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Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. Methods: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. Results: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (−) negative lungs (COVID-19−), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. Conclusions: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence. [ABSTRACT FROM AUTHOR]

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. Methods: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. Results: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (−) negative lungs (COVID-19−), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. Conclusions: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

New technologies are gaining ground in various disciplines, and road safety is not an exception. The objective of this paper is twofold: (1) to review the state-of-the-art technologies implemented in bicycles to improve cyclists' safety, and (2) to propose a classification for the levels of smartness of emerging "smart bikes". This paper defines six levels of smartness for bicycles based on their functionality and evaluates the Technology Readiness Levels of bicycle technologies. Furthermore, areas for future research were identified and discussed. To achieve these, we conducted a literature review which employed two academic databases –Scopus and Web of Science– and the Google Scholar search engine, following the framework of the systematic literature review methodology for the search and selection process. A total of 36 studies that met the inclusion criteria were investigated. The majority of these studies focus on warning systems aiming to forestall an imminent collision, mostly by using accelerometers/gyroscopes, LIDAR, sensors and networking communication. These systems, despite their preliminary state, demonstrate a positive effect on cyclists' safety. The review concludes that there is a need for further deployment and testing of such systems with field trials to gain concrete evidence regarding their impact on cyclists' safety. It also highlights that advanced technologies are scarcely implemented in bicycles and that most smart bicycle systems are based on smartphones. Thus, the question is: what lies in the future of smart bicycles from today's perspective? [ABSTRACT FROM AUTHOR]

In an innovative system, it is essential to keep under control the crucial development phases, which should consider several aspects involving, for instance, the modeling or the assessment of suitable analytical representations. Aiming to pursue a final demonstration to verify the actual capability of an engineering idea, however, some fundamental elements may have been partially considered. Many projects state the initial and final technology readiness level based on the famous scale introduced by the US National and Aeronautics Space Administration (NASA) many years ago and now widespread in many fields of technology innovation. Its nine-step definition provides a high-level indication of the maturity of the observed innovative system. Trivially, the resolution of that macroscopic meter is not made for catching advancement details, but it rather provides comprehensive information on the examined technology. It is, therefore, necessary to refer to more sophisticated analysis tools that can show a more accurate picture of the development stage and helps designers to highlight points that deserve further attention and deeper analysis. The risk is to perform a very good demonstration test that can miss generality and remain confined only to that specific experimental campaign. Moving on to these assumptions, the authors expose three realizations of theirs concerning aeronautic morphing systems, to the analysis of a well-assessed Technology Readiness Level instrument. The aim is to define the aspects to be further assessed, the aspect to be considered fully mature, and even aspects that could miss some elementary point to attain full maturation. Such studies are not so frequent in the literature, and the authors believe to give a valuable, yet preliminary, contribution to the engineering of breakthrough systems. Without losing generality, the paper refers to the 2.2 version of a tool set up by the US Air Force Research Laboratory (AFRL), and NASA, with the aim to standardize the evaluation process of the mentioned nine-step TRL. [ABSTRACT FROM AUTHOR]

In an innovative system, it is essential to keep under control the crucial development phases, which should consider several aspects involving, for instance, the modeling or the assessment of suitable analytical representations. Aiming to pursue a final demonstration to verify the actual capability of an engineering idea, however, some fundamental elements may have been partially considered. Many projects state the initial and final technology readiness level based on the famous scale introduced by the US National and Aeronautics Space Administration (NASA) many years ago and now widespread in many fields of technology innovation. Its nine-step definition provides a high-level indication of the maturity of the observed innovative system. Trivially, the resolution of that macroscopic meter is not made for catching advancement details, but it rather provides comprehensive information on the examined technology. It is, therefore, necessary to refer to more sophisticated analysis tools that can show a more accurate picture of the development stage and helps designers to highlight points that deserve further attention and deeper analysis. The risk is to perform a very good demonstration test that can miss generality and remain confined only to that specific experimental campaign. Moving on to these assumptions, the authors expose three realizations of theirs concerning aeronautic morphing systems, to the analysis of a well-assessed Technology Readiness Level instrument. The aim is to define the aspects to be further assessed, the aspect to be considered fully mature, and even aspects that could miss some elementary point to attain full maturation. Such studies are not so frequent in the literature, and the authors believe to give a valuable, yet preliminary, contribution to the engineering of breakthrough systems. Without losing generality, the paper refers to the 2.2 version of a tool set up by the US Air Force Research Laboratory (AFRL), and NASA, with the aim to standardize the evaluation process of the mentioned nine-step TRL.

Angiopoietin-like protein 3 (ANGPTL3) is a key physiological regulator of plasma lipid and lipoprotein metabolism that involves the control of enzymes, lipoprotein and endothelial lipases. Inhibition of ANGPTL3 offers a new approach for correcting the health risks of dyslipidemia, including familial hypercholesterolemia, mixed hyperlipidemia, metabolic syndrome and/or severe hypertriglyceridemia. ANGPTL3 inhibition with nucleic acid-based antisense oligonucleotide and siRNA can correct dyslipidemia chiefly by reducing production and increasing catabolism of triglyceride-rich lipoprotein and LDL particles. Early clinical trials have demonstrated that these agents can safely and effectively lower plasma triglyceride and LDL-cholesterol levels by up to 70 and 50%, respectively. However, the long-term safety and cost-effectiveness of these agents await to be confirmed in an ongoing and future clinical trials. [ABSTRACT FROM AUTHOR]

The rapid development of new infrastructure programmes requires an accelerated deployment of new materials in new environments. Materials 4.0 is crucial to achieve these goals. The application of digital to the field of materials has been at the forefront of research for many years, but there does not exist a unified means to describe a framework for this area creating pockets of development. This is confounded by the broader expectations of a digital twin (DT) as the possible answer to all these problems. The issue being that there is no accepted definition of a component DT, and what information it should contain and how it can be implemented across the product lifecycle exist. Within this position paper, a clear distinction is made between the “manufacturing DT” and the “component DT”; the former being the starting boundary conditions of the latter. In order to achieve this, we also discuss the introduction of a digital thread as a key concept in passing data through manufacturing and into service. The stages of how to define a framework around the development of DTs from a materials perspective is given, which acknowledges the difference between creating new understanding within academia and the application of this knowledge on a per-component basis in industry. A number of challenges are identified to the broad application of a component DT; all lead to uncertainty in properties and locations, resolving these requires judgments to be made in the provision of safety-dependent materials property data.

Abstract Background Lecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. However, recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size. The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size. Methods The subjects were a total of 335 patients, derived from our previous study cohort, with one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). For this study, we measured the LDL-particle size (relative LDL migration [LDL-Rm value]) by polyacrylamide gel electrophoresis in the subjects, along with the changes in the LCAT activity, at the end of a follow-up period of at least 1 year. Results The results revealed that the absolute change (Δ) in the LDL-particle size increased significantly as the quartile of Δ LCAT activity increased (p = 0.01). A multi-logistic regression adjusted-analysis revealed that Δ LCAT activity in the fourth quartile as compared to that in the first quartile was independently predictive of an increased LDL-particle size (odds ratio [95% confidence interval]: 2.03 [1.02/4.04], p = 0.04). Moreover, the ∆ LCAT activity was also positively correlated with ∆ TRL-related markers (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein B, apolipoprotein C-2, and apolipoprotein C-3). Conclusions The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in the LDL-particle size in patients at a high risk for ASCVD. To reduce the risk of ASCVD, it may be important to focus not only on the quantitative changes in the serum LDL-cholesterol levels, but also on the LCAT activity. Trial registration UMIN (https://upload.umin.ac.jp/cgi-bin/ctr/ctr_reg_list.cgi) Study ID: UMIN000033228 retrospectively registered 2 July 2018.

Enhancing the biochemical supply chain towards sustainable development requires more efforts to boost technology innovation at early design phases and avoid delays in industrial biotechnology growth. Such a transformation requires a comprehensive step-wise procedure to guide bioprocess development from laboratory protocols to commercialization. This study introduces a process design framework to guide research and development (R&D) through this journey, bearing in mind the particular challenges of bioprocess modeling. The method combines sustainability assessment and process optimization based on process efficiency indicators, technical indicators, Life Cycle Assessment (LCA), and process optimization via Water Regeneration Networks (WRN). Since many bioprocesses remain at low Technology Readiness Levels (TRLs), the process simulation module was examined in detail to account for uncertainties, providing strategies for successful guidance. The sustainability assessment was performed using the geometric mean-based sustainability footprint metric. A case study based on Chitosan production from shrimp exoskeletons was evaluated to demonstrate the method’s applicability and its advantages in product optimization. An optimized scenario was generated through a WRN to improve water management, then compared with the case study. The results confirm the existence of a possible configuration with better sustainability performance for the optimized case with a sustainability footprint of 0.33, compared with the performance of the base case (1.00).

Adrenoceptor (AR)‐linked pathways belong to the major components of the stress response system and are associated with the pathophysiology of diseases within the spectrum of metabolic syndrome. In this study, the role of adrenoceptor stimulation in serum triglyceride (TG) regulation in mice was investigated. For this purpose, α1‐ARs were activated with phenylephrine (PH) and β1/2‐ARs with isoprenaline (ISOP). Both AR agonists markedly reduced serum TG levels independently of PPARα activation. These drugs also significantly activated the hormone‐sensitive lipase in the white adipose tissue indicating increased mobilization of TGs in this tissue. In addition, PH and ISOP up‐regulated Lpl, Nr4A, Dgat1, Mttp, Aadac and Cd36 genes, critical in TG regulation, whereas the observed decrease in serum TG levels was independent of the hepatic very low‐density lipoprotein (VLDL)‐TG secretion. Interestingly, PH and ISOP also inactivated the hepatic insulin/PI3k/AKT/FoxO1 signaling pathway, holding a critical role in the regulation of genes involved in TG synthesis. Taken together, the findings of the present study indicate that stimulation of α1‐ and β1/2‐ARs markedly reduced serum TG steady‐state levels as a result of alterations in TG synthesis, uptake, transport, hydrolysis, metabolism and clearance, an effect induced by PPARα independent mechanisms. [ABSTRACT FROM AUTHOR]

Background: Lecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. However, recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size. The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size.Methods: The subjects were a total of 335 patients, derived from our previous study cohort, with one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). For this study, we measured the LDL-particle size (relative LDL migration [LDL-Rm value]) by polyacrylamide gel electrophoresis in the subjects, along with the changes in the LCAT activity, at the end of a follow-up period of at least 1 year.Results: The results revealed that the absolute change (Δ) in the LDL-particle size increased significantly as the quartile of Δ LCAT activity increased (p = 0.01). A multi-logistic regression adjusted-analysis revealed that Δ LCAT activity in the fourth quartile as compared to that in the first quartile was independently predictive of an increased LDL-particle size (odds ratio [95% confidence interval]: 2.03 [1.02/4.04], p = 0.04). Moreover, the ∆ LCAT activity was also positively correlated with ∆ TRL-related markers (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein B, apolipoprotein C-2, and apolipoprotein C-3).Conclusions: The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in the LDL-particle size in patients at a high risk for ASCVD. To reduce the risk of ASCVD, it may be important to focus not only on the quantitative changes in the serum LDL-cholesterol levels, but also on the LCAT activity.Trial Registration: UMIN ( https://upload.umin.ac.jp/cgi-bin/ctr/ctr_reg_list.cgi ) Study ID: UMIN000033228 retrospectively registered 2 July 2018. [ABSTRACT FROM AUTHOR]

Enhanced co-extraction of water in H-bonding ligands during metal ion extraction improves the stability of solvent phase. [Display omitted] • Comparison of the electronic spectra of mono and di-glycolamide extractants. • Differences in metal ion environment identified by luminescence spectroscopy. • TRLS results showing free –OH oscillators in DOHyA-Eu complexes. • Significant co-extraction of water in DOHyA during metal extraction. • The experimental results were corroborated with DFT calculations. The extraction of trivalent metal ions (Nd and Eu) in N,N,N',N'- tetraoctyldiglycolamide (TODGA) was compared with N,N -di-octyl-2-hydroxyacetamide (DOHyA), a monoglycolamide derivative of TODGA. The studies based on UV–visible spectroscopy showed the differences in Nd(III) ion complexation for the extractants in both polar and non-polar diluents. n -Dodecane modified with 5 vol% 1-octanol was employed as diluent for extraction studies with TODGA, while DOHyA was studied with no modifiers in n -Dodecane. Time resolved luminescence spectroscopy studies of the Eu(III) extracted organic phases showed strong complexation of metal ion with both the extractants. The co-extraction of water in DOHyA solvent phase during Eu(III) extraction from nitric acid medium was found to be more as compared to TODGA. The better solubilization of water in DOHyA solvent was substantiated by DFT analysis of the optimized electronic structures of Eu-DMHyA (dimethyl hydroxyacetamide) and Eu-TMDGA (tetramethyldiglycolamide) complexes. [ABSTRACT FROM AUTHOR]

The influence of hydroxybenzoic acids (HAH n ), namely p -hydroxybenzoic acid (4-hydroxybenzoic acid, HPhbH) and protocatechuic acid (3,4-dihydroxybenzoic acid, HProtoH 2 ), on the adsorption of europium(III) onto α,γ-Al 2 O 3 particles is studied as a function of acid concentration. After measuring the adsorption edge of the Eu(III)/α,γ-Al 2 O 3 binary system, and using the previously studied binary component system Eu(III)/HAH n —Moreau et al. (2015) Inorg. Chim. Acta 432 , 81—, and HAH n /α,γ-Al 2 O 3 —Moreau et al. (2013) Colloids Surf. A 435 , 97—, it is evidenced that HPhbH does not enhance Eu(III) adsorption onto α,γ-Al 2 O 3 in the Eu(III)/HPhbH/α,γ-Al 2 O 3 ternary system. Conversely, HProtoH 2 enhances Eu(III) adsorption onto α,γ-Al 2 O 3 in the Eu(III)/HProtoH 2 /α,γ-Al 2 O 3 ternary system. Adsorption of the acids are also found higher in the Eu(III)/acid/α,γ-Al 2 O 3 ternary systems as compared with the corresponding binary systems assessing synergetic effects. For high HPhbH concentrations, a ternary surface species involving ≡AlOH surface sites, Eu(III), and PhbH – is evidenced by time-resolved luminescence spectroscopy (TRLS). However, in the Eu(III)/HProtoH 2 /α,γ-Al 2 O 3 ternary system, chemical environment of Eu(III) is found to be very close to that in the Eu(III)/HProtoH 2 binary system. Ternary surface species could not be evidenced in the Eu(III)/HProtoH 2 /α,γ-Al 2 O 3 ternary system with TRLS because of the very short decay time of Eu(III) in the presence of protocatechuic acid. [ABSTRACT FROM AUTHOR]

Enhancing the biochemical supply chain towards sustainable development requires more efforts to boost technology innovation at early design phases and avoid delays in industrial biotechnology growth. Such a transformation requires a comprehensive step-wise procedure to guide bioprocess development from laboratory protocols to commercialization. This study introduces a process design framework to guide research and development (R&D) through this journey, bearing in mind the particular challenges of bioprocess modeling. The method combines sustainability assessment and process optimization based on process efficiency indicators, technical indicators, Life Cycle Assessment (LCA), and process optimization via Water Regeneration Networks (WRN). Since many bioprocesses remain at low Technology Readiness Levels (TRLs), the process simulation module was examined in detail to account for uncertainties, providing strategies for successful guidance. The sustainability assessment was performed using the geometric mean-based sustainability footprint metric. A case study based on Chitosan production from shrimp exoskeletons was evaluated to demonstrate the method's applicability and its advantages in product optimization. An optimized scenario was generated through a WRN to improve water management, then compared with the case study. The results confirm the existence of a possible configuration with better sustainability performance for the optimized case with a sustainability footprint of 0.33, compared with the performance of the base case (1.00). [ABSTRACT FROM AUTHOR]

Abstract: N,N,N′,N′-tetraoctyl diglycolamide (TODGA) has been identified as one of the promising extractants for the partitioning of minor actinides from high-level nuclear waste solutions. Solvent extraction studies have shown that stoichiometry of the extracted species of Eu3+ with TODGA depend on the nature of diluent. Time resolved luminescence spectroscopy (TRLS) has been employed to investigate the complexation of Eu3+ with TODGA under different experimental conditions. The effects of different experimental parameters such as aqueous phase acidity, nature of diluent, and TODGA concentration on the luminescence lifetime of Eu3+ ions have been investigated. The lifetime measurements of the complexed fraction of Eu3+ with TODGA suggested the absence of water molecules in the inner coordination sphere of the metal ion in different solvents. In ethanol–water (60/40%) mixture, the complexation of Eu3+ with TODGA under varying ligand-to-metal ratios suggested the formation of 1:1, 1:2, and 1:3 species, viz., Eu(TODGA)3+, Eu(TODGA)2 3+, and Eu(TODGA)3 3+, respectively. The conditional stability constants log β 1, log β 2, and log β 3 were calculated as 6.1±0.5, 10.8±0.7, and 14.3±0.6, respectively. The nature of diluent did not influence the luminescence spectra of Eu3+ in the presence of TODGA. [Copyright &y& Elsevier]

Abstract: The competition between REE, alkaline earth and d-transition metals for organic matter binding sites is still an open field of research; particularly, the mechanisms governing these phenomena need to be characterized in more detail. In this study, we examine spectroscopically the mechanisms of competitive binding of Eu(III)/Cu(II) and Eu(III)/Ca(II) pair to Gorleben humic acid (HA), as previously proposed in the framework of the NICA-Donnan model. The evolution of time-resolved laser induced luminescence spectra of humic-complexed Eu(III) showed two strikingly different environments for a comparable bound proportion for Cu(II) and Ca(II). Cu(II) seems to compete more effectively with Eu(III) inducing its release into the Donnan phase, and into the bulk solution as free Eu3+. This is evidenced both by the shapes of the spectra and by the decrease in the luminescence decay times. In contrast with that, Ca(II) induces a modification of the HA structure, which enhances the luminescence of humic-bound Eu(III), and causes a minor modification of the chemical environment of the complexed rare earth ion. [Copyright &y& Elsevier]

• Novel methodology to assess several AI technologies, by mapping them onto TRLs. • Twelve representative exemplars of AI technologies are assessed, from self-driving cars to virtual assistants. • Readiness-vs-generality charts resolve the conundrum between readiness and generality and can be used for forecasting. • Low-generality technologies achieve higher TRLs which are still inaccessible for more general capabilities. • High-layer generalities may indicate short- or mid-term massive transformative power. Artificial Intelligence (AI) offers the potential to transform our lives in radical ways. However, the main unanswered questions about this foreseen transformation are its depth , breadth and timelines. To answer them, not only do we lack the tools to determine what achievements will be attained in the near future, but we even ignore what various technologies in present-day AI are capable of. Many so-called breakthroughs in AI are associated with highly-cited research papers or good performance in some particular benchmarks. However, research breakthroughs do not directly translate into a technology that is ready to use in real-world environments. In this paper, we present a novel exemplar-based methodology to categorise and assess several AI technologies, by mapping them onto Technology Readiness Levels (TRL) (representing their depth in maturity and availability). We first interpret the nine TRLs in the context of AI, and identify several categories in AI to which they can be assigned. We then introduce a generality dimension, which represents increasing layers of breadth of the technology. These two dimensions lead to the new readiness-vs-generality charts , which show that higher TRLs are achievable for low-generality technologies, focusing on narrow or specific abilities, while high TRLs are still out of reach for more general capabilities. We include numerous examples of AI technologies in a variety of fields, and show their readiness-vs-generality charts, serving as exemplars. Finally, we show how the timelines of several AI technology exemplars at different generality layers can help forecast some short-term and mid-term trends for AI. [ABSTRACT FROM AUTHOR]