Cell Concentration Systems for Enhanced Biosensor Sensitivity

Concentration processes for analytical systems based on different types of biosensors are very important for many applications. The sample conditioning is oriented to enhance the sensitivity or directly to make the detection or analysis possible. Processes that may be used for concentration and conditioning of original samples are very diverse, depending on applications that may range from clinical diagnostics to industrial processes control, and there are different strategies to achieve the final goal

Improving the benefits of multicast prioritization algorithms

The final publication is available at Springer via http://dx.doi.org/10.1007/s11227-014-1087-zPrioritized atomic multicast consists in delivering messages in total order while ensuring that the priorities of the messages are considered; i.e., messages with higher priorities are delivered first. That service can be used in multiple applications. An example is the usage of prioritization algorithms for reducing the transaction abort rates in applications that use a replicated database system. To this end, transaction messages get priorities according to their probability of violating the existing integrity constraints. This paper evaluates how that abort reduction may be improved varying the message sending rate and the bounds set on the length of the priority reordering queue being used by those multicast algorithms.This work has been partially supported by EU FEDER and Spanish MICINN under research Grants TIN2009-14460-C03-01 and TIN2010-17193.Miedes De Elías, EP.; Muñoz Escoí, FD. (2014). Improving the benefits of multicast prioritization algorithms. Journal of Supercomputing. 68(3):1280-1301. doi:10.1007/s11227-014-1087-zS12801301683Amir Y, Danilov C, Stanton JR (2000) A low latency, loss tolerant architecture and protocol for wide area group communication. In: International Conference on Dependable Systems and Networks (DSN), IEEE-CS, Washington, DC, USA, pp 327–336Chockler G, Keidar I, Vitenberg R (2001) Group communication specifications: a comprehensive study. ACM Comput Surv 33(4):427–469CiA (2001) About CAN in Automation (CiA). http://www.can-cia.org/index.php?id=aboutciaDéfago X, Schiper A, Urbán P (2004) Total order broadcast and multicast algorithms: taxonomy and survey. ACM Comput Surv 36(4):372–421Dolev D, Dwork C, Stockmeyer L (1987) On the minimal synchronism needed for distributed consensus. J ACM 34(1):77–97International Organization for Standardization (ISO) (1993) Road vehicles—interchange of digital information—controller area network (CAN) for high-speed communication. Revised by ISO 11898-1:2003JBoss (2011) The Netty project 3.2 user guide. http://docs.jboss.org/netty/3.2/guide/html/Kaashoek MF, Tanenbaum AS (1996) An evaluation of the Amoeba group communication system. In: International conference on distributed computing system (ICDCS), IEEE-CS, Washington, DC, USA, pp 436–448Miedes E, Muñoz-Escoí FD (2008) Managing priorities in atomic multicast protocols. In: International conference on availability, reliability and security (ARES), Barcelona, Spain, pp 514–519Miedes E, Muñoz-Escoí FD (2010) Dynamic switching of total-order broadcast protocols. In: International conference on parallel and distributed processing techniques and applications (PDPTA), CSREA Press, Las Vegas, Nevada, USA, pp 457–463Miedes E, Muñoz-Escoí FD, Decker H (2008) Reducing transaction abort rates with prioritized atomic multicast protocols. In: International European conference on parallel and distributed computing (Euro-Par), Springer, Las Palmas de Gran Canaria, Spain, Lecture notes in computer science, vol 5168, pp 394–403Mocito J, Rodrigues L (2006) Run-time switching between total order algorithms. In: International European conference on parallel and distributed computing (Euro-Par), Springer, Dresden, Germany, Lecture Notes in Computer Science, vol 4128, pp 582–591Moser LE, Melliar-Smith PM, Agarwal DA, Budhia R, Lingley-Papadopoulos C (1996) Totem: a fault-tolerant multicast group communication system. Commun ACM 39(4):54–63Nakamura A, Takizawa M (1992) Priority-based total and semi-total ordering broadcast protocols. In: International conference on distributed computing systems (ICDCS), Yokohama, Japan, pp 178–185Nakamura A, Takizawa M (1993) Starvation-prevented priority based total ordering broadcast protocol on high-speed single channel network. In: 2nd International symposium on high performance distributed computing (HPDC), pp 281–288Rodrigues L, Veríssimo P, Casimiro A (1995) Priority-based totally ordered multicast. In: Workshop on algorithms and architectures for real-time control (AARTC), Ostend, BelgiumRütti O, Wojciechowski P, Schiper A (2006) Structural and algorithmic issues of dynamic protocol update. In: 20th International parallel and distributed processing symposium (IPDPS), IEEE-CS Press, Rhodes Island, GreeceTindell K, Clark J (1994) Holistic schedulability analysis for distributed hard real-time systems. Microprocess Microprogr 40(2–3):117–134Tully A, Shrivastava SK (1990) Preventing state divergence in replicated distributed programs. In: International symposium on reliable distributed systems (SRDS), Huntsville, Alabama, USA, pp 104–113Wiesmann M, Schiper A (2005) Comparison of database replication techniques based on total order broadcast. IEEE Trans Knowl Data Eng 17(4):551–56

Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death

Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented but the mechanism underlying this process is poorly understood. Here we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons, and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke

Mfn2 downregulation in excitotoxicity causes mitochondrial dysfunction and delayed neuronal death.

Mitochondrial fusion and fission is a dynamic process critical for the maintenance of mitochondrial function and cell viability. During excitotoxicity neuronal mitochondria are fragmented, but the mechanism underlying this process is poorly understood. Here, we show that Mfn2 is the only member of the mitochondrial fusion/fission machinery whose expression is reduced in in vitro and in vivo models of excitotoxicity. Whereas in cortical primary cultures, Drp1 recruitment to mitochondria plays a primordial role in mitochondrial fragmentation in an early phase that can be reversed once the insult has ceased, Mfn2 downregulation intervenes in a delayed mitochondrial fragmentation phase that progresses even when the insult has ceased. Downregulation of Mfn2 causes mitochondrial dysfunction, altered calcium homeostasis, and enhanced Bax translocation to mitochondria, resulting in delayed neuronal death. We found that transcription factor MEF2 regulates basal Mfn2 expression in neurons and that excitotoxicity-dependent degradation of MEF2 causes Mfn2 downregulation. Thus, Mfn2 reduction is a late event in excitotoxicity and its targeting may help to reduce excitotoxic damage and increase the currently short therapeutic window in stroke

Scalability approaches for causal multicast: a survey

The final publication is available at Springer via http://dx.doi.org/10.1007/s00607-015-0479-0Many distributed services need to be scalable: internet search, electronic commerce, e-government... In order to achieve scalability, high availability and fault tolerance, such applications rely on replicated components. Because of the dynamics of growth and volatility of customer markets, applications need to be hosted by adaptive, highly scalable systems. In particular, the scalability of the reliable multicast mechanisms used for supporting the consistency of replicas is of crucial importance. Reliable multicast might propagate updates in a pre-determined order (e.g., FIFO, total or causal). Since total order needs more communication rounds than causal order, the latter appears to be the preferable candidate for achieving multicast scalability, although the consistency guarantees based on causal order are weaker than those of total order. This paper provides a historical survey of different scalability approaches for reliable causal multicast protocols.This work was supported by European Regional Development Fund (FEDER) and Ministerio de Economia y Competitividad (MINECO) under research Grant TIN2012-37719-C03-01.Juan Marín, RD.; Decker, H.; Armendáriz Íñigo, JE.; Bernabeu Aubán, JM.; Muñoz Escoí, FD. (2016). Scalability approaches for causal multicast: a survey. Computing. 98(9):923-947. https://doi.org/10.1007/s00607-015-0479-0S923947989Adly N, Nagi M (1995) Maintaining causal order in large scale distributed systems using a logical hierarchy. In: IASTED Intnl Conf on Appl Inform, pp 214–219Aguilera MK, Chen W, Toueg S (1997) Heartbeat: a timeout-free failure detector for quiescent reliable communication. In: 11th Intnl Wshop on Distrib Alg (WDAG), Saarbrücken, pp 126–140Almeida JB, Almeida PS, Baquero C (2004) Bounded version vectors. In: 18th Intnl Conf Distrib Comput (DISC), Amsterdam, pp 102–116Almeida PS, Baquero C, Fonte V (2008) Interval tree clocks. In: 12th Intnl Conf Distrib Syst (OPODIS), Luxor, pp 259–274Almeida S, Leitão J, Rodrigues LET (2013) ChainReaction: a causal+ consistent datastore based on chain replication. In: 8th EuroSys Conf, Czech Republic, pp 85–98Álvarez A, Arévalo S, Cholvi V, Fernández A, Jiménez E (2008) On the interconnection of message passing systems. Inf Process Lett 105(6):249–254Amir Y, Stanton J (1998) The Spread wide area group communication system. Tech. rep., CDNS-98-4, The Center for Networking and Distributed Systems, The Johns Hopkins UnivAmir Y, Dolev D, Kramer S, Malki D (1992) Transis: a communication subsystem for high availability. In: 22nd Intnl Symp Fault-Tolerant Comp (FTCS), Boston, pp 76–84Anastasi G, Bartoli A, Spadoni F (2001) A reliable multicast protocol for distributed mobile systems: design and evaluation. IEEE Trans Parallel Distrib Syst 12(10):1009–1022Bailis P, Ghodsi A, Hellerstein JM, Stoica I (2013) Bolt-on causal consistency. In: Intnl Conf Mgmnt Data (SIGMOD), New York, pp 761–772Baldoni R, Raynal M, Prakash R, Singhal M (1996) Broadcast with time and causality constraints for multimedia applications. In: 22nd Intnl Euromicro Conf, Prague, pp 617–624Baldoni R, Friedman R, van Renesse R (1997) The hierarchical daisy architecture for causal delivery. In: 17th Intnl Conf Distrib Comput Syst (ICDCS), Maryland, pp 570–577Ban B (2002) JGroups—a toolkit for reliable multicast communication. http://www.jgroups.orgBaquero C, Almeida PS, Shoker A (2014) Making operation-based CRDTs operation-based. In: 14th Intnl Conf Distrib Appl Interop Syst (DAIS), Berlin, pp 126–140Benslimane A, Abouaissa A (2002) Dynamical grouping model for distributed real time causal ordering. Comput Commun 25:288–302Birman KP, Joseph TA (1987) Reliable communication in the presence of failures. ACM Trans Comput Syst 5(1):47–76Birman KP, Schiper A, Stephenson P (1991) Lightweigt causal and atomic group multicast. ACM Trans Comput Syst 9(3):272–314Cachin C, Guerraoui R, Rodrigues LET (2011) Introduction to reliable and secure distributed programming, 2nd edn. Springer, BerlinChandra P, Gambhire P, Kshemkalyani AD (2004) Performance of the optimal causal multicast algorithm: a statistical analysis. IEEE Trans Parall Distr 15(1):40–52Chandra TD, Toueg S (1996) Unreliable failure detectors for reliable distributed systems. J ACM 43(2):225–267de Juan-Marín R, Cholvi V, Jiménez E, Muñoz-Escoí FD (2009) Parallel interconnection of broadcast systems with multiple FIFO channels. In: 11th Intnl Symp on Distrib Obj, Middleware and Appl (DOA), Vilamoura, LNCS, vol 5870, pp 449–466Défago X, Schiper A, Urbán P (2004) Total order broadcast and multicast algorithms: taxonomy and survey. ACM Comput Surv 36(4):372–421Demers AJ, Greene DH, Hauser C, Irish W, Larson J, Shenker S, Sturgis HE, Swinehart DC, Terry DB (1987) Epidemic algorithms for replicated database maintenance. In: 6th ACM Symp on Princ of Distrib Comput (PODC), Canada, pp 1–12Du J, Elnikety S, Roy A, Zwaenepoel W (2013) Orbe: scalable causal consistency using dependency matrices and physical clocks. In: ACM Symp on Cloud Comput (SoCC), Santa Clara, pp 11:1–11:14Fernández A, Jiménez E, Cholvi V (2000) On the interconnection of causal memory systems. In: 19th Annual ACM Symp on Princ of Distrib Comput (PODC), Portland, pp 163–170Fidge CJ (1988) Timestamps in message-passing systems that preserve the partial ordering. In: 11th Australian Comput Conf, pp 56–66Friedman R, Vitenberg R, Chockler G (2003) On the composability of consistency conditions. Inf Process Lett 86(4):169–176Gilbert S, Lynch N (2002) Brewer’s conjecture and the feasibility of consistent, available, partition-tolerant web services. SIGACT News 33(2):51–59Gray J, Helland P, O’Neil PE, Shasha D (1996) The dangers of replication and a solution. In: SIGMOD Conf, pp 173–182Hadzilacos V, Toueg S (1993) Fault-tolerant broadcasts and related problems. In: Mullender S (ed) Distributed systems, chap 5, 2nd edn. ACM Press, pp 97–145Johnson S, Jahanian F, Shah J (1999) The inter-group router approach to scalable group composition. In: 19th Intnl Conf on Distrib Comput Syst (ICDCS), Austin, pp 4–14Kalantar MH, Birman KP (1999) Causally ordered multicast: the conservative approach. In: 19th Intnl Conf on Distrib Comput Syst (ICDCS), Austin, pp 36–44Kawanami S, Enokido T, Takizawa M (2004) A group communication protocol for scalable causal ordering. In: 18th Intnl Conf on Adv Inform Netw Appl (AINA), Fukuoka, pp 296–302Kawanami S, Nishimura T, Enokido T, Takizawa M (2005) A scalable group communication protocol with global clock. In: 19th Intnl Conf on Adv Inform Netw Appl (AINA), Taipei, pp 625–630Kshemkalyani AD, Singhal M (1998) Necessary and sufficient conditions on information for causal message ordering and their optimal implementation. Distrib Comput 11(2):91–111Kshemkalyani AD, Singhal M (2011) Distributed computing: principles, algorithms, and systems, 2nd edn. Cambridge University Press, New YorkLadin R, Liskov B, Shrira L, Ghemawat S (1992) Providing high availability using lazy replication. ACM Trans Comput Syst 10(4):360–391Lamport L (1978) Time, clocks, and the ordering of events in a distributed system. Commun ACM 21(7):558–565Laumay P, Bruneton E, de Palma N, Krakowiak S (2001) Preserving causality in a scalable message-oriented middleware. In: Intnl Conf on Distrib Syst Platf (Middleware), pp 311–328Liu N, Liu M, Cao J, Chen G, Lou W (2010) When transportation meets communication: V2P over VANETs. In: 30th Intnl Conf Distrib Comput Syst (ICDCS), GenovaLwin CH, Mohanty H, Ghosh RK (2004) Causal ordering in event notification service systems for mobile users. In: Intnl Conf Inform Tech: Coding Comput (ITCC), Las Vegas, pp 735–740Mahajan P, Alvisi L, Dahlin M (2011) Consistency, availability and covergence. Tech. rep., UTCS TR-11-22, The University of Texas at AustinMatos M, Sousa A, Pereira J, Oliveira R, Deliot E, Murray P (2009) CLON: overlay networks and gossip protocols for cloud environments. In: 11th Intnl Symp on Dist Obj, Middleware and Appl (DOA), Vilamoura, LNCS, vol 5870, pp 549–566Mattern F (1989) Virtual time and global states of distributed systems. In: Parallel and distributed algorithms, North-Holland, pp 215–226Mattern F, Fünfrocken S (1994) A non-blocking lightweight implementation of causal order message delivery. Lect Notes Comput Sci 938:197–213Meldal S, Sankar S, Vera J (1991) Exploiting locality in maintaining potential causality. In: 10th ACM Symp on Princ of Distrib Comp (PODC), Montreal, pp 231–239Meling H, Montresor A, Helvik BE, Babaoglu Ö (2008) Jgroup/ARM: a distributed object group platform with autonomous replication management. Softw Pract Exp 38(9):885–923Mosberger D (1993) Memory consistency models. Oper Syst Rev 27(1):18–26Mostéfaoui A, Raynal M (1993) Causal multicast in overlapping groups: towards a low cost approach. In: 4th Intnl Wshop on Future Trends of Distrib Comp Syst (FTDCS), Lisbon, pp 136–142Mostéfaoui A, Raynal M, Travers C, Patterson S, Agrawal D, El Abbadi A (2005) From static distributed systems to dynamic systems. In: 24th Symp on Rel Distrib Syst (SRDS), Orlando, pp 109–118Nishimura T, Hayashibara N, Takizawa M, Enokido T (2005) Causally ordered delivery with global clock in hierarchical group. In: ICPADS (2), Fukuoka, pp 560–564Parker DS Jr, Popek GJ, Rudisin G, Stoughton A, Walker BJ, Walton E, Chow JM, Edwards DA, Kiser S, Kline CS (1983) Detection of mutual inconsistency in distributed systems. IEEE Trans Softw Eng 9(3):240–247Pascual-Miret L (2014) Consistency models in modern distributed systems. An approach to eventual consistency. Master’s thesis, Depto. de Sistemas Informáticos y Computación, Univ. Politècnica de ValènciaPascual-Miret L, González de Mendívil JR, Bernabéu-Aubán JM, Muñoz-Escoí FD (2015) Widening CAP consistency. Tech. rep., IUMTI-SIDI-2015/003, Univ. Politècnica de València, ValenciaPeterson LL, Buchholz NC, Schlichting RD (1989) Preserving and using context information in interprocess communication. ACM Trans Comput Syst 7(3):217–246Pomares Hernández S, Fanchon J, Drira K, Diaz M (2001) Causal broadcast protocol for very large group communication systems. In: 5th Intnl Conf on Princ of Distrib Syst (OPODIS), Manzanillo, pp 175–188Prakash R, Baldoni R (2004) Causality and the spatial-temporal ordering in mobile systems. Mobile Netw Appl 9(5):507–516Prakash R, Raynal M, Singhal M (1997) An adaptive causal ordering algorithm suited to mobile computing environments. J Parallel Distrib Comput 41(2):190–204Raynal M, Schiper A, Toueg S (1991) The causal ordering abstraction and a simple way to implement it. Inf Process Lett 39(6):343–350Rodrigues L, Veríssimo P (1995a) Causal separators and topological timestamping: An approach to support causal multicast in large-scale systems. Tech. Rep. AR-05/95, Instituto de Engenharia de Sistemas e Computadores (INESC), LisbonRodrigues L, Veríssimo P (1995b) Causal separators for large-scale multicast communication. In: 15th Intnl Conf on Distrib Comput Syst (ICDCS), Vancouver, pp 83–91Schiper A, Eggli J, Sandoz A (1989) A new algorithm to implement causal ordering. In: 3rd Intnl Wshop on Distrib Alg (WDAG), Nice, pp 219–232Schiper N, Pedone F (2010) Fast, flexible and highly resilient genuine FIFO and causal multicast algorithms. In: 25th ACM Symp on Applied Comp (SAC), Sierre, pp 418–422Shapiro M, Preguiça NM, Baquero C, Zawirski M (2011) Convergent and commutative replicated data types. Bull EATCS 104:67–88Shen M, Kshemkalyani AD, Hsu TY (2015) Causal consistency for geo-replicated cloud storage under partial replication. In: Intnl Paral Distrib Proces Symp (IPDPS) Wshop, Hyderabad, pp 509–518Singhal M, Kshemkalyani AD (1992) An efficient implementation of vector clocks. Inf Process Lett 43(1):47–52Sotomayor B, Montero RS, Llorente IM, Foster IT (2009) Virtual infrastructure management in private and hybrid clouds. IEEE Internet Comput 13(5):14–22Stephenson P (1991) Fast ordered multicasts. PhD thesis, Dept. of Comp. Sc., Cornell Univ., IthacaStonebraker M (1986) The case for shared nothing. IEEE Database Eng Bull 9(1):4–9Vogels W (2009) Eventually consistent. Commun ACM 52(1):40–44Wischhof L, Ebner A, Rohling H (2005) Information dissemination in self-organizing intervehicle networks. IEEE Trans Intell Transp 6(1):90–101Yavatkar R (1992) MCP: a protocol for coordination and temporal synchronization in multimedia collaborative applications. In: 12th Intnl Conf on Distrib Comput Syst (ICDCS), Yokohama, pp 606–613Yen LH, Huang TL, Hwang SY (1997) A protocol for causally ordered message delivery in mobile computing systems. Mobile Netw Appl 2(4):365–372Zawirski M, Preguiça N, Duarte S, Bieniusa A, Balegas V, Shapiro M (2015) Write fast, read in the past: causal consistency for client-side applications. In: 16th Intnl Middleware Conf, VancouverZhou S, Cai W, Turner SJ, Lee BS, Wei J (2007) Critical causal order of events in distributed virtual environments. ACM Trans Mult Comp Commun Appl 3(3):1

A novel class of multitarget anti-Alzheimer benzohomoadamantane‒chlorotacrine hybrids modulating cholinesterases and glutamate NMDA receptors

The development of multitarget compounds against multifactorial diseases, such as Alzheimer's disease, is an area of very intensive research, due to the expected superior therapeutic efficacy that should arise from the simultaneous modulation of several key targets of the complex pathological network. Here we describe the synthesis and multitarget biological profiling of a new class of compounds designed by molecular hybridization of an NMDA receptor antagonist fluorobenzohomoadamantanamine with the potent acetylcholinesterase (AChE) inhibitor 6-chlorotacrine, using two different linker lengths and linkage positions, to preserve or not the memantine-like polycyclic unsubstituted primary amine. The best hybrids exhibit greater potencies than parent compounds against AChE (IC50 0.33 nM in the best case, 44-fold increased potency over 6-chlorotacrine), butyrylcholinesterase (IC50 21 nM in the best case, 24-fold increased potency over 6-chlorotacrine), and NMDA receptors (IC50 0.89 µM in the best case, 2-fold increased potency over the parent benzohomoadamantanamine and memantine), which suggests an additive effect of both pharmacophoric moieties in the interaction with the primary targets. Moreover, most of these compounds have been predicted to be brain permeable. This set of biological properties makes them promising leads for further anti-Alzheimer drug development

Activation of PKR Causes Amyloid ß-Peptide Accumulation via De-Repression of BACE1 Expression

BACE1 is a key enzyme involved in the production of amyloid ß-peptide (Aß) in Alzheimer's disease (AD) brains. Normally, its expression is constitutively inhibited due to the presence of the 5′untranslated region (5′UTR) in the BACE1 promoter. BACE1 expression is activated by phosphorylation of the eukaryotic initiation factor (eIF)2-alpha, which reverses the inhibitory effect exerted by BACE1 5′UTR. There are four kinases associated with different types of stress that could phosphorylate eIF2-alpha. Here we focus on the double-stranded (ds) RNA-activated protein kinase (PKR). PKR is activated during viral infection, including that of herpes simplex virus type 1 (HSV1), a virus suggested to be implicated in the development of AD, acting when present in brains of carriers of the type 4 allele of the apolipoprotein E gene. HSV1 is a dsDNA virus but it has genes on both strands of the genome, and from these genes complementary RNA molecules are transcribed. These could activate BACE1 expression by the PKR pathway. Here we demonstrate in HSV1-infected neuroblastoma cells, and in peripheral nervous tissue from HSV1-infected mice, that HSV1 activates PKR. Cloning BACE1 5′UTR upstream of a luciferase (luc) gene confirmed its inhibitory effect, which can be prevented by salubrinal, an inhibitor of the eIF2-alpha phosphatase PP1c. Treatment with the dsRNA analog poly (I∶C) mimicked the stimulatory effect exerted by salubrinal over BACE1 translation in the 5′UTR-luc construct and increased Aß production in HEK-APPsw cells. Summarizing, our data suggest that PKR activated in brain by HSV1 could play an important role in the development of AD

Gaia Early Data Release 3: Summary of the contents and survey properties

Context. We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2. Aims. A summary of the contents of Gaia EDR3 is presented, accompanied by a discussion on the differences with respect to Gaia DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of Gaia EDR3 results. Methods. The raw data collected with the Gaia instruments during the first 34 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to Gaia DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity. Results. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the (GBP − GRP) colour are also available. The passbands for G, GBP, and GRP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia-CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Conclusions. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30-40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G, GBP, and GRP is valid over the entire magnitude and colour range, with no systematics above the 1% leve

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio