Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies

Diversity of teachers’ conceptions related to environment and human rights. A survey in 24 countries

The environmental, social and economical dimensions of ESD include human rights as equality of all the human beings independently to their gender, ethnic group, religion or sexual orientation. To analyse teachers’ conceptions on environment and on human rights, and to identify eventual links between them and with controlled parameters, a large survey has been done in 24 countries (8 749 teachers). The data are submitted to multivariate analyses. In the less developed countries, the teachers’ conceptions are more anthropocentric, less awareness of the problem of the limit of resources in our planet, and less reticent to use GMO (genetically modified organisms). These teachers are more believing in God, more practicing religion, more for “a strong central power”, “against the separation between science and religion”. The priority of ESD in these countries is poverty and development, while it is to avoid wasting and excessive consumption in the most developed countries. The teachers with the most anthropocentric conceptions more agree with these propositions: “It is for biological reasons that women more often than men take care of housekeeping” and “Ethnic groups are genetically different and that is why some are superior to others”, and more disagree with: “Homosexual couples should have the same rights as heterosexual couples”. These points illustrate that some socio-cultural traditions can differ from values of ESD (the universal human rights).CIEC – FCT Research Unit 317

Ultrasound-assisted extraction of natural products

Ultrasound-assisted extraction (USAE) is an interesting process to obtain high valuable compounds and could contribute to the increase in the value of some food by-products when used as sources of natural compounds. The main benefits will be a more effective extraction, thus saving energy, and also the use of moderate temperatures, which is beneficial for heat-sensitive compounds. For a successful application of the USAE, it is necessary to consider the influence of several process variables, the main ones being the applied ultrasonic power, the frequency, the extraction temperature, the reactor characteristics, and the solvent-sample interaction. The highest extraction rate is usually achieved in the first few minutes, which is the most profitable period. To optimize the process, rate equations and unambiguous process characterization are needed, aspects that have often been lacking. © 2011 Springer Science+Business Media, LLC.The authors thank the Generalitat Valenciana for their financial support in project PROMETEO/2010/062 and the Caja de Ahorros del Mediterraneo for M.D. Esclapez's pre-doctoral grant.Esclapez Vicente, MD.; García Pérez, JV.; Mulet Pons, A.; Cárcel Carrión, JA.; Esclapez, MD. (2011). Ultrasound-assisted extraction of natural products. Food Engineering Reviews. 3(2):108-120. https://doi.org/10.1007/s12393-011-9036-6S10812032Abad Romero B, Bou-Maroun E, Reparet JM, Blanquet J, Cayot N (2010) Impact of lipid extraction on the dearomatisation of an Eisenia foetida protein powder. Food Chem 119:459–466Adewuyi YG (2001) Sonochemistry: environmental science and engineering applications. Ind Eng Chem Res 40:4681–4715Atchley AA, Crum LA (1988) Acoustic cavitation and bubble dynamics. In: Suslick KS (ed) Ultrasound, its chemical, physical, and biological effects. VHS Publishers, Weinheim, pp 1–64Arnold G, Leiteritz L, Zahn S, Rohm H (2009) Ultrasonic cutting of cheese: composition affects cutting work reduction and energy demand. Int Dairy J 19:314–320Barbero GF, Liazid A, Palma M, Barroso CG (2008) Ultrasound-assisted extraction of capsaicinoids from peppers. Talanta 75:1332–1337Benedito J, Carcel JA, Sanjuan N, Mulet A (2000) Use of ultrasound to assess Cheddar cheese characteristics. Ultrasonics 38:727–730Benedito J, Carcel JA, Rossello C, Mulet A (2001) Composition assessment of raw meat mixtures using ultrasonics. Meat Sci 57:365–370Bhaskaracharya RK, Kentish S, Ashokkumar M (2009) Selected applications of ultrasonics in food processing. Food Eng Rev 1:31–49Boonkird S, Phisalaphong C, Phisalaphong M (2008) Ultrasound-assisted extraction of capsaicinoids from Capsicum frutescens on a lab- and pilot-plant scale. Ultrason Sonochem 15:1075–1079Cárcel JA, Benedito J, Bon J, Mulet A (2007) High intensity ultrasound effects on meat brining. Meat Sci 76:611–619Cárcel JA, Benedito J, Rosselló C, Mulet A (2007) Influence of ultrasound intensity on mass transfer in apple immersed in a sucrose solution. J Food Eng 78:472–479Cavitus (2009) Grape colour and flavour extraction (Pat. Pend.) for red must extraction http://www.cavitus.com . Crafers. Accessed 10 Jan 2011Chea Chua S, Ping Tan C, Mirhosseini H, Ming Lai O, Long K, Sham Baharin B (2009) Optimization of ultrasound extraction condition of phospholipids from palm-pressed fiber. J Food Eng 92:403–409Chena R, Menga F, Zhang S, Liu Z (2009) Effects of ultrahigh pressure extraction conditions on yields and antioxidant activity of ginsenoside from ginseng. Sep Purif Technol 66:340–346Chivate MM, Pandit AB (1995) Quantification of cavitation intensity in fluid bulk. Ultrason Sonochem 2:19–25Da Porto C, Decorti D (2009) Ultrasound-assisted extraction coupled with under vacuum distillation of flavour compounds from spearmint (carvone-rich) plants: comparison with conventional hydrodistillation. Ultrason Sonochem 16:795–799Da Porto C, Decorti D, Kikic I (2009) Flavour compounds of Lavandula angustifolia L. to use in food manufacturing: Comparison of three different extraction methods. Food Chem 112:1072–1078Domínguez H, Núñez MJ, Lema JM (1994) Enzymatic pretreatment to enhance oil extraction from fruits and oilseeds: a review. Food Chem 49:271–286Dong J, Liu Y, Liang Z, Wanga W (2010) Investigation on ultrasound-assisted extraction of salvianolic acid B from Salvia miltiorrhiza root. Ultrason Sonochem 17:61–65Entezari MH, Kruus P (1994) Effect of frequency on sonochemical reactions. I: oxidation of iodide. Ultrason Sonochem 1:75–79Esclapez MD, Sáez V, Milán-Yáñez D, Tudela I, Louisnard O, González-García J (2010) Sonoelectrochemical treatment of water polluted with trichloroacetic acid: from sonovoltammetry to pre-pilot plant scale. Ultrason Sonochem 17:1010–1020Ferraro V, Cruz IB, Ferreira R, Malcata JFX, Pintado ME, Castro PML (2010) Valorisation of natural extracts from marine source focused on marine by-products: review. Food Res Int 43:2221–2233Fischer CH, Hart EJ, Henglein AJ (1986) Hydrogen/deuterium isotope exchange in the hydrogen deuteride-water system under the influence of ultrasound. Phys Chem 90:3059–3060Garcia-Noguera J, Weller CL, Oliveira FIP, Rodrigues S, Fernandes FAN (2010) Dual-stage sugar substitution in strawberries with a Stevia-based sweetener. Innovative Food Sci Emerg Technol 11:225–230García-Pérez JV, Cárcel JA, de la Fuente-Blanco S, Riera-Franco de Sarabia E (2006) Ultrasonic drying of foodstuff in a fluidized bed: parametric study. Ultrasonics 44:539–543García-Pérez JV, García-Alvarado MA, Carcel JA, Mulet A (2010) Extraction kinetics modeling of antioxidants from grape stalk (Vitis vinifera var. Bobal): Influence of drying conditions. J Food Eng 101:49–58González-García J, Sáez V, Tudela I, Díez-Garcia MI, Esclapez MD, Louisnard O (2010) Sonochemical treatment of water polluted by chlorinated organocompounds. A review. Water 2:28–74Handa SS, Preet S, Khanuja S, Longo G, Rakesh DD (2008) Extraction Technologies for Medicinal and Aromatic Plants. United Nations Industrial Development Organization and the International Centre for Science and High Technology, TriesteHemwimol S, Pavasant P, Shotipruk A (2006) Ultrasound-assisted extraction of anthraquinones from roots of Morinda citrifolia. Ultrason Sonochem 13:543–548Hielscher (2011) Teltow http:// www.hielscher.com . Accessed 10 Jan 2011Hu Y, Wang T, Wang M, Han S, Wan P, Fan M (2008) Extraction of isoflavonoids from Pueraria by combining ultrasound with microwave vacuum. Chem Engin Process 47:2256–2261Ince NH, Tezcanli G, Belen RK, Apikyan PG (2001) Ultrasound as a catalyzer of aqueous reaction systems: the state of the art and environmental applications. Appl Catal B 29:167–176Jadhav D, Rekha BN, Gogate PR, Rathod VK (2009) Extraction of vanillin from vanilla pods: a comparison study of conventional soxhlet and ultrasound assisted extraction. J Food Eng 93:421–426Ji J-b, Lu X-h, Cai M-q, Xu C-c (2006) Improvement of leaching process of Geniposide with ultrasound. Ultrason Sonochem 13:455–462Kanthale PM, Gogate PR, Pandit AB, Wilhelm AM (2003) Mapping of an ultrasonic horn: link primary and secondary effects of ultrasound. Ultrason Sonochem 10:331–335Karki B, Lamsal BP, Jung S, van Leeuwen JH, Pometto AL III, Grewell D, Khanal SK (2010) Enhancing protein and sugar release from defatted soy flakes using ultrasound technology. J Food Eng 96:270–278Kardos N, Luche J-L (2001) Sonochemistry of carbohydrate compounds. Carbohydr Res 332:115–131Kotronarou A, Mills G, Hoffmann MR (1991) Ultrasonic Irradiation of para-Nitrophenol in Aqueous Solution. J Phys Chem 95:3630–3638Kuijpers MWA, Kemmere MF, Keurentjes JTF (2002) Calorimetric study of the energy efficiency for ultrasound-induced radical formation. Ultrasonics 40:675–678Leighton TG (2007) What is ultrasound? Prog Biophys Mol Biol 93:3–83Leonelli C, Mason TJ (2010) Microwave and ultrasonic processing: now a realistic option for industry. Chem Eng Process 49:885–900Li H, Pordesimo L, Weiss J (2004) High intensity ultrasound-assisted extraction of oil from soybeans. Food Res Int 37:731–738Liu J, Li J-W, Tang J (2010) Ultrasonically assisted extraction of total carbohydrates from Stevia rebaudiana Bertoni and identification of extracts. Food Bioprod Process 88:215–221Lianfu Z, Zelong L (2008) Optimization and comparison of ultrasound/microwave assisted extraction (UMAE) and ultrasonic assisted extraction (UAE) of lycopene from tomatoes. Ultrason Sonochem 15:731–737Liazid A, Schwarz M, Varela RM, Palma M, Guillén DA, Brigui J, Macías FA, Barroso CG (2010) Evaluation of various extraction techniques for obtaining bioactive extracts from pine seeds. Food Bioprod Process 88:247–252Londoño-Londoño J, Rodrigues de Lima V, Lara O, Gil A, Crecsynski Pasa TB, Arango GJ, Ramirez Pineda JR (2010) Clean recovery of antioxidant flavonoids from citrus peel: optimizing an aqueous ultrasound-assisted extraction method. Food Chem 119:81–87Lou Z, Wang H, Zhang M, Wang Z (2010) Improved extraction of oil from chickpea under ultrasound in a dynamic system. J Food Eng 98:13–18Louisnard O, González-García J, Tudela I, Klima J, Sáez V, Vargas-Hernández Y (2009) FEM simulation of a sono-reactor accounting for vibrations of the boundaries. Ultrason Sonochem 16:250–259Luque de Castro MD, Priego-Capote F (2007) Analytical Applications of Ultrasound, Vol. 26, Techniques and Instrumentation in Analytical Chemistry. Elsevier Science, AmsterdamMa Y, Ye X, Hao Y, Xu G, Xu G, Liu D (2008) Ultrasound-assisted extraction of hesperidin from Penggan (Citrus reticulata) peel. Ultrason Sonochem 15:227–232Ma Y, Chen J-C, Liu Dong-Hong, Ye X-Q (2009) Simultaneous extraction of phenolic compounds of citrus peel extracts: effect of ultrasound. Ultrason Sonochem 16:57–62Makino K, Mossoba MM, Riesz P (1982) Chemical effects of ultrasound on aqueous solutions. Evidence for hydroxyl and hydrogen free radicals (.cntdot. OH and. cntdot. H) by spin trapping. J Chem Soc 104:3537–3539Margulis MA, Margulis IM (2003) Calorimetric method for measurement of acoustic power absorbed in a volume of liquid. Ultrason Sonochem 10:343–345Martin CJ, Law ANR (1983) Design of thermistor probes for measurement of ultrasound intensity distributions. Ultrasonics 21:85–90Mason TJ, Lorimer JP, Bates DM, Zhao Y (1994) Dosimetry in sonochemistry: the use of aqueous terephthalate ion as a fluorescence monitor. Ultrason Sonochem 1:91–95Meinhardt (2011) Leipzig. http://www.meinhardt-ultraschall.de . Accessed 10 Jan 2011Montalbo-Lomboy M, Khanal SK, van Leeuwen JH, Raman DR, Dunn L Jr, Grewell D Jr (2010) Ultrasonic pretreatment of corn slurry for saccharification: a comparison of batch and continuous Systems. Ultrason Sonochem 17:939–946Mulet A, Cárcel JA, Sanjuán N, Bon J (2003) New food drying technologies. Use of ultrasound. Food Sci Technol Int 9:215–221Naguleswaran S, Vasanthan T (2010) Dry milling of field pea (Pisum sativum L.) groats prior to wet fractionation influences the starch yield and purity. Food Chem 118:627–633Orozco-Solano M, Ruiz-Jiménez J, Luque de Castro MD (2010) Ultrasound-assisted extraction and derivatization of sterols and fatty alcohols from olive leaves and drupes prior to determination by gas chromatography–tandem mass spectrometry. J Chromatogr A 1217:1227–1235Patist A, Bates D (2008) Ultrasonic innovations in the food industry: from the laboratory to commercial production. Innovative Food Sci Emerg Technol 9:147–154Price GJ (1990) The use of ultrasound for the controlled degradation of polymer solutions. In: Mason TJ (ed) Advances in sonochemistry, vol 1. Jai Press, Cambridge, pp 231–287Riener J, Noci G, Cronin DA, Morgan DJ, Lyng JG (2010) A comparison of selected quality characteristics of yoghurts prepared from thermosonicated and conventionally heated milks. Food Chem 119:1108–1113Riera E, Golás Y, Blanco A, Gallego JA, Blasco M, Mulet A (2004) Mass transfer enhancement in supercritical fluids extraction by means of power ultrasound. Ultrason Sonochem 11:241–244Riera E, Blanco A, García J, Benedito J, Mulet A, Gallego-Juárez JA, Blasco M (2010) High-power ultrasonic system for the enhancement of mass transfer in supercritical CO2 extraction processes. Physics Procedia 3:141–146Roldán-Gutiérrez JM, Ruiz-Jiménez J, Luque de Castro MD (2008) Ultrasound-assisted dynamic extraction of valuable compounds from aromatic plants and flowers as compared with steam distillation and superheated liquid extraction. Talanta 75:1369–1375Romdhane M, Gourdon C (2002) Investigation in solid–liquid extraction: influence of ultrasound. Chem Eng J 87:11–19Rong L, Kojima Y, Koda S, Nomura H (2008) Simple quantification of ultrasonic intensity using aqueous solution of phenolphthalein. Ultrason Sonochem 8:11–15Sáez V, Frias-Ferrer A, Iniesta J, Gonzalez-Garcıa J, Aldaz A, Riera E (2005) Chacterization of a 20 kHz sonoreactor. Part I: analysis of mechanical effects by classical and numerical methods. Ultrason Sonochem 12:59–65Sáez V, Frias-Ferrer A, Iniesta J, Gonzalez-Garcıa J, Aldaz A, Riera E (2005) Characterization of a 20 kHz sonoreactor. Part II: analysis of chemical effects by classical and electrochemical methods. Ultrason Sonochem 12:67–72Sahena F, Zaidul ISM, Jinap S, Karim AA, Abbas KA, Norulaini NAN, Omar AKM (2009) Application of supercritical CO2 in lipid extraction–A review. J Food Eng 95:240–253Science Direct Database (2011) www.sciencedirect.com (Data of consulting: February 2011)Soria AC, Villamiel M (2010) Effect of ultrasound on the technological properties and bioactivity of food: a review. Trends Food Sci Technol 21:323–331Starmans DAJ, Nijhuis HH (1996) Extraction of secondary metabolites from plant material: a review. Trends Food Sci Technol 7:191–197Sivakumar V, Lakshmi Anna J, Vijayeeswarri J, Swaminathan G (2009) Ultrasound assisted enhancement in natural dye extraction from beetroot for industrial applications and natural dyeing of leather. Ultrason Sonochem 16:782–789Stanisavljevic IT, Lazic ML, Veljkovic VB (2007) Ultrasonic extraction of oil from tobacco (Nicotiana tabacum L.) seeds. Ultrason Sonochem 14:646–652Sun Y, Liu D, Chen J, Ye X, Yu D (2011) Effects of different factors of ultrasound treatment on the extraction yield of the all-trans-b-carotene from citrus peels. Ultrason Sonochem 18:243–249Suslick KS (2001) Sonoluminescence and sonochemistry. In: Meyers RA (ed) Encyclopedia of physical science and technology, vol 17, 3rd edn. Academic Press, San Diego, pp 363–376Trabelsi F, Ait-Iyazidi H, Berlan J, Fabre PL, Delmas H, Wilhelm AM (1996) Electrochemical determination of the active zones in a high-frequency ultrasonic reactor. Ultrason Sonochem 3:125–130Veillet S, Tomao V, Chemat F (2010) Ultrasound assisted maceration: an original procedure for direct aromatisation of olive oil with basil. Food Chem 123:905–911Velickovic DT, Milenovic DM, Ristic MS, Veljkovic VB (2008) Ultrasonic extraction of waste solid residues from the Salvia sp. Essential oil hydrodistillation. Biochem Eng J 42:97–104Vercet A, Burgos J, Crelier S, Lopez-Buesa P (2001) Inactivation of proteases and lipases by ultrasound. Innovative Food Sci Emerg Technol 2:139–150Vilkhu K, Mawson R, Simons L, Bates D (2008) Applications and opportunities for ultrasound assisted extraction in the food industry—A review. Innovative Food Sci Emerg Technol 9:161–169Vinatoru M (2001) An overview of the ultrasonically assisted extraction of bioactive principles from herbs. Ultrason Sonochem 8:303–313Virot M, Tomao V, Le Bourvellec C, Renard CMCG, Chemat F (2010) Towards the industrial production of antioxidants from food processing by-products with ultrasound-assisted extraction. Ultrason Sonochem 17:1066–1074Wang J, Sun B, Cao Y, Tian Y, Li X (2008) Optimisation of ultrasound-assisted extraction of phenolic compounds from wheat bran. Food Chem 106:804–810Wang L, Weller CL (2006) Recent advances in extraction of nutraceuticals from plants. Trends Food Sci Technol 17:300–312Wei X, Chen M, Xiao Ja, Liu Y, Yu L, Zhang H, Wang Y (2010) Composition and bioactivity of tea flower polysaccharides obtained by different methods. Carbohydr Polym 79:418–422Weissler A, Cooper HW, Snyder S (1950) Chemical effects of ultrasonic waves: oxidation of potassium iodide solution by carbon tetrachloride. J Am Chem Soc 72:1769–1775Wulff-Pérez M, Torcello-Gómez A, Gálvez-Ruíz MJ, Martín-Rodríguez A (2009) Stability of emulsions for parenteral feeding: preparation and characterization of o/w nanoemulsions with natural oils and Pluronic f68 as surfactant. Food Hydrocolloids 23:1096–1102Yang B, Yang H, Li J, Li Z, Jiang Y (2011) Amino acid composition, molecular weight distribution and antioxidant activity of protein hydrolysates of soy sauce lees. Food Chem 124:551–555Yang Y, Zhang F (2008) Ultrasound-assisted extraction of rutin and quercetin from Euonymus alatus (Thunb.) Sieb. Ultrason Sonochem 15:308–313Zhang Z-S, Wang L-J, Li D, Jiao S-S, Chena XD, Maoa Z-H (2008) Ultrasound-assisted extraction of oil from flaxseed. Sep Purif Technol 62:192–198Zhang H-F, Yang X-H, Zhao L-D, Wang Y (2009) Ultrasonic-assisted extraction of epimedin C from fresh leaves of Epimedium and extraction mechanism. Innovative Food Sci Emerg Technol 10:54–60Zhang Q-A, Zhang Z-Q, Yue X-F, Fan X-H, Li T, Chen S-F (2009) Response surface optimization of ultrasound-assisted oil extraction from autoclaved almond powder. Food Chem 116:513–518Zhao S, Kwok K-C, Liang H (2007) Investigation on ultrasound assisted extraction of saikosaponins from Radix Bupleuri. Sep Purif Technol 55:307–312Zhu KX, Sun X-H, Zhou H-M (2009) Optimization of ultrasound-assisted extraction of defatted wheat germ proteins by reverse micelles. J Cereal Sci 50:266–271Zheng L, Sun D-W (2006) Innovative applications of power ultrasound during food freezing processes—a review. Trends Food Sci Technol 17:16–23Zou Y, Xie C, Fan G, Gu Z, Han Y (2010) Optimization of ultrasound-assisted extraction of melanin from Auricularia auricula fruit bodies. Innovative Food Sci Emerg Technol 11:611–61

HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS

Metrics for optimising the multi-dimensional value of resources recovered from waste in a circular economy: A critical review

© 2017 The Authors - Established assessment methods focusing on resource recovery from waste within a circular economy context consider few or even a single domain/s of value, i.e. environmental, economic, social and technical domains. This partial approach often delivers misleading messages for policy- and decision-makers. It fails to accurately represent systems complexity, and obscures impacts, trade-offs and problem shifting that resource recovery processes or systems intended to promote circular economy may cause. Here, we challenge such partial approaches by critically reviewing the existing suite of environmental, economic, social and technical metrics that have been regularly observed and used in waste management and resource recovery systems' assessment studies, upstream and downstream of the point where waste is generated. We assess the potential of those metrics to evaluate ‘complex value’ of materials, components and products, i.e., the holistic sum of their environmental, economic, social and technical benefits and impacts across the system. Findings suggest that the way resource recovery systems are assessed and evaluated require simplicity, yet must retain a suitable minimum level of detail across all domains of value, which is pivotal for enabling sound decision-making processes. Criteria for defining a suitable set of metrics for assessing resource recovery from waste require them to be simple, transparent and easy to measure, and be both system- and stakeholder-specific. Future developments must focus on providing a framework for the selection of metrics that accurately describe (or at least reliably proxy for) benefits and impacts across all domains of value, enabling effective and transparent analysis of resource recovery form waste in circular economy systems.We gratefully acknowledge support of the UK Natural Environ-ment Research Council (NERC) and the UK Economic and SocialResearch Council (ESRC) who funded this work in the context of‘Complex Value Optimisation for Resource Recovery’(CVORR)project (Grant No. NE/L014149/1)

Optimization of Nanoelectronic Systems Reliability under Massive Defect Density Using Distributed R-Fold Modular Redundancy

The theoretical analysis of R-fold modular redundancy with distributed voters - distributed R-fold modular redundancy in terms of reliability is presented for the first time to the best of author's knowledge. This technique is compared in terms of resistance to massive levels of defect density expected in future nano-devices to R-fold modular redundancy with a single voter, cascaded R-fold modular redundancy and NAND multiplexing. Optimal partition size analysis and redundancy optimization of distributed R-fold modular redundancy technique has been performed for the first time in the context of a large-scale system. The optimal window of application of different fault-tolerant techniques with respect to defect density, is presented as a way to find the optimum design trade-off between the reliability and power/area