradient properties. It has a direct influence on the following precipitation behaviors in the FGM, which highly relies on the diffusion degree of the elements in the matrix and grain boundaries. The high-throughput thermodynamic modeling and kinetic modeling were exploited to evaluate the experimental microstructure and address computational uncertainty using different thermodynamic conditions and databases, which enables an accelerated design through local tailoring of process-structure-property relationships to develop new functional materials.

Background: High coronary thrombus burden has been associated with unfavorable outcomes in patients with ST-segment elevation myocardial infarction (STEMI), the optimal management of which has not yet to be established. Methods: We evaluated the safety and efficacy of adjunctive catheter-directed thrombolysis (CDT) during primary percutaneous coronary intervention (PCI) in patients with STEMI and high thrombus burden. Results: Among the 1,849 consecutive patients with STEMI, 263 had high thrombus burden. Moreover, 41 patients received intracoronary infusion of tissue plasminogen activator during primary PCI (CDT group), whereas 222 did not receive (non-CDT group). No significant differences in bleeding complications and in-hospital and long-term mortalities were observed (9.8% vs. 7.2%, p=0.53; 7.3% vs. 2.3%, p=0.11; and 12.6% vs. 17.5%, p=0.84, CDT vs. non-CDT). In patients who underwent antecedent aspiration thrombectomy during PCI (75.6%; CDT group and 87.4%; non-CDT group), thrombolysis in myocardial infarction grade 2 or 3 flow rate after thrombectomy was significantly lower in the CDT group than in the non-CDT group (32.2% vs. 61.0%, p&lt;0.01). However, the final rates improved considerably without significant difference (90.3% vs. 97.4%, p=0.14). Conclusions: For STEMI patients with high thrombus burden, adjunctive CDT is safe and effective for improving coronary flow. CDT resulted in favorable coronary flow even after unsatisfactory aspiration thrombectomy.

Genetic switches can be utilized for many purposes in synthetic biology including the assembly of complex genetic circuits to achieve sophisticated cellular systems and the construction of biosensors for real-time monitoring of intracellular metabolite concentrations. Although genetic switches have mainly been developed in prokaryotes to date, eukaryotic genetic switches are increasingly being reported as both rational and irrational engineering technologies mature. In this review, we describe genetic switches in yeast based on synthetic transcription factors and/or synthetic promoters. We also discuss directed evolution technologies for the rapid and robust construction of yeast genetic switches.

Complex systems can be described as the network of interactions between their components. In directed networks, information, energy and matter flow in dominant directions. Undirected networks, on the other hand, cannot easily capture these asymmetries. The local flow of information depends on the node spin, which is a function of the number of incoming and outgoing links attached to it. And yet, how the heterogeneous association between in-degree and out-degree constraints global dynamics remains poorly understood. Here, we develop a new theoretical model to study the relationship between node directionality and global flow dynamics. Our computational analysis of random and scale-free directed networks indicates that structural diversity constrains the dimensionality of reachable dynamical space. These results suggest how local directionality might be an universal driver of global dynamics in many systems, from social networks, to technological systems to the connectome.

The purpose of this study was to evaluate the implementation level of urban Sustainable Development Goals (SDGs) in the Republic of Korea and to measure the extent of internal and external impacts on the implementation level. An evaluation framework was established based on relative efficiency theory, and the implementation level of urban SDGs at the local government unit in the Republic of Korea was examined by performing an analysis of each stage. First, in reference to the 2018 cross-section, the implementation level of target 11.2 (public transportation) was assessed as excellent across the country, compared with the implementation level of targets 11.5 (disaster safety), 11.6 (environment), and 11.7 (public space), which were assessed as needing improvement. Second, the factors positively impacting the implementation level of target 11.2 were urban population, GRDP, financial independence, urbanization area, and bus-only lanes, whereas the factors positively impacting the implementation level of target 11.5 were population density and GRDP. The positive factors influencing the implementation level of target 11.6 (air quality sector) were found to be GRDP, financial independence, administrative area, and renewable energy generation, whereas the effective factors of the implementation level of target 11.6 (waste management sector) were analyzed as GRDP, financial independence, and the population density of households in the waste management area. The positive factors influencing the implementation level of target 11.7 were GRDP, financial independence, administrative area, and green area.

Both academic literature and global organizations have emphasized the need for responsible water consumption, as stated in the Sustainable Development Goal 12. However, individuals’ water-saving behaviors in their current state are not enough. This situation entails a resistance to change (RC) in consumer habits and a lack of perceived risk of scarcity. The novelty of this study lies in examining the influence of RC (through its emotional, cognitive, and confidence components) and perceived risk on water-saving intention. Interviews (n = 384) were conducted in the southeast Mediterranean area of Spain by interviewers using a paper-and-pencil questionnaire. The results of the structural equation modeling show that the perceived risk and the components of cognitive rigidity and negative emotions exert a direct influence on water-saving habits and an indirect influence on water-saving intention. None of the components of RC directly influence intention, and a lack of confidence in the outcomes of water saving does not influence water-saving habits or water-saving intention. In addition to the results obtained, the novelty of the work lies in the idea that in order to influence the perception of the risk of water scarcity through awareness campaigns, it is better to use an emotional message rather than showing facts or information, because this does not drive water saving behavior.

Accessing energy in the world is crucial nowadays. Energy is an essential factor to achieve other SDGs including SDG7. However, the determination and evaluation of the relationship between different energy scenarios to achieve SDG 7 and other SDGs have not done yet. This paper seeks to fill this gap by investigating how energy seniors can contribute to achieving SDG 7 and other SDGs. Web of Science, ScienceDirect and Scopus databases were utilized for conduction a systematic review. A total finial 25 from 249 papers were filtered from 2015 to December 2020 via inclusion and exclusion criteria. This review involves six seniors of energy which primary linked to achieving the SDG 7 and other SDGs: modern energy 20% (n = 5/25), energy access 16% (n = 4/20), energy efficiency 8% (n= 2/16), renewable energy 28% (n= 7/14), energy services 8% (n= 2/7), and miscellaneous energy 20% (n= 5/5). This systematic review explores the opportunities, constraints and limitations, recommendations, and new directions. The results show that different energy scenarios contribute to achieving mainly (SDG7) and other SDGs. The outcomes from this systematic review provide a sense of direction for future researchers for future studies in this domain.

Using insights from cybernetics and an information-based understanding of biological systems, a precise, scientifically inspired, definition of free-will is offered and the essential requirements for an agent to possess it in principle are set out. These are: a) there must be a self to self-determine; b) there must be a non-zero probability of more than one option being enacted; c) there must be an internal means of choosing among options (which is not merely random, since randomness is not a choice). For (a) to be fulfilled, the agent of self-determination must be organisationally closed (a `Kantian whole'). For (c) to be fulfilled: d) options must be generated from an internal model of the self which can calculate future states contingent on possible responses; e) choosing among these options requires their evaluation using an internally generated goal defined on an objective function representing the overall `master function' of the agent and f) for `deep free-will', at least two nested levels of choice and goal (d-e) must be enacted by the agent. The agent must also be able to enact its choice in physical reality. The only systems known to meet all these criteria are living organisms, not just humans, but a wide range of organisms. The main impediment to free-will in present-day artificial robots, is their lack of being a Kantian whole. Consciousness does not seem to be a requirement and the minimum complexity for a free-will system may be quite low and include relatively simple life-forms that are at least able to learn.

Graph visualization has evolved significantly over time, offering various methods to effectively represent complex data structures. This study introduces a novel force-directed algorithm for 3D data visualization, specifically tailored for commonly used datasets in linked data visualization. Leveraging the power of graph theory and methods, the algorithm aims to address the challenge of creating visually appealing and easily interpretable visualizations, which often necessitate advanced user interaction. By utilizing 3D space and the Unity Engine, the research successfully visualizes data and develops interactive visualizations, overcoming limitations of basic force-directed implementations. The main contribution of presented research is in the force-directed algorithm with springs and controlled placement as a visualization technique that combines the use of springs and attractive forces to stabilize a graph in a 3D environment. The combination of these two techniques also helps prevent the formation of a single large cluster within the graph, enhancing the overall visualization quality.

The meaning of a good social outcome in land use transport policy/planning has been relatively underdeveloped, compared to economic and environmental sustainability goals, but this is now changing. Cities are increasingly prioritizing reducing social exclusion, with the allied intent of providing all residents with equitable access to the benefits of their city. However, in jurisdictions that use cost-benefit analysis to guide government decision-making, this poses a challenge: monetization of the benefits of reducing social exclusion is poorly developed. An evaluation gap thus confronts benefit-cost based assessment of initiatives intended to reduce social exclusion, compared to initiatives directed towards societal economic and environmental goals. This is a particular problem for public transport services that primarily enable people at risk of mobility-related social exclusion to access more opportunities in their society (social transit). The benefits of reducing social exclusion associated with these services have not been monetized, so social transit initiatives are poorly placed to argue their merits against competing initiatives where benefit monetization is more advanced (e.g., mass public transport and roads). The paper summarizes Australian research that has developed monetized measures for the value of increased trip making, bridging/bonding social capital, sense of community and several conceptions of wellbeing, and of reducing neighbourhood disadvantage, as these contribute to reducing social exclusion. New Singaporean research on the value of trip making to support reduced exclusion is also presented, affirming the Australian trip values. Trip values are then used in case study examples to show they can make a material difference to the societal worth of initiatives intended to reduce exclusion. Using these trip values, and other pathway values linked to reducing social exclusion, closes or at least substantially reduces the evaluation gap confronting social goal achievement in land use transport policy and planning, strengthening the case for reducing exclusion. These values will assist jurisdictions that are seeking to provide their residents with more equitable access to the benefits of their city.

The framework of product life cycle (PLC) cost analysis is one of the most important evaluation tools for a contemporary high-tech company in an increasingly competitive market environment. The PLC-purchasing strategy provides the framework for a procurement plan and examines the sourcing strategy of a firm. The marketing literature emphasizes that ongoing technological change and shortened life cycles are important elements in commercial organizations. From a strategic viewpoint, the vendor has an important position between supplier, buyer and manufacturer. The buyer seeks to procure the products from a set of vendors to take advantage of economies of scale and to exploit opportunities for strategic relationships. However, previous studies have seldom considered vendor selection (VS) based on PLC cost (VSPLCC) analysis. The purpose of this paper is to solve the VSPLCC problems considering the situation of a single-buyer-multiple-supplier. For this issue, a new VSPLCC procurement model and solution procedure are derived by this paper to minimize net cost, rejection rate, late delivery and PLC cost subject to vendor capacities and budget constraints. Moreover, a real case in Taiwan is provided to show how to solve the VSPLCC procurement problem.

Directed energy deposition (DED) parameters were determined for near-β alloy Ti-55511 by employing statistical design of experiments (DOE) methods. Parameters resulting in fully dense freeform deposits were identified using two sequential DOEs. Single laser tracks were printed with several laser power, traverse rate, and powder feed rate settings in an initial DOE to identify promising build parameters. Capture efficiency and effective deposition rate were used to characterize and rank the single track deposits. The best parameters were then used to print solid cube with various X-Y and Z-overlaps (different hatch spacing, HS, and layer thickness, ZS) in a second DOE. Suitable deposition parameters were selected based on cube density and microstructure and were used to fabricate larger tensile samples for mechanical testing. Multiple parameter sets were found to provide dense Ti-55511 deposits with acceptable mechanical properties and parametric models showed statistical significance.

The combination of wet-lab experimental data on multi-site combinatorial mutations and machine learning is an innovative method in protein engineering. In this study, we present an improved innovative sequence–activity relationship (innov'SAR) methodology based on novel descriptors and digital signal processing (DSP) to construct a predictive model. In this improved approach, 21 experimental (R)-selective amine transaminases from Aspergillus terreus (AT-ATA) were used as an input to predict higher thermostability than that predicted using the existing data. We successfully improved the determination coefficient (R2) of the model from 0.66 to 0.92. In addition, root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were estimated and conformation analysis based on molecular dynamics simulations was performed to verify the enhanced thermal stability of the screened mutants. The improved innov'SAR algorithm enhanced the predictive accuracy, suggesting a method for modifying the stability of AT-ATA, which may help in directed evolutionary screening and open up new avenues for protein engineering.

Despite of over 20 years of community directed treatment with ivermectin (CDTI), a high prevalence of onchocerciasis and onchocerciasis-associated epilepsy were observed in rural villages in Mahenge, Tanzania. Therefore, we assessed the knowledge, attitude and practice about onchocerciasis in four rural villages in the Mahenge area. This was a qualitative study conducted between June and July 2019. Eleven focus group discussions were organized with persons with epilepsy and their caretakers, community resource persons, and community drug distributors (CDDs), and two in-depth interviews with district programme coordinators of neglected tropical diseases (NTD). Most participants were aware about symptoms of onchocerciasis using local terminologies such as “ukurutu/rough dry skin” and “kuwashwa/itching”. A small proportion of people did not take ivermectin during CDTI for fear of adverse reactions such as itching and swelling. Some men believed that ivermectin may decrease libido. Challenges for high CDTI coverage included, long walking distance by CDDs to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision by the NTD coordinators. In conclusion, ivermectin uptake in Mahenge should be optimised by continuous advocacy about the importance of taking ivermectin to prevent onchocerciasis-associated morbidity and by improving supervision during CDTI.

A large variety of molecular interactions occurs between biomolecular components in cells. When one or a cascade of molecular interactions results in a regulatory effect, by one component onto a downstream component, a so-called ‘causal interaction’ takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g., gene regulation) need to be described with a careful appreciation of molecular interactions that occur between entities. A proper description of this information enables archiving, sharing, and reuse by humans and for computational science. Various representations of causal relationships between biological components are currently used in a variety of resources. Here, we propose a checklist that accommodates current representations, and call it the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while assuring uniformity and interoperability of the data across resources.

The diffusion of New Ways of Working (NWW) is an important trend in contemporary organi-zations. Many related empirical studies have been produced, but none have focused on differences in employees’ perceptions of the opportunity to use NWW according to organization sector (pri-vate, semi-public, public). This study, based on neoinstituionalism and HR attributions theory, investigated these differences via a survey (n=2693) of employees at private (n=358), semi-public (n=204), and public (n=2131) organizations. The results show that public employees reported less opportunity to use NWW than their private and semi-public counterparts. Furthermore, private sector employees were more likely to attribute well-being and productivity benefits to NWW than their public sector and semi-public counterparts. We also show that institutional and organiza-tional variables specific to the characteristics of organizations in the three sectors partially ex-plain the degree of perceptions with respect to the opportunity to use NWW.

This study has investigated the effect of nutrition labeling on consumer guilt, in situations where consumers ingest products that have an unhealthy image. The first investigation has examined the effects of types of nutrition labeling (adding healthy ingredients/reducing unhealthy ingredients). The second investigation has examined the influence of two goal-activation types(utilitarian and hedonic) and nutrition labeling on consumer guilt. The findings reveal that the utilitarian-goal-activation group felt less guilty about consuming a product with a reduced unhealthy ingredient than they did about consuming a product with an added healthy ingredient. In addition, there were interactions between the two variables, since consumer goal activation had more effect on consumer guilt about products with reduced unhealthy ingredients than on products with added healthy ingredients. Based on these results, the academic and practical implications of the present study are discussed. and proposes several directions for future research.

Today’s purchasing companies demand an advanced buyer equal of enactment from their supplier while the two parties maintain a respectful connection. Although the supplier selection (SC) product life cycle cost (SCPLCC) is an important consideration among corporations, SCPLCC problem has become associated with deciding how one supplier should be selected from possible alternatives. In this study, we applied two types of goal programming, multiobjective linear programming and revised multichoice goal programming to develop a PLCC-based concept to solve the SCPLCC problem and construct a decision-making tool for application to a case of supply chain management in a Taiwanese light-emitting diode company in the high-tech industry. Our study main contribution Company managers can easily use the two approaches of the SCPLCC model with different parameters to solve SCPLCC model problems. Finally, we comparing five models found RMCGP with weighted linear goal programming had an adequate effect for application to the PLCC concept for high-technology comapny; this cloud make company decision–makers focus on low PLCC and select better supplier.

Climate change has become the greatest threat to the survival of world and its ecosystem. With the irreversible impact on the ecosystem, problems like rise in sea level, food-insecurity, natural resources scarcity, seasonal disorders have increased over the past few years. Among these problems, the issue of water scarcity due to the lack of water resources and global warming has plagued several nations. Owing to the rising concerns over water scarcity United Nations (UN) has acknowledged water as a primary resource to the development of societies under the ‘Water Goal’ of the sustainable development goals. As the changing climate and intermittent availability of water resources pose major challenges to forecast demand, especially in countries like the United Arab Emirates (UAE) which has one of the highest per capita residential water consumption rates in the world. Therefore, the aim of this study is to propose an accurate water demand forecasting technique that incorporates all significant factors to predict the future water demands of the UAE. The forecasting model used is the Long Short Term Memory (LSTM), with the factors considered are mean temperature, mean rainfall, relative humidity, Gross Domestic Product (GDP), Consumer Price Index (CPI) and population growth. The LSTM model predicts the water demand forecasting in the UAE showing that the future demand will decrease from 1821 million m3 in 2018 to 1809.9 million m3 in 2027.

Abstract: CRISPR/Cas systems are used for genome editing, both in basic science and in bio-technology. At the same time, CRISPR/Cas editors have several limitations, including insufficient specificity leading to "off-targets" and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have been obtained now, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cere-visiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.

Cholesterol biosynthesis inhibitors (statins) protect hypercholesterolemic patients from developing active tuberculosis, suggesting that these drugs could help the host to control the pathogen at the initial stages of the disease. This work studies the effect of fluvastatin on the early response of healthy peripheral blood mononuclear cells (PBMC) to inactivated Mycobacterium tuberculosis (Mtb) H37Ra. We found that in fluvastatin-treated PBMC, most monocytes/macrophages became foamy cells that overproduce NLRP3 inflammasome components in the absence of immune stimulation, evidencing important cholesterol metabolism/immunity connections. When both fluvastatin-treated and untreated PBMC were exposed to Mtb, a subset of macrophages quickly captured large amounts of bacilli and died, concentrating the bacteria in necrotic areas. In fluvastatin-untreated cultures, most of the remaining macrophages became epithelioid cells that isolated these areas of cell death in granulomatous structures that barely produced IFN-gamma. By contrast, in fluvastatin-treated cultures, foamy macrophages surrounded the accumulated bacteria to degrade them, markedly activated caspase-1 and elicited a potent IFNgamma/cytotoxic response. In rabb-gammaits immunized with the same bacteria, fluvastatin therapy increased the tuberculin test response. We conclude that statins enhance macrophage effectiveness to control Mtb supported by adaptive immunity, offering a promising tool in the design of alternative therapies to fight tuberculosis.

Recent results have shown that the human malaria-resistant hemoglobin S mutation originates de novo more frequently in the gene and in the population where it is of adaptive significance, namely, in the hemoglobin subunit beta gene compared to the non-resistant but otherwise identical 20A>T mutation in the hemoglobin subunit delta gene, and in sub-Saharan Africans, who have been subject to intense malarial pressure for many generations, compared to Northern Europeans, who have not. This finding raises a fundamental challenge to the traditional notion of accidental mutation. Here we address this finding with the replacement hypothesis, according to which pre-existing genetic interactions can lead directly and mechanistically to mutations that simplify and replace them. Thus, a gradual evolutionary process under selection can hone in on interactions of importance for the currently evolving adaptations, from which large-effect mutations follow that are relevant to these adaptations. We exemplify this hypothesis using multiple types of mutation, including gene fusion mutations, gene duplication mutations, A>G mutations in RNA-edited sites and transcription-associated mutations, and place it in the broader context of a system-level view of mutation origination called Interaction-based Evolution. Potential consequences include that similarity of mutation pressures may contribute to parallel evolution in genetically related species, that the evolution of genome organization may be driven by mutational mechanisms, that transposable element movements may also be explained by replacement, and that long-term directional mutational responses to specific environmental pressures are possible. Such responses need to be further tested by future studies in natural and artificial settings.

Solidification cracking is a major obstacle when joining dissimilar alloys using additive manufacturing. In this work, location-specific solidification cracking susceptibility has been investigated using an integrated computational materials engineering (ICME) approach for a graded alloy formed by mixing P91 steel and Inconel 740H superalloy. An alloy derived from a mixture of 26 wt.% P91 steel and 74 wt.% Inconel 740H, with high configurational and total entropy, was fabricated using wire-arc additive manufacturing. Microstructure characterization revealed intergranular solidification cracks, which increased in length along with the build height. With inputs from experiments, such as secondary dendrite arm spacing, the DICTRA (diffusion-controlled transformations) module within the Thermo-Calc software was used to model location-specific solidification cracking susceptibility. The top region, with the highest cooling rate, has the highest solidification cracking susceptibility and is in good agreement with the experimentally observed crack length. From Scheil simulations, it was deduced that pronounced segregation of Nb and Cu within the cracks increased the solidification range by suppressing the solidus temperature. The overall solidification cracking susceptibility and freezing range was highest for the 26 wt.% P91 alloy amongst the mixed compositions between P91 steel and 740H superalloy, proving that solidification characteristics play a major role in alloy design for additive manufacturing.

This study is a synthesis of 159 articles that were selected for their relevance to comprehend key aspects of the Massive Open Online Courses (MOOCs) phenomenon, from a discourse analysis perspective. Since 2011, MOOCs are expanding worldwide so that the number of subscribers outpointed 101 million at the end of 2018. This paper explores the question whether the MOOCs are the embodiment of the global one-world classroom or whether, instead, they represent a low-cost alternative tailored to a segment that doesn´t have enough time or resources to attend a brick-and-mortar college. In addition, the review tackles the link between motivation and low completion rates. Finally, we discuss the need to devise better methods to assess the pedagogical value of MOOCs.

Efficient implementation of clean energy technologies, including pioneering solutions like mobile solar PV systems mounted on trailers (MSPT), is pivotal for addressing energy challenges, especially in regions with constrained power grid access. This endeavour is vital for meeting escalating elec-tricity demands and aligning with the UN Sustainable Development Goal (SDG) aimed at ensuring dependable and sustainable energy provision in developing countries. This paper investigates the aerodynamic behaviour of a designed MSPT using numerical and experimental approaches. Spe-cifically, the study focuses on the effects of wind velocity and tilt angels on the drag and lift forces, as well as drag and lift coefficients on the panel used in the MSPT system. Additionally, the overall wind force acting on the entire MSPT (including 9 large solar PV panels) was examined, considering the combined effects of wind flow and the system's geometry. The simulations were conducted using ANSYS-Fluent software and experimental testing was performed utilizing scaled-down models to validate the accuracy of the simulation. The insights and the knowledge from this study can be utilized to optimize the design, installation, and operation of such systems, ultimately enhancing their performance, reliability, and paving ways for further improvements in mobile solar PV technology.

One of the most significant developments in the sports world over the last two decades has been the use of mathematical methods in conjunction with the massive amounts of data now available to analyze performances, identify trends and patterns, and forecast results. Football analytics has advanced significantly in recent years and continues to evolve as it becomes a more recognized and integral part of the game. Football analytics is also used to forecast game outcomes, allowing bettors to make educated guesses. This article describes mathematical concepts related to football analytics that enable a better betting strategies. We explain how the pitch is partitioned into different zones and we define possession sequences. Furthermore, we explain what an expected goals model is and which expected goals model we use in this research. Furthermore, we define two general characteristics of a player evaluation method, each corresponding to one of the equations of the Dawson model. Based on these characteristics, we describe the developments of several general approaches for evaluating players in the context of the Dawson model.

Proposed as a response to the increasing global need for environmental protection, a green port balances economic vibrancy and environmental protection. However, because exhaust emissions (e.g., CO2 or sulfide) are difficult to monitor in and around ports, data on such emissions are often incomplete, which hinders research on this topic. To remedy this problem, this study aimed to formulate a method for collecting CO2 emissions data at their source; this method was applied to collect real-world operating data from a large container-handling company in Taiwan. Specifically, to account for undesirable outputs, we formulated a method that combines (1) data envelopment analysis based on a modified slack-based measure and (2) a multichoice goal programming approach. We found that rubber-tired gantry cranes are the greenest and should be used. Our findings aid port managers in selecting port equipment that best balances between environmental protection and profitability.

The paper proposes TOPSIS method for solving multi-objective multi-level programming problem (MO-MLPP) with fuzzy parameters via fuzzy goal programming (FGP). At first, - cut method is used to transform the fuzzily described MO-MLPP into deterministic MO-MLPP. Then, for specific , we construct the membership functions of distance functions from positive ideal solution (PIS) and negative ideal solution (NIS) of all level decision makers (DMs). Thereafter, FGP based multi-objective decision model is established for each level DM for obtaining individual optimal solution. A possible relaxation on decisions for all DMs is taken into account for satisfactory solution. Subsequently, two FGP models are developed and compromise optimal solutions are found by minimizing the sum of negative deviational variables. To recognize the better compromise optimal solution, the concept of distance functions is utilized. Finally, a novel algorithm for MO-MLPP involving fuzzy parameters is provided and an illustrative example is solved to verify the proposed procedure.

This research aims to explore factors that influence sustainable music education from a psychological perspective, and innovatively constructs a combination of qualitative and quantitative approaches. For first time, combines stochastic nonlinear system of control theory and identifies relevant factors affecting sustainable music learning by establishing a data system for questionnaire answering and a quantitative model for actual academic performance. Existing research mainly looks at several factors that affect fragmented music education from perspective of teachers' teaching rules, emphasizing phased teaching state and learning goals of teachers as main body, thus ignoring sustainable music education and students, who are a large group of music learning objects. The research fills gap in this type of research object, focusing on sustainable music education from an emotional perspective and students who occupy a dominant position in music learning, so as to more accurately explore impact of their emotional influencing factors on sustainable music learning. The most prominent innovation of this study lies in construction of stochastic nonlinear system for psychological influencing factors of sustainable student music learning and a quantitative model for actual learning effect. Through analysis of nonlinear system, weight values of several negative emotions on sustainable music learning are obtained.

Repetitive transcranial magnetic stimulation (rTMS) with intensive occupational therapy improves upper limb motor paralysis and activities of daily living after stroke; however, amount of improvement according to paralysis severity remains unverified. Target activities for daily living using patients’ upper limb functions can be established by predicting the amount of change after treatment for each severity level of upper limb motor paralysis and further aid practice planning. This study estimated post-treatment score changes for each severity level of motor paralysis (no, poor, limited, notable, and full) stratified according to Action Research Arm Test (ARAT) scores before combined rTMS and intensive occupational therapy. Severity of motor paralysis was the fixed factor for analysis of covariance, delta (post-pre) of the scores was the dependent variable. Ordinal logistic regression analysis was used to compare changes in ARAT subscores in patients, divided according to paralysis severity before treatment. A multicenter retrospective cohort dataset analyzed 907 patients with stroke hemiplegia. Largest treatment-related changes in scores were observed in the Limited recovery group for upper limb motor paralysis and Full recovery group for quality-of-life activities using paralyzed upper limb. These results will help predict treatment effects and determine exercises and goal movements for occupational therapy after rTMS.

Using the PLCC advantages generates revenue and lowers costs more than might be anticipated. It ensures better decisions by using a more perfect and practical assessment of revenues and costs. Although the supplier selection (SC) product life cycle cost (SCPLCC) is an important consideration among corporations, SCPLCC problem has become associated with deciding how one supplier should be selected from possible alternatives. In this study, we applied two types of goal programming, multiobjective linear programming and revised multichoice goal programming to develop a PLCC-based concept to solve the SCPLCC problem and construct a decision-making tool for application to a case of supply chain management in a Taiwanese light-emitting diode company in the high-tech industry. Our study main contribution Company managers can easily use the two approaches of the SCPLCC model with different parameters to solve SCPLCC model problems. Finally, we comparing five models found RMCGP with weighted linear goal programming had an adequate effect for application to the PLCC concept for high-technology company; this cloud make company decision–makers focus on low PLCC and select better supplier.

Oxidoreductase (OXR) enzymes are in high demand for biocatalytic applications in food industry and cosmetics: glucose oxidase (GOx), cellobiose dehydrogenase (CBDH), bioremediation: horseradish peroxidase (HRP), laccase (LAC), and medicine for biosensors and miniature biofuel cells (GOx, CBDH, LAC, HRP). They can be used in a soluble form and/or within the yeast cell walls expressed as chimeras on the surface of yeast cells (YSD), such as P. pastoris and S. cerevisiae. However, most of the current studies suffer from either low yield for soluble enzyme expression or low enzyme activity when expressed as chimeric proteins using YSD. This is always the case in studies dealing with heterologous expression of oxidoreductase enzymes, since there is requirement not only for multiple OXR genes integrations into the yeast genome (super transformations), and codon optimization, but also very careful design of fermentation media composition, and fermentation conditions during expression due to need for adding transition metals (copper, iron), and metabolic precursors of FAD and heme. Therefore, scientists are still trying to find optimal formula using above mentioned approaches, and most recently also using protein engineering and directed evolution for additional increase in the yield of recombinant enzyme production. In this review article we will cover all the current state of the art technologies and most recent advances in the field that yielded high expression level for some of these enzymes in specially designed expression/fermentation systems. We will also tackle and discuss new possibilities for further increase in fermentation yield by the cutting-edge technologies such are directed evolution, protein and strain engineering, high-throughput screening methods based on in vitro compartmentalization, flow cytometry and microfluidics.

Infection with Zika virus (ZIKV), a member of the Flavivirus genus of the Flaviviridae family, typically results in mild self-limited illness, but severe neurological disease occurs in a limited subset of patients. In contrast, serious outcomes commonly occur in pregnancy that affect the developing fetus, including microcephaly and other major birth defects. The genetic similarity of ZIKV to other widespread flaviviruses, such as dengue virus (DENV), presents a challenge to the development of specific ZIKV diagnostic assays. Nonstructural protein 1 (NS1) is established for use in immunodiagnostic assays for flaviviruses. To address the cross-reactivity of ZIKV NS1 with proteins from other flaviviruses we used site-directed mutagenesis to modified putative epitopes. Goat polyclonal antibodies to variant ZIKV NS1 were affinity-purified to remove antibodies binding to the closely related NS1 protein of DENV. An antigen-capture ELISA configured with the affinity-purified polyclonal antibody showed a linear dynamic range between approximately 500 to 30 ng/mL, with a limit of detection of between 1.95 and 7.8 ng/mL. NS1 proteins from DENV, yellow fever virus, St. Louis encephalitis virus and West Nile virus showed significantly reduced reactivity in the ZIKV antigen-capture ELISA. Refinement of approaches similar to those employed here could lead to development of ZIKV-specific immunoassays suitable for use in areas where infections with related flaviviruses are common.

Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

Hybrid machine tools combining additive and subtractive processes have arisen as a solution to the increasing manufacture requirements, boosting the potentials of both technologies, while compensating and minimizing their limitations. Nevertheless, the idea of hybrid machines is relatively new and there is a notable lack of knowledge in the field. Therefore, in the present paper, an insight into the advancements of hybrid machines is given, identifying their real capabilities, together with the latest developments from an industrial context. In addition, the current situation and future perspectives of hybrid machines from the point of view of process planning, monitoring and inspection are discussed. Finally, the challenges that must be overcome and the opportunities that the hybrid machines will provide in the forthcoming years are presented.

Urban forests are critical infrastructure for mitigating environmental and social challenges cities face. Municipalities and non-governmental entities, among others, often set goals (e.g., tree planting or canopy targets) to support urban forests and their benefits. We focus on canopy goals and develop conceptual underpinnings for an analysis of where additional canopy, as one important dimension of the urban forest, can fit within the landscape, while considering factors that influence where trees can be planted and where canopy can grow – ‘practical canopy.’ We apply this in New York City (NYC) to inform the setting of a canopy goal by the NYC Urban Forest Task Force (UFTF) for the NYC Urban Forest Agenda, which may trigger a virtuous cycle that supports the urban forest there. We further develop framing for a ‘priority canopy’ analysis to understand where urban forest expansion should be prioritized given more context (e.g., environmental hazards, local preferences), which can inform how expansion of the urban forest is achieved. We estimate an opportunity for 15,899 ha of new canopy in NYC given existing opportunities and constraints (practical canopy), which, if leveraged, could result in nearly doubling the canopy as of 2017 (17,253 ha). However, like existing canopy, practical canopy is not evenly distributed, in general, or across jurisdictions and land uses. Relying solely on areas identified as practical canopy to expand the urban forest would exacerbate inequities in its distribution. We discuss how the NYC UFTF established an aspirational but achievable goal of 30% canopy cover by 2035, which was informed by this analysis and guided by priorities of equity, health, and resilience. Achievement of this goal will ultimately require a combination of protecting and stewarding the existing resource, and leveraging opportunities for tree planting. Achieving a more equitable urban forest will also require identification of priority canopy, and, in cases, creation of new opportunities for tree planting and canopy expansion. Overall, the collaborative establishment of such goals based on local context can be instrumental in creating a virtuous cycle, moving conservation actors toward exercising influence and agency within the social ecological system.

Supplier selection (SC) product life cycle cost (SCPLCC) is an important consideration among corporations, SCPLCC problem has become associated with deciding how one supplier should be selected from possible alternatives. In this study, we applied two types of goal programming, multiobjective linear programming and revised multichoice goal programming to develop a PLCC-based concept to solve the SCPLCC problem and construct a decision-making tool for application to a case of supply chain management in a Taiwanese light-emitting diode company in the high-tech industry. Our study main contribution Company managers can easily use the two approaches of the SCPLCC model with different parameters to solve SCPLCC model problems. Finally, we comparing five models found RMCGP with weighted linear goal programming had an adequate effect for application to the PLCC concept for high-technology company; this cloud makes company decision–makers focus on low PLCC and select a better supplier in sustainable supply chains goal.

The article outlines a creative approach by fusing ideas from fuzzy contractions, graph mappings, and Kannan mappings to create a brand-new notion known as "Kannan-graph-fuzzy contraction." This combination of concepts makes it possible to create a unique framework for resolving real-world issues controlled by nonlinear models. It is anticipated that using Kannan-graph-fuzzy contractions will offer a fresh approach to discussing solution existence in situations where these ideas overlap. This strategy might have a significant impact on a lot of real-world applications, proving how practical multidisciplinary techniques are for tackling issues in the real world originating from technology and engineering. The article includes several illustrated examples based on computer simulations, making the results more explicit.

Alzheimer's disease is a multifactorial neurodegenerative disorder, with Acetylcholinesterase, Butyrylcholinesterase, Beta secretase, Glycogen Synthase Kinase beta and Monoamine oxidase B playing central role in it's pathogenesis. Therefore, this research aims to discover potential curative multitarget drugs derived from African natural products capable of addressing the multifactorial characteristics of the disease. In silico approaches were used to filter a 880 african natural compounds library based on selected pharmacokinetic properties. Molecular docking against the five aforementioned proteins, followed by Molecular Mechanics with Generalised Born and Surface Area Solvation scoring for the top compounds were used to assess binding. Density Functional Theory studies were used to assess electronic transitions. Pharmacokinetic filters resulted in 200 compounds, of which only five were selected after molecular docking. Density Functional Theory and Molecular Mechanics with Generalised Born and Surface Area Solvation scoring resulted in 3 potential multitarget compounds. Compound 157 (ZINC000095485950) showed triple-target inhibitory activity against Butyrylcholinesterase, Glycogen Synthase Kinase beta and Beta-secretase, while compounds 159 (ZINC000095485952) and 696 (ZINC000039144622) showed dual-target inhibitory activity against Butyrylcholinesterase and Glycogen Synthase Kinase beta. Molecular dynamics simulation and further experimental assessments are suggested.

Laser Powder Directed Energy Deposition (LP-DED) is an Additive Manufacturing process in which a laser beam is used to generate a melt pool onto a substrate. The additional material, in form of powder material, is fed into the generated melt pool and a raised track is obtained. The LP-DED process is very powerful for different applications such as the repair operations and the production of functionally graded material, however the application is still limited and one of the main reasons is related to the lack of knowledge in the physics of the process mechanisms. The process is influenced by a huge number of parameters and three main mechanisms can be identi-fied. These mechanisms are the powder flow, the generation of the molten pool and the solidifica-tion process and for each of these mechanisms the process parameters have a different relevance. In this paper, a review of the main mechanisms and the relationship between the process parame-ters and the outcome of each step of the process is presented.

Supplier selection (SC) continues to be a crucial component in manufacturing procurement. Using the PLCC advantages generates revenue and lowers costs more than might be anticipated. Supplier selection (SC) product life cycle cost (SCPLCC) is an important consideration among corporations, SCPLCC problem has become associated with deciding how one supplier should be selected from possible alternatives. Past literature on this topic is limited. We try to close this gap in knowledge. In this study, we attempt to apply two types of goal programming, multiobjective linear programming and revised multichoice goal programming to develop a PLCC-based concept to solve the SCPLCC problem and construct a decision-making tool for application to a case of supply chain management in a Taiwanese light-emitting diode company in the high-tech industry. Our study main contribution Company managers can easily use the two approaches of the SCPLCC model with different parameters to solve SCPLCC model problems. Finally, we are comparing five models found RMCGP with weighted linear goal programming had an adequate effect for application to the PLCC concept for high-technology Company; this cloud makes company decision–makers focus on low PLCC and select a better supplier in sustainable supply chains development.

Abstract: Background and objectives: Symptomatic walled-off pancreatic necrosis is a serious local complication of acute necrotising pancreatitis. The endoscopic step-up approach is the standard treatment for symptomatic walled-off pancreatic necrosis; however, adjunctive radiologic percu-taneous drainage for this condition is controversial. This study compared the clinical and radio-logic resolution of walled-off pancreatic necrosis achieved with the endoscopic step-up approach with or without radiology-guided percutaneous drainage. Material and Methods: This retrospective, single-center cohort study enrolled patients with symp-tomatic walled-off pancreatic necrosis who underwent endoscopic transmural drainage (ETD) followed by directed endoscopic necrosectomy (DEN) with or without radiology-guided drainage. A total of 34 patients (endoscopic approach, n=22; combined modality approach, n=12) underwent the endoscopic step-up approach (ETD followed by DEN). Baseline characteristics, clinical success, and resolution of necrosis were compared between groups. Results: All patients achieved symptom resolution from walled-off pancreatic necrosis. The mean patient age was 58.4 years, and 21 (61.8%) were men. After treatment with the endoscopic approach and combined modality approach, clinical success was achieved in 90.9% of patients within 11.5 days, and 66.7% of patients within 16.5 days, respectively. Both the total hospital stay (55 days vs 71 days; p=0.071) and time to complete radiologic resolution were shorter (93 days vs 124 days; p=0.23) in the endoscopic approach group. Conclusion: The endoscopic step-up approach resulted in the clinical resolution of symptomatic walled-off pancreatic necrosis comparable to that of the combined modality drainage. However, the endoscopic approach alone allows higher clinical success, early clinical and radiologic resolution, and a shorter hospital stay.

In recent years, semantic communication has received significant attention from both academia and industry, driven by the growing demands for ultra-low latency and high-throughput capabilities in emerging intelligent services. Nonetheless, a comprehensive and effective theoretical framework for semantic communication has yet to be established. In particular, finding the fundamental limits of semantic communication, exploring the capabilities of semantic-aware networks, or utilizing theoretical guidance for deep learning in semantic communication are very important yet still unresolved issues. In general, the mathematical theory of semantic communication and the mathematical representation of semantics are referred to as semantic information theory. In this paper, we introduce the pertinent advancements in semantic information theory. Grounded in the foundational work of Claude Shannon, we present the latest developments in semantic entropy, semantic rate-distortion, and semantic channel capacity. Additionally, we analyze some open problems in semantic information measurement and semantic coding, providing a theoretical basis for the design of a semantic communication system. Furthermore, we carefully review several mathematical theories and tools and evaluate their applicability in the context of semantic communication. Finally, we shed light on the challenges encountered in both semantic communication and semantic information theory.

Despite the publication in 2009 of a paper on ‘terms and definitions of immune thrombocytopenia’, (ITP) some unresolved issues remain and are reflected by the disagreement in the treatment suggested for primary ITP in adults. Considering that these disagreements could be ascribed to non-shared goals, a ‘consensus’ to classify the different lines of treatment for primary ITP in adults according to their indications and goals was proposed in October 2018 to the XIX annual meeting of the Italian Gruppo di Studio delle Piastrine (GSP), a non-profit platelet study group of scientists and physicians. Having approved the project, 60 potential co-authors and experts in the world were invited to take part to a consensus through e-Delphy method and nine of the 12 who initially accepted the invitation completed the work. Agreement was reached on a classification of four lines of treatment for primary ITP in adults based on their indications and goals. The consensus obtained regarded also the criteria, ‘timing’ included, to consider practicable elective splenectomy in these patients. In our opinion, the classification of the lines of treatment for primary ITP in adults here proposed could facilitate the realization of better shared evidence-based guidelines for the treatment of the disease.

Within the oligometastatic state, oligo-recurrent lymph node disease in prostate cancer represents an interesting clinical entity characterized by a relatively indolent biology that makes it unique: it can be treated radically, and its treatment is usually associated with a long period of control and excellent survival. Additionally it is an emergent situation that we are facing more frequently, mainly due to: a) the incorporation into clinical practice of the PSMA PET that provides strikingly increase superior images in comparison to conventional imaging, with higher sensitivity and specificity; b) the higher detection rates of bone and node disease with extremely low levels of PSA; and c) the availability of high-precision technology in radiotherapy treatments with the incorporation of stereotaxic body radiotherapy (SBRT) or stereotaxic ablative radiotherapy (SABR) technology that allows the safe administration of high doses of radiation in a very limited number of fractions with low toxicity and excellent tolerance. This approach of new image-guided patient management is compelling for doctors and patients since it can potentially contribute to improve the clinical outcome. In this work we discuss the available evidence, areas of debate, and potential future directions concerning the utilization of new imaging guided SBRT for the treatment of nodal recurrence in prostate cancer.

The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we performed docking calculations and high-throughput electrophysiology experiments. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the “mouth” of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.

Biological technologies are fundamentally unlike any other because biology evolves. Bioengineering therefore requires novel design methodologies with evolution at their core. Knowledge about evolution is currently applied to the design of biosystems ad hoc. Unless we have a unified engineering theory of evolution, we will neither be able to meet evolution’s potential as a design tool, nor understand or limit its unintended consequences on our designs. Our concept of the evotype offers a conceptual framework for engineering the evolutionary potential of biosystems. We show how a biosystem’s evolutionary properties might be rationally designed by engineering aspects of genetic variation, designed function, and natural selection. This idea could apply to all biosystems – from individual proteins to communities of whole-cells or even entire ecosystems – whether the goal is to direct evolution in the design process, or to limit its impacts during application. These principles could even be used beyond the realm of bioengineering to design entirely synthetic evolving auto-adaptive technologies.

In line with Pomeau’s conjecture about the relevance of directed percolation (DP) to turbulence onset/decay in wall-bounded flows, we propose a minimal stochastic model dedicated to the interpretation of the spatially intermittent regimes observed in channel flow before its return to laminar flow. Numerical simulations show that a regime with bands obliquely drifting in two stream-wise symmetrical directions bifurcates into an asymmetrical regime, before ultimately decaying to laminar flow. The model is expressed in terms of a probabilistic cellular automaton evolving von Neumann neighbourhoods with probabilities educed from a close examination of simulation results. It implements band propagation and the two main local processes: longitudinal splitting involving bands with the same orientation, and transversal splitting giving birth to a daughter band with orientation opposite to that of its mother. The ultimate decay stage observed to display one-dimensional DP properties in a two-dimensional geometry is interpreted as resulting from the irrelevance of lateral spreading in the single-orientation regime. The model also reproduces the bifurcation restoring the symmetry upon variation of the probability attached to transversal splitting, which opens the way to a study of the critical properties of that bifurcation, in analogy with thermodynamic phase transitions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (M^Pro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of M^Pro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae M^Pro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of M^Pro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 M^Pro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 M^Pro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 M^Pro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.

Induction heating is a fast, reproducible, and efficient heating method used in various manufacturing processes. However, there is no established additive manufacturing (AM) process based on induction heating using wire as feedstock. This study investigates a novel approach to AM based on inductive heating, where a steel wire is melted and droplets are detached periodically using a two-winding induction coil. The process parameters and energy input into the droplets are characterized. The induction generator exhibits sluggish response to the excitation voltage, resulting in a lag in the coil current. The process is captured using a high-speed camera, revealing regular droplet formation and uniform size and shape when operated within an appropriate process window. Larger drops and increased spatter formation occur outside this window. The proposed method allows for the production of droplets with almost spherical shapes. Further analysis and characterization of droplet formation and energy input provide insights into process optimization and overall efficiency.

As distinct human societies, three unique intentional communities are investigated regarding their preferred consensus decision-making practices. It is Identified that each has adopted a different form of consensus decision-making to solve potential group-wide interpersonal conflict. The individual attributes of these three consensus decision-making practices are considered, both from the perspective of maintaining group stability and in relation to individual member's mental health. The communities are a Canadian self-directed public senior elementary and secondary school, an annual English conference for those self-identifying as on the autistic spectrum, and a self-producing Korean popular music (K-pop) group. It is found that the intentional community and participants’ mental health are sustained regarding each of the three consensus decision-making practices. Nevertheless, the resulting decisions generate various stresses within the communities, both as a whole and concerning the individual members. To retain group cohesion and maintain individual mental health, these stresses must be recognized and understood by participants. The novel finding of this research is that, dependent on the time available for decision-making, and the members’ perspective adopted, intentional communities might practice more than one form of consensus decision-making and still support both group cohesion and individual mental health, maintaining the democracy of these distinct societies.

Hemolysin II (HlyII) – one of the pathogenic factors of Bacillus cereus, a pore-forming β-barrel toxin – possesses a C-terminal extension of 94 amino acid residues, designated as the C-terminal domain of HlyII (HlyIICTD), which plays an important role in the functioning of the toxin. Our previous work described a monoclonal antibody (HlyIIC-20), capable of strain-specific inhibi-tion of hemolysis caused by HlyII, and demonstrated the dependence of the efficiency of hemol-ysis on the presence of proline at position 324 in HlyII outside the conformational antigenic de-terminant. In this work, we studied 16 mutant forms of HlyIICTD. Each of the mutations, ob-tained by multiple site-directed mutagenesis leading to the replacement of amino acid residues lying on the surface of the 3D structure of HlyIICTD, led to a decrease in the interaction of HlyIIC-20 with the mutant form of the protein. Changes in epitope structure confirm the high conformational mobility of HlyIICTD required for the functioning of HlyII. Comparison of the effect of the introduced mutations on the effectiveness of interaction between HlyIICTD and HlyIIC-20 and a control antibody recognizing a non-overlapping epitope enabled identifying the amino acid residues N339, K340 included in the conformational antigenic determinant rec-ognized by HlyIIC-20.

A variety of techniques have been utilized in metal additive manufacturing (AM) for melt pool size management, including modeling and feed-forward approaches. In a few cases, closed-loop control has been demonstrated. In this research, closed-loop melt pool size control for large-scale, laser-wire based Directed Energy Deposition is demonstrated with a novel modification: site-specific changes to the controller set-point were commanded at trigger points, the locations of which were generated by the projection of a secondary geometry onto the primary 3D-printed component geometry. The present work shows that, through this technique, it is possible to print a specific geometry that occurs beyond the actual toolpath of the print head. This is denoted as an extra-toolpath geometry and is fundamentally different from other methods of generating component features in metal AM. A proof-of-principle experiment is presented in which a complex oak leaf geometry was embossed on an otherwise ordinary double-bead wall made from Ti-6Al-4V. The process is introduced and characterized primarily from a controls perspective with reports on the performance of the control system, the melt pool size response, and the resulting geometry. The implications of this capability, which extend beyond localized control of bead geometry to the potential mitigations of defects and functional grading of component properties, are discussed.

This study explores the relationship between job satisfaction, employee loyalty and two types of flexible employment arrangements; teleworking and flexi-time. The analysis relies on data derived by the Workplace Employee Relations Survey (WERS) in 2004 and 2011. A propensity score matching and least squares regressions are applied. Furthermore, Bayesian Networks (BN) and Directed Acyclic Graphs (DAGs) are employed in order to confirm the causality between employment types explored and the outcomes of interest. Finally, an instrumental variables (IV) approach based on the BN framework is proposed and applied in this study. The results support that there is a positive causal effect from these employment arrangements on job satisfaction and employee loyalty.

The online learning necessitated by COVID-19 social distancing limitations has resulted in the utilization of hybrid online formats focused on maintaining visual contact among learners and teachers. The preferred option of video conferencing for academic meetings has become that of Zoom. The needs of one voluntary, democratic, self-reflective university research group—grounded in responses to writing prompts—differed in learning focus. Demanding a safe space to encourage and record both self-reflection and creative questioning of other participants, the private Facebook group was chosen over video conferencing to maintain the concentration on group members’ written responses rather than how they saw themselves (and thought others saw them) on screen. A narrative research model initiated in 2015, the 2020/21 interaction of the group in the year’s worth of Facebook entries, and the yearend feedback received from group participants, will be compared with previous years when the weekly group met in-person. The results in relation to COVID-19 limitations indicate that an important aspect of self-directed learning related to trust that comes from team mindfulness is lost when face-to-face interaction is eliminated regarding the democratic nature of these meetings. With online meetings the new standard, maintaining trust requires improvements to online virtual meeting spaces.

This paper draws an earlier book (with Evans and Higgins) entitled Bad Call: Technology’s Attack on Referees and Umpires and How to Fix It (hereafter Bad Call) and its various precursor papers. These show why it is that current match officiating aids are unable to provide the kind of accuracy that is often claimed for them and that sports aficianados have been led to expect from them. Accuracy is improving all the time but the notion of perfect accuracy is a myth because, for example, lines drawn on sports fields and the edges of balls are not perfectly defined. The devices meant to report the exact position of a ball – for instance ‘in’ or ‘out’ at tennis – work with the mathematically perfect world of virtual reality, not the actuality of an imperfect physical world. Even if ball-trackers could overcome the sort of inaccuracies related to fast ball speeds and slow camera frame-rates the goal of complete accuracy will always be beyond reach. Here it is suggested that the purpose of technological aids to umpires and referees be looked at in a new way that takes the viewers into account.

Labelling techniques such as electron paramagnetic resonance spectroscopy and single-molecule fluorescence resonance energy transfer, allow access to distances in the range of tens of angstroms, corresponding to the size of proteins and small to medium-sized protein complexes. Such measurements do not require long-range ordering and are therefore applicable to systems with partial disorder. Data from spin-label-based measurements can be processed into distance distributions that provide information about the extent of such disorder. Using such information in modelling presents several challenges, including a small number of restraints, the influence of the label itself on the measured distance and distribution width, and balancing the fitting quality of the long-range restraints with the fitting quality of other restraint subsets. Starting with general considerations about integrative and hybrid structural modelling, this review provides an overview of recent approaches to these problems and identifies where further progress is needed.