The influence of coagulation factor XIII-A V34L mutation on clot formation and stability

Background: Coagulation factor XIII (FXIII) is a key enzyme in stabilising blood clots by cross-linking fibrin molecules together, amongst other effects on fibrinolysis and matrix protein stabilisation. The human FXIII-A V34L sequence variant leads to increased activation rates, forming clots with thinner fibrin fibres and smaller pores, and has been reported to show protective effects against thrombotic diseases like venous thromboembolism. However, the complete mechanism(s) underpinning this effect has hitherto remained elusive. Aim: To establish a murine FXIII-A L34V model and study the role of this sequence variant, as well as that of FXIII itself, in thromboembolic disease. Methods: FXIII-A Knock-Out (FXIII-/-, already available in the laboratory), FXIII-A 34Val (generated by MRC Harwell for Leeds) and FXIII-A 34Leu (common variant, wild-type) mice were compared in their growth, plasma FXIII activation rates (biotin incorporation assay), turbidity for clot structure, fibrinogen concentrations (ELISA assay) and FXIII-A antigen levels (westernblotting). Whole blood clotting and lysis was measured by rotational thromboelastometry (ROTEM). Whole blood clot contraction, erythrocyte extrusion (haemoglobin) and two-hour clot weights were quantified. For pulmonary and cerebral embolism models, FeCl3 vascular injury was performed on inferior vena cava and carotid artery, respectively. Lungs or brains were optically cleared and imaged with a light sheet microscope. Pulmonary emboli volume and count were quantified using software, while cerebral emboli were quantified manually. Results: No significant differences between 34Leu and 34Val mice growth, whole blood contraction, serum haemoglobin, clot weight, ROTEM, plasma FXIII-A and fibrinogen levels were observed. FXIII-/- mice plasma contained no FXIII-A antigen, showed negligible fibrin cross-linking activity and had similar levels of fibrinogen as FXIII sufficient mice. FXIII-/- clots were less firm, easier to lyse, slower to form, retained fewer red blood cells, were lighter and formed thicker fibres than FXIII sufficient clots. 34Leu mice plasma showed increased FXIII-A activation rates over 34Val mice plasma. Increasing FXIII activation rates (34Leu > 34Val > FXIII-/-) increased both pulmonary emboli count and volume, while the trend in cerebral embolism differences was inconclusive. Conclusion: The murine FXIII-A 34Leu variant showed increased activation rates over the 34Val variant and altered thromboembolisation, particularly in the venous circulation. Potentially, increased FXIII activation may enhance venous thromboembolism by protecting emboli against fibrinolysis during their transit to the lungs. In the high shear stress arterial environment, effects of mechanical stabilisation by FXIII may counterbalance any effects on fibrinolysis. These studies show a potentially important role for FXIIImediated clot stabilisation and protection against fibrinolysis that impact on thromboembolic diseases. Pulmonary embolism dependence on FXIII could be clinically relevant, where FXIII inhibition would act as prophylaxis for patients with a high risk of pulmonary embolism

Can Optogenetic Tools Determine the Importance of Temporal Codes to Sensory Information Processing in the Brain?

There is no doubt that optogenetic tools caused a paradigm shift in many fields of neuroscience. These tools enable rapid and reversible intervention with a specific neuronal circuit and then the impact on the remaining circuit and/or behavior can be studied. However, so far the ability of these optogenetic tools to interfere with neuronal signal transmission in the time scale of milliseconds has been used much less frequently although they may help to answer a fundamental question of neuroscience: how important temporal codes are to information processing in the brain. This perspective paper examines why optogenetic tools were used so little to perturb or imitate temporal codes. Although some technical limitations do exist, there is a clear need for a systems approach. More research about action potential pattern formation by interactions between several brain areas is necessary in order to exploit the full potential of optogenetic methods in probing temporal codes

Mass Personalization vs. Mass Customization: Finding Variance in Semantical Meaning and Practical Implementation between Sectors

During last 3 decades, Mass Personalization and Mass Customization as research domains have been advancedly overlooked and currently are overcoming theoretical boundaries. Ongoing digital transformation, rapidly increasing orientation to customer centric approach, demand-driven supply and value creation via online environment, platforms or tools undoubtedly influence content and development of these two paradigms too (Rungtusanatham and Salvador, 2008; Gandhi et al., 2013; Hu, 2013; KMPG, 2016; Tiihonen and Felfernig, 2017). On the other hand, a number of academic research as well as organization practices still show variances in the semantical meaning of those mentioned concepts, implementation logic and limited interaction with digitalization and value cocreation. Therefore, the research type of scoping review is based on literature analysis. It is followed throughout this article for a quality evaluation of a current standpoint and practical tendencies in the field of understanding Mass Personalization and Mass Customization, as well as defining possibilities in adapting approaches of value co-creation and technology-based attitude. Purpose – article aims to conceptualize an existing semantical gap between concepts of Mass Personalization and Mass Customization by analyzing recent scientific literature and trends in their practical implementation. Design / methodology / approach – in this research the author followed a mixed type of quantitative and qualitative methodologies. The first one is related to the method of scoping review, which is used to collect and categorize data of semantical meaning in Mass Personalization and Mass Customization concepts. The qualitative one follows methods of general and comparative scientific literature review and conceptualization of new insights later. Therefore, the design of research is described as a systematic literature review and information systemization. Finding – results of the present evaluation of the research subject suggest that mismatches in semantical understanding of analyzed concepts as well as their adoption are very common. In addition, it is noticed that approaches of value co-creation and technology-based attitude and their combination are evaluated separately or partly from the research subject. Research limitations / implications – the present article has limitations both in theoretical and practical fields. From the perspective of scientific research, it is noticed that in different periods, the focus has been switched exclusively on process standardization or Mass Customization, without conducting a multi-dimensional research. In addition, there are also limited research carried out in the field of finding content differences between Mass Personalization and Mass Customization concepts as well as their possible combination for different sectors, with a focus on non-manufacturing organizations, digitalization and data analytics. Practical implications – results of the research may be applied in practice in different sectors and different type of organizations: a) as a multi-dimensional framework and basis for conducting an internal evaluation of ongoing process status as well as a content of service in relation to Mass Customization or Mass personalization; b) as a theoretical background to set up a direction and content of changes to reach a more customized or personalized service and create an overall more customer-centric approach in an organization; c) as a summary of key points for a better understanding on main differences, requirements, trends of each concept and their practical adoption. Originality / Value – theoretical analysis created following holistic and multidimensional standpoints not only confirms existing differences between semantical meanings but also reveals possible areas of misunderstanding when applied in practical implementation. In parallel, at this point, a combined approach of value co-creation and technology-based attitude produces valuable insights for future research and might serve as a basis for ongoing process evaluation in practice

Review of a Process Prioritization in Mass Customization

Purpose – The present article aims to analyze the content of process prioritization methods and possibilities of its application in the context of Mass Customization. Design/methodology/approach – As the analysis is based on exploratory approach, qualitative methodology is the main tool used in the research. Moreover, author do not aim at providing conclusive answers to research questions; in opposition, generating relevant insights about a current situation is a goal. Findings – Results suggest that prioritization methods and principles are compatible, necessary and can be successfully applicable to Mass Customization at different process stages or even this concept types. In addition, this research reveals the need to have a combined and multidimensional prioritization at the beginning of Mass Customization processes. Research limitations/implications – Main research limitations can be divided into two parts. Firstly, when prioritization is taken into consideration, it is noticed that a limited scope of research focus on combined prioritization models as well as their effect on organizations results, especially in Public and Non-governmental sector. Secondly, in a case of concept of Mass Customization and its analysis, scientific discussions show extremum transitions to Big Data, Internet platform capabilities and overall customer flow management via modern economic theories in the last decades. Therefore, a lack of sufficient scientific attention to important parts of prioritization severely affect customer input, Design and Infrastructure of Mass Customization. In addition, both parts require not only proper understanding of the theoretical background but also following detail description of practical implication tools and guidelines as well as defining possible application effect. Since this article is based on the theoretical literature review, case studies and comparative analysis towards a practical implication are elaborated briefly. Practical implications – This research may serve as relevant insights into the context of the Mass Customization system and processes, where organizations constantly cope with prioritization by making a number of decisions on product selection, specifications, quantities, or pricing. From the perspective of process prioritization, the research serves as a concise review of main quantitative and qualitative methods, showing their demand of alignment and effect for Mass Customization. Originality/Value – The main value of the presented article can be described as a holistic theoretical focus on different types of prioritization methods and underlying points where it takes effect in Mass Customization concept. Moreover, the selected research object and findings are also valuable and applicable for organizations of different type, sector and working field

Energy Consumption Optimization of Powertrain of Electric Underground Load-Haul-Dump Mining Loader

The emissions of heavy-duty underground machinery endanger the health of human workers and increase the overall maintenance cost of the underground mine due to ventilation expenses. In addition, tightening emission standards for non-road vehicles are pushing towards greener solutions, hence, fully electric powertrains are becoming a viable alternative for many applications. An electric powertrain is not only local emission-free, but also provides a better controllably and a superior energy efficiency compared to the conventional diesel operated machines. The nature of such vehicles and their periodic duty cycles enable energy optimization and a prospect of an improved efficiency. The aim of the thesis was to reduce the energy consumption of an underground load-haul dump mining loader. As most of the energy is consumed by the powertrain of the vehicle, the traction motors are the focus of the optimization. An optimal speed profile was generated by means of Bellman’s dynamic programming algorithm in MATLAB environment. The simulation utilized dynamic asynchronous motor, battery and vehicle models built according to a real-size experimental prototype. The algorithm had been designed to solve discrete time problems; therefore, the model was discretized with adjustable dynamic accuracy where the intermediate points were obtained by linear interpolation. The optimal speed profile demonstrated a 9.1% decrease in energy consumption for a generic duty cycle. Additionally, the asynchronous motors were operated at a higher efficiency area generating less heat and in theory prolonging the lifetime of the powertrain components

Changing Patterns in Process Management and Improvement: Using RPA and RDA in Non- Manufacturing Organizations

Being, from the first sight, a complementary part of process management within an organization, process management automation draws a very broad and promising perspective to the whole business field since it is a step closer to the smarter and next level efficiency. Therefore, this particular theoretical scientific research elaborates the topic of the application of Robotic Process Automation (RPA) and Robotic Desktop Automation (RDA) concepts within the work activities in non-manufacturing organizations as this is a non-widely examined area and offers the whole specter of opportunities. Therefore, focuses are based on process management in organizations where client service is key activity and direction with soft systems and operations used as working tools. In addition, a comparative analysis of key similarities and differences of terms and practical application of RPA/RDA within the manufacturing and non-manufacturing sector is provided. Problematic areas, which this particular topic escalates, have a wide framework: first, it is noticed that the scientific field regarding the application of RPA and related concepts in combination with other process management methods (for example, Lean, Agile or Business Process Management (BPM)) has not been widely discussed. Second, in generally most of the past and ongoing scientific researches and practices tendencies and problems in process automation within the manufacturing sector field have been investigated. Accordingly, it is missing both quantitative and qualitative analyses of past and current situations in non-manufacturing business and public organizations. To generalize, it is agreed that process automation has made a notorious impact not only on the tendencies of process management within the business field but also on a society as a human resource. Therefore, investigation of this topic as a very relevant subject is essential since it has a direct and very strong impact on business cycles, technological evolution, and job market

Classification Of Nanopolymers

Nanopolymers with different structures, shapes, and functional forms have recently been prepared using several techniques. Nanopolymers are the most promising basic building blocks for mounting complex and simple hierarchical nanosystems. The applications of nanopolymers are extremely broad and polymer-based nanotechnologies are fast emerging. We propose a nanopolymer classification scheme based on self-assembled structures, non self-assembled structures, and on the number of dimensions in the nanometer range (nD). © 2008 IOP Publishing Ltd.1001Ikkala, O., Brinke Ten, G., (2004) Chem. Commu., p. 213

Hybrid wind power balance control strategy using thermal power, hydro power and flow batteries

The increased number of renewable power plants pose threat to power system balance. Their intermittent nature makes it very difficult to predict power output, thus either additional reserve power plants or new storage and control technologies are required. Traditional spinning reserve cannot fully compensate sudden changes in renewable energy power generation. Using new storage technologies such as flow batteries, it is feasible to balance the variations in power and voltage within very short period of time. This paper summarises the controlled use of hybrid flow battery, thermal and hydro power plant system, to support wind power plants to reach near perfect balance, i.e. make the total power output as close as possible to the predicted value. It also investigates the possibility of such technology to take part in the balance of the Lithuanian power system. A dynamic model of flow battery is demonstrated where it evaluates the main parameters such as power, energy, reaction time and efficiency. The required battery size is tested based on range of thermal and hydro power plant reaction times. This work suggests that power and energy of a reasonable size flow battery is sufficient to correct the load and wind power imbalance