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Recent paleoclimate reconstructions have suggested millennial-scale variability in the Indo-Pacific Warm Pool region coincident with events of the last deglaciation. Here, we present a new stalagmite oxygen isotope record from northern Borneo, which today is located near the center of the region's mean annual intertropical convergence zone. The record spans the full deglaciation, and reveals for the first time distinct oxygen isotope variations at this location connected with the Bølling-Allerød onset and the Younger Dryas event. The full deglaciation in the Borneo stalagmite proxy reconstruction appears remarkably similar to a 20–11 ka transient simulation of rainfall over the area produced using the isotope-enabled Community Earth System Model. In this model, periods of weakened Atlantic Ocean meridional overturning circulation are associated with an anomalous Western North Pacific anticyclone, which is produced in boreal autumn and shifts south over Borneo during boreal winter, causing dry conditions.

The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved "snowflake" yeast and the green alga $Volvox~carteri$. We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This 'entropic' cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing., Comment: 28 pages, 7 figures

Bisulfite sequencing is the "gold-standard" technique for DNA methylation analysis. By combining bisulfite sequencing with high-throughput, next-generation sequencing technology, we can document methylation from many thousands of individual reads (equivalent to alleles or "cells"), for multiple target regions and from many samples simultaneously. Here, we describe a next-generation bisulfite-sequencing assay for targeted DNA methylation analysis which offers scope for the simultaneous interrogation of multiple genomic loci across numerous samples.

Accurate prediction of vectors dispersal, as well as identification of adaptations that allow blood-feeding vectors to thrive in built environments, are a basis for effective disease control. Here we adopted a landscape genomics approach to assay gene flow, possible local adaptation, and drivers of population structure in Rhodnius ecuadoriensis, an important vector of Chagas disease. We used a reduced-representation sequencing technique (2b-RADseq) to obtain 2,552 SNP markers across 272 R. ecuadoriensis samples from 25 collection sites in southern Ecuador. Evidence of high and directional gene flow between seven wild and domestic population pairs across our study site indicates insecticide-based control will be hindered by repeated re-infestation of houses from the forest. Preliminary genome scans across multiple population pairs revealed shared outlier loci potentially consistent with local adaptation to the domestic setting, which we mapped to genes involved with embryogenesis and saliva production. Landscape genomic models showed elevation is a key barrier to R. ecuadoriensis dispersal. Together our results shed early light on the genomic adaptation in triatomine vectors and facilitate vector control by predicting that spatially-targeted, proactive interventions would be more efficacious than current, reactive approaches.

The three-dimensional structure of the genome is highly organized and is an important aspect of gene regulation. Chromatin interactions can be identified using chromosome conformation capture-based techniques, which rely on proximity ligation. Of these techniques, circular chromosome conformation capture sequencing (4C-seq) is used to identify all chromatin interactions occurring with a single chromosomal location (one versus all). Here we describe a 4C-seq protocol that has been optimized for primary adherent cells, for which the first digestion step is inefficient using standard 4C-seq protocols. It can, however, also be applied to other cell or tissue types. This protocol utilizes a standard DNA library preparation method using a commercial kit, and includes a description of the data processing steps.

Both asexual and sexual reproduction can provide important keys to the success of invasive species. A species with the potential for both strategies is lesser celandine (Ficaria verna), a European native with multiple subspecies that have been introduced in North America as ornamentals and escaped cultivation. Although the genetic and morphological diversity of celandine has been studied in Europe, few studies have examined North American populations. We aimed to document genotypic and phenotypic diversity at a regional scale. We compared sequence-related amplified polymorphism (SRAP) genotypes of 64 individuals collected from Columbus, Cleveland, and Cincinnati, OH. We phenotyped 129 individuals from across the same regions and from Louisville, KY, measuring trait values in an outdoor common garden experiment. The SRAP markers were highly polymorphic and revealed surprising genetic diversity. Genetic and trait variation was structured across regions, but we also saw high variation within regions. Cleveland populations differed the most genetically and morphologically, with notably smaller flowers. Of individuals that flowered, many produced expanded achenes, and all regions had individuals that made asexual bulbils. Trait data suggested subspecies verna or ficariiformis may be present in these regions. Their genetically admixed nature, along with achene production and a potential relationship between genetic diversity and the ability to produce achenes all support sexual reproduction. Sexual and asexual propagules may spread by different vectors, and our resistance analyses indicated water dispersal and habitat availability may contribute to genetic structure. These findings suggest celandine may have substantial potential for further spread and for evolutionary change.

An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L–H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced Dα H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 and 2019–2020 under Grant Agreement No. 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission. Peer Reviewed "Article signat per més de 50 autors/es: U. Stroth, D. Aguiam, E. Alessi, C. Angioni, N. Arden, R. Arredondo Parra, V. Artigues, O. Asunta, M. Balden, V. Bandaru, A. Banon-Navarro, K. Behler, A. Bergmann, M. Bergmann, J. Bernardo, M. Bernert, A. Biancalani, R. Bielajew, R. Bilato, G. Birkenmeier, T. Blanken, V. Bobkov, A. Bock, T. Body, T. Bolzonella, N. Bonanomi, A. Bortolon, B. Böswirth, C. Bottereau, A. Bottino, H. van den Brand, M. Brenzke, S. Brezinsek, D. Brida, F. Brochard, C. Bruhn, J. Buchanan, A. Buhler, A. Burckhart, Y. Camenen, B. Cannas, P. Cano Megias, D. Carlton, M. Carr, P. Carvalho, C. Castaldo, M. Cavedon, C. Cazzaniga, C. Challis, A. Chankin, C. Cianfarani, F. Clairet, S. Coda, R. Coelho, J.W. Coenen, L. Colas, G. Conway, S. Costea, D. Coster, T. Cote, A.J. Creely, G. Croci, D.J. Cruz Zabala, G. Cseh, A. Czarnecka, I. Cziegler, O. D'Arcangelo, A. Dal Molin, P. David, C. Day, M. de Baar, P. de Marné, R. Delogu, S. Denk, P. Denner, A. Di Siena, J.J. Dominguez Palacios Durán, D. Dunai, A. Drenik, M. Dreval, R. Drube, M. Dunne, B.P. Duval, R. Dux, T. Eich, S. Elgeti, A. Encheva, K. Engelhardt, B. Erdös, I. Erofeev, B. Esposito, E. Fable, M. Faitsch, U. Fantz, M. Farnik, H. Faugel, F. Felici, O. Ficker, S. Fietz, A. Figueredo, R. Fischer, O. Ford, L. Frassinetti, M. Fröschle, G. Fuchert, J.C. Fuchs, H. Fünfgelder, S. Futatani, K. Galazka, J. Galdon-Quiroga, D. Gallart Escolà, A. Gallo10, Y. Gao11, S. Garavaglia3, M. Garcia Muñoz16, B. Geiger21, L. Giannone1, S. Gibson32, L. Gil2, E. Giovannozzi18, S. Glöggler1, M. Gobbin8, J. Gonzalez Martin, T. Goodman, G. Gorini, T. Görler, D. Gradic, G. Granucci, A. Gräter, H. Greuner, M. Griener, M. Groth, A. Gude, L. Guimarais, S. Günter, G. Haas, A.H. Hakola, C. Ham, T. Happel, N. den Harder, G. Harrer, J. Harrison, V. Hauer, T. Hayward-Schneider, B. Heinemann, T. Hellsten, S. Henderson, P. Hennequin, A. Herrmann, E. Heyn, F. Hitzler, J. Hobirk, K. Höfler, J.H. Holm, M. Hölzl, C. Hopf, L. Horvath, T. Höschen, A. Houben, A. Hubbard, A. Huber, K. Hunger, V. Igochine, M. Iliasova, T. Ilkei, K. Insulander Björk, C. Ionita-Schrittwieser, I. Ivanova-Stanik, W. Jacob, N. Jaksic, F. Janky, A. Jansen van Vuuren, A. Jardin, F. Jaulmes, F. Jenko, T. Jensen, E. Joffrin, A. Kallenbach, S. Kálvin, M. Kantor, A. Kappatou, O. Kardaun, J. Karhunen4, C.-P. Käsemann, S. Kasilov, A. Kendl, W. Kernbichler, E. Khilkevitch, A. Kirk, S. Kjer Hansen, V. Klevarova, G. Kocsis, M. Koleva, M. Komm, M. Kong, A. Krämer-Flecken, K. Krieger, A. Krivska, O. Kudlacek, T. Kurki-Suonio, B. Kurzan, B. Labit, K. Lackner, F. Laggner, A. Lahtinen, P.T. Lang, P. Lauber, N. Leuthold, L. Li, J. Likonen, O. Linder, B. Lipschultz, Y. Liu, A. Lohs, Z. Lu, T. Luda di Cortemiglia, N.C. Luhmann, T. Lunt, A. Lyssoivan, T. Maceina, J. Madsen, A. Magnanimo, H. Maier, J. Mailloux, R. Maingi, O. Maj, E. Maljaars, P. Manas, A. Mancini, A. Manhard, P. Mantica, M. Mantsinen, P. Manz, M. Maraschek, C. Marchetto, L. Marrelli, P. Martin, A. Martitsch, F. Matos, M. Mayer, M.-L. Mayoral, D. Mazon, P.J. McCarthy, R. McDermott, R. Merkel, A. Merle, D. Meshcheriakov, H. Meyer, D. Milanesio, P. Molina Cabrera, F. Monaco, M. Muraca, F. Nabais, V. Naulin, R. Nazikian, R.D. Nem, A. Nemes-Czopf, G. Neu, R. Neu, A.H. Nielsen, S.K. Nielsen, T. Nishizawa, M. Nocente, J.-M. Noterdaeme, I. Novikau, S. Nowak, M. Oberkofler, R. Ochoukov, J. Olsen, F. Orain, F. Palermo, O. Pan, G. Papp, I. Paradela Perez, A. Pau, G. Pautasso, C. Paz-Soldan, P. Petersson, P. Piovesan, C. Piron, U. Plank, B. Plaum, B. Plöck, V. Plyusnin, G. Pokol, E. Poli, L. Porte, T. Pütterich, M. Ramisch, J. Rasmussen, G. Ratta, S. Ratynskaia, G. Raupp, D. Réfy, M. Reich1, F. Reimold, D. Reiser, M. Reisner, D. Reiter, T. Ribeiro, R. Riedl, J. Riesch, D. Rittich, J.F. Rivero Rodriguez, G. Rocchi, P. Rodriguez-Fernandez, M. Rodriguez-Ramos, V. Rohde, G. Ronchi, A. Ross, M. Rott, M. Rubel, D.A. Ryan, F. Ryter, S. Saarelma, M. Salewski, A. Salmi, O. Samoylov, L. Sanchis Sanchez, J. Santos, O. Sauter, G. Schall, K. Schlüter, K. Schmid, O. Schmitz, P.A. Schneider, R. Schrittwieser, M. Schubert, C. Schuster, T. Schwarz-Selinger, J. Schweinzer, E. Seliunin, A. Shabbir, A. Shalpegin, S. Sharapov, U. Sheikh, A. Shevelev, G. Sias, M. Siccinio, B. Sieglin, A. Sigalov, A. Silva, C. Silva, D. Silvagni, J. Simpson, S. Sipilä, E. Smigelskis, A. Snicker, E. Solano, C. Sommariva, C. Sozzi, G. Spizzo, M. Spolaore, A. Stegmeir, M. Stejner, J. Stober, E. Strumberge1, G. Suarez Lopez, H.-J. Sun, W. Suttrop, E. Sytova, T. Szepesi, B. Tál, T. Tala, G. Tardini, M. Tardocchi, D. Terranova, M. Teschke, E. Thorén, W. Tierens, D. Told, W. Treutterer, G. Trevisan, E. Trier, M. Tripský, M. Usoltceva, M. Valisa, M. Valovic, M. van Zeeland, F. Vannini, B. Vanovac, P. Varela, S. Varoutis, N. Vianello, J. Vicente, G. Verdoolaege, T. Vierle, E. Viezzer, I. Voitsekhovitch, U. von Toussaint, D. Wagner, X. Wang, M. Weiland, A.E. White, M. Willensdorfer, B. Wiringer, M. Wischmeier, R. Wolf, E. Wolfrum, Q. Yang, Q. Yu, R. Zagórski, I. Zammuto, T. Zehetbauer, W. Zhang, W. Zholobenko, M. Zilker, A. Zito, H. Zohm, S. Zoletnik and the EUROfusion MST1 Team "

Ferro-papikeite, ideally NaFe22+(Fe32+Al2)(Si5Al3)O22(OH)2, is a new mineral of the amphibole supergroup from the Filipstad Municipality, Värmland County, Central Sweden, where it occurs in a medium-grade felsic metavolcanic rock. Ferro-papikeite is pale brown with a translucent luster, has a colorless to very pale-brown streak, and shows no fluorescence under long-wave or short-wave ultraviolet light. Grains are subhedral, 0.4–3.0 mm in size, and show well-developed {210} cleavage. It has a Mohs hardness of ~6 and is brittle with a splintery fracture, has the characteristic perfect {210} cleavage of orthorhombic amphiboles, intersecting at ~56°, and the calculated density is 3.488 g/cm3. In transmitted plane-polarized light, ferro-papikeite is moderately pleochroic X = very pale brown, Y = Z = honey brown; X < Y = Z. Ferro-papikeite is biaxial (+), α = 1.674(2), β = 1.692(2), γ = 1.716(2), 2Vmeas = 86.2(9) and 2Vcalc = 88.3°, dispersion is r < v, weak. The orientation is: X || a, Y || b, Z || c. Ferro-papikeite is orthorhombic, space group Pnma, a = 18.628(4), b = 17.888(4), c = 5.3035(11) Å, V = 1767.2(6) Å3, Z = 4. The strongest ten X-ray diffraction lines in the powder pattern are [d in Å(I) (hkl)]: 8.255(100)(210), 3.223(39)(440), 3.057(68)(610), 2.824(28)(251), 2.674(41)(351), 2.572(56) (161,621), 2.549(38)(202), 2.501(50)(261,451), 2.158(25)(502), and 1.991(31)(661). Chemical analysis by electron microprobe gave SiO2 36.50, Al2O3 22.24, TiO2 0.09, FeO 31.54, MnO 0.65, MgO 5.48, CaO 0.08, Na2O 2.35, F 0.22, H2Ocalc 1.85, O=F –0.09, sum 100.91 wt%. The formula unit, calculated on the basis of 24 (O+OH+F) with (OH) = 2 apfu and Fe3+ = 0.13 apfu (determined from the distance) is A(Na0.70Ca0.01)B+C(Mg1.25Fe3.902+Mn0.082+Al1.62Fe0.132+Ti0.014+)Σ6.99T(Si5.60Al2.40)Σ8O22(OH1.89F0.11)2. The crystal structure of ferro-papikeite was refined to an R-index of 3.60% using 2335 unique observed reflections collected with MoKa X-radiation. [4]Al3+ is ordered over the four T sites as follows: T1B > T1A > T2B >> T2a, [6]Al3+ is completely ordered at M2, and Fe2+ is strongly ordered at M4. The A site is split with Na+ strongly ordered at A1. End-member ferro-papikeite is related to end-member gedrite, ☐Mg2(Mg3Al2)(Si6Al2)O22(OH)2, by the substitutions Na+ → ☐, Fe2+ → Mg, and Al3+ → Si4+. The description of ferro-papikeite as a new species further emphasizes the compositional similarities between the monoclinic calcium amphiboles and the orthorhombic magnesium-iron-manganese amphiboles.

The European Demonstration Fusion Power Reactor (EU-DEMO) has to operate in a completely tritium self-sufficient mode after initial start-up, which includes producing excess tritium to allow the start-up of other reactors. The initial start-up inventory is mainly dictated by operational inventories in the fuel cycle (FC). Advances in FC technologies and immediate recycling of a large fraction of the torus exhaust gas in the direct internal recycling loop are expected to contribute greatly to an overall low operational inventory. The remainder of the torus exhaust gas, as well as tritium from the blankets, nevertheless requires treatment in the tritium plant in order to perform the necessary purification and isotope rebalancing. Here, the employed systems still feature significant operational inventories and predominantly require steady-state operation in order to maximize their performance. In this paper the operational tritium inventories in the major FC systems are reported based on the pre-concept FC design. Additionally, major dependencies of these inventories on key design drivers of the FC are discussed. It is predicted that the EU-DEMO FC will be able to operate with an overall tritium inventory of less than 2 kg.

We present recent highlights from the most recent operation phases of Wendelstein 7-X, the most advanced stellarator in the world. Stable detachment with good particle exhaust, low impurity content, and energy confinement times exceeding 100 ms, have been maintained for tens of seconds. Pellet fueling allows for plasma phases with reduced ion-temperature-gradient turbulence, and during such phases, the overall confinement is so good (energy confinement times often exceeding 200 ms) that the attained density and temperature profiles would not have been possible in less optimized devices, since they would have had neoclassical transport losses exceeding the heating applied in W7-X. This provides proof that the reduction of neoclassical transport through magnetic field optimization is successful. W7-X plasmas generally show good impurity screening and high plasma purity, but there is evidence of longer impurity confinement times during turbulence-suppressed phases. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under Grant Agreement No. 633053. Peer Reviewed Article signat per 497 autors/es: Thomas Sunn Pedersen1,2,∗ , I. Abramovic3, P. Agostinetti4, M. Agredano Torres1, S. Äkäslompolo1, J. Alcuson Belloso1, P. Aleynikov1, K. Aleynikova1, M. Alhashimi1, A. Ali1, N. Allen5, A. Alonso6, G. Anda7, T. Andreeva1, C. Angioni8, A. Arkhipov8, A. Arnold1, W. Asad8, E. Ascasibar6, M.-H. Aumeunier9, K. Avramidis10, E. Aymerich11, S.-G. Baek3, J. Bähner1, A. Baillod12, M. Balden1, M. Balden8, J. Baldzuhn1, S. Ballinger3, M. Banduch1, S. Bannmann1, A. Banon Navarro8, A. Bañon Navarro ´ 1, T. Barbui13, C. Beidler1, C. Belafdil9, A. Bencze7, A. Benndorf1, M. Beurskens1, C. Biedermann1, O. Biletskyi14, B. Blackwell15, M. Blatzheim1, T. Bluhm1, D. Böckenhoff1, G. Bongiovi16, M. Borchardt1, D. Borodin17, J. Boscary8, H. Bosch1,18, T. Bosmann19, B. Böswirth8, L. Böttger1, A. Bottino8, S. Bozhenkov1, R. Brakel1, C. Brandt1, T. Bräuer1, H. Braune1, S. Brezinsek17, K. Brunner1, S. Buller1, R. Burhenn1, R. Bussiahn1, B. Buttenschön1, A. Buzás7, V. Bykov1, I. Calvo6, K. Camacho Mata1, I. Caminal20, B. Cannas11, A. Cappa6, A. Carls1, F. Carovani1, M. Carr21, D. Carralero6, B. Carvalho22, J. Casas20, D. Castano-Bardawil17, F. Castejon6, N. Chaudhary1, I. Chelis23, A. Chomiczewska24, J.W. Coenen13,17, M. Cole1, F. Cordella25, Y. Corre9, K. Crombe26, G. Cseh7, B. Csillag7, H. Damm1, C. Day10, M. de Baar27, E. De la Cal6, S. Degenkolbe1, A. Demby13, S. Denk3, C. Dhard1, A. Di Siena8,28, A. Dinklage12, T. Dittmar17, M. Dreval14, M. Drevlak1, P. Drewelow1, P. Drews17, D. Dunai7, E. Edlund3, F. Effenberg29, G. Ehrke1, M. Endler1, D.A. Ennis5, F.J. Escoto6, T. Estrada6, E. Fable8, N. Fahrenkamp1, A. Fanni11, J. Faustin1, J. Fellinger1, Y. Feng1, W. Figacz4, E. Flom13, O. Ford1, T. Fornal24, H. Frerichs13, S. Freundt1, G. Fuchert1, M. Fukuyama30, F. Füllenbach1, G. Gantenbein10, Y. Gao1, K. Garcia13, J.M. García Regaña6, I. García-Cortés6, J. Gaspar31, D.A. Gates29, J. Geiger1, B. Geiger13, L. Giudicotti32, A. González6, A. Goriaev26,33, D. Gradic1, M. Grahl1, J.P. Graves12, J. Green13, E. Grelier9, H. Greuner8, S. Groß1, H. Grote1, M. Groth34, M. Gruca24, O. Grulke1,35, M. Grün1, J. Guerrero Arnaiz1, S. Günter8, V. Haak1, M. Haas1, P. Hacker1, A. Hakola36, A. Hallenbert1, K. Hammond29, X. Han17,37, S.K. Hansen3, J.H. Harris38, H. Hartfuß1, D. Hartmann1, D. Hathiramani1, R. Hatzky8, J. Hawke39, S. Hegedus7, B. Hein8, B. Heinemann8, P. Helander12, S. Henneberg1, U. Hergenhahn8,40, C. Hidalgo6, F. Hindenlang8, M. Hirsch1, U. Höfel1, K.P. Hollfeld17, A. Holtz1, D. Hopf8, D. Höschen17, M. Houry9, J. Howard19, X. Huang41, M. Hubeny17, S. Hudson29, K. Ida9, Y. Igitkhanov10, V. Igochine8, S. Illy10, C. Ionita-Schrittwieser42, M. Isobe39, M. Jabłczynska ´ 24, S. Jablonski24, B. Jagielski1, M. Jakubowski1, A. Jansen van Vuuren1, J. Jelonnek10, F. Jenko8, F. Jenko8, T. Jensen35, H. Jenzsch1, P. Junghanns8, J. Kaczmarczyk24, J. Kallmeyer1, U. Kamionka1, M. Kandler8, S. Kasilov43, Y. Kazakov26, D. Kennedy1, A. Kharwandikar1, M. Khokhlov1, C. Kiefer8, C. Killer1, A. Kirschner17, R. Kleiber1, T. Klinger12, S. Klose1, J. Knauer1, A. Knieps17, F. Köchl44, G. Kocsis7, Ya.I. Kolesnichenko45, A. Könies1, R. König1, J. Kontula34, P. Kornejew1, J. Koschinsky, M.M. Kozulia14, A. Krämer-Flecken17, R. Krampitz1, M. Krause1, N. Krawczyk24, T. Kremeyer1, L. Krier10, D.M. Kriete5, M. Krychowiak1, I. Ksiazek46, M. Kubkowska24, M. Kuczynski1, G. Kühner1, A. Kumar15, T. Kurki-Suonio34, S. Kwak1, M. Landreman47, P.T. Lang8, A. Langenberg1, H.P. Laqua12, H. Laqua1, R. Laube1, S. Lazerson1, M. Lewerentz1, C. Li17, Y. Liang17, Ch. Linsmeier17, J. Lion1, A. Litnovsky17,48, S. Liu37, J. Lobsien1, J. Loizu12, J. Lore38, A. Lorenz1, U. Losada6, F. Louche26, R. Lunsford29, V. Lutsenko45, M. Machielsen12, F. Mackel8, J. Maisano-Brown3, O. Maj8, D. Makowski49, G. Manduchi50, E. Maragkoudakis6, O. Marchuk17, S. Marsen1, E. Martines4, J. Martinez-Fernandez6, M. Marushchenko1, S. Masuzaki41, D. Maurer5, M. Mayer8, K.J. McCarthy6, O. Mccormack4, P. McNeely1, H. Meister8, B. Mendelevitch8, S. Mendes1, A. Merlo1, A. Messian26, A. Mielczarek49, O. Mishchenko1, B. Missal1, R. Mitteau9, V.E. Moiseenko14, A. Mollen1, V. Moncada9, T. Mönnich1, T. Morisaki41, D. Moseev1, G. Motojima41, S. Mulas6, M. Mulsow1, M. Nagel1, D. Naujoks1, V. Naulin35, T. Neelis19, H. Neilson29, R. Neu8, O. Neubauer17, U. Neuner1, D. Nicolai17, S.K. Nielsen35, H. Niemann1, T. Nishiza1, T. Nishizawa1, T. Nishizawa8, C. Nührenberg1, R. Ochoukov8, J. Oelmann17, G. Offermanns17 K. Ogawa41, S. Okamura41, J. Ölmanns17, J. Ongena26, J. Oosterbeek1, M. Otte1, N. Pablant29, N. Panadero Alvarez6, N. Panadero Alvarez6, A. Pandey1, E. Pasch1, R. Pavlichenko14, A. Pavone1, E. Pawelec46, G. Pechstein1, G. Pelka24, V. Perseo1, B. Peterson41, D. Pilopp1, S. Pingel1, F. Pisano11, B. Plöckl8, G. Plunk1, P. Pölöskei1, B. Pompe2, A. Popov51, M. Porkolab3, J. Proll19, M.J. Pueschel19,27, M.-E. Puiatti52, A. Puig Sitjes1, F. Purps1, K. Rahbarnia1, M. Rasinski ´ 17, J. Rasmussen35, A. Reiman29, F. Reimold1, M. Reisner8, D. Reiter17, M. Richou9, R. Riedl8, J. Riemann1, K. Riße1, G. Roberg-Clark1, V. Rohde8, J. Romazanov17, D. Rondeshagen1, P. Rong1, L. Rudischhauser1, T. Rummel1, K. Rummel1, A. Runov1, N. Rust1, L. Ryc24, P. Salembier20, M. Salewski35, E. Sanchez6, S. Satake41, G. Satheeswaran17, J. Schacht1, E. Scharff1, F. Schauer8, J. Schilling1, G. Schlisio1, K. Schmid8, J. Schmitt5, O. Schmitz13, W. Schneider1, M. Schneider1, P. Schneider8, R. Schrittwieser42, T. Schröder1, M. Schröder1, R. Schroeder1, B. Schweer26, D. Schwörer1, E. Scott1, E. Scott8, B. Shanahan1, G. Sias11, P. Sichta29, M. Singer1, P. Sinha29, S. Sipliä34, C. Slaby1, M. Sleczka53, H. Smith1, J. Smoniewski54, E. Sonnendrücker8, M. Spolaore4, A. Spring1, R. Stadler8, D. Stanczak24, T. Stange1, I. Stepanov26, L. Stephey13, J. Stober8, U. Stroth8,55, E. Strumberger8, C. Suzuki41, Y. Suzuki41, J. Svensson1, T. Szabolics7, T. Szepesi7, M. Szücs7, F.L. Tabares6, N. Tamura41, A. Tancetti35, C. Tantos10, J. Terry3, H. Thienpondt6, H. Thomsen1, M. Thumm10, J.M. Travere9, P. Traverso5, J. Tretter8, E. Trier8, H. Trimino Mora1, T. Tsujimura41, Y. Turkin1, A. Tykhyi45, B. Unterberg17, P. van Eeten1, B.Ph. van Milligen6, M. van Schoor26, L. Vano1, S. Varoutis10, M. Vecsei7, L. Vela56, J.L. Velasco6, M. Vervier17, N. Vianello50, H. Viebke1, R. Vilbrandt1, G. Vogel8, N. Vogt1, C. Volkhausen1, A. von Stechow1, F. Wagner1, E. Wang17, H. Wang57, F. Warmer1, T. Wauters26, L. Wegener1, T. Wegner1, G. Weir1, U. Wenzel1, A. White3, F. Wilde1, F. Wilms1, T. Windisch1, M. Winkler1, A. Winter1, V. Winters1, R. Wolf118, A.M. Wright29, G.A. Wurden39, P. Xanthopoulos1, S. Xu17, H. Yamada58, H. Yamaguchi41, M. Yokoyama41, M. Yoshinuma41, Q. Yu8, M. Zamanov14, M. Zanini1, M. Zarnstorff29, D. Zhang1, S. Zhou17, J. Zhu1, C. Zhu29, M. Zilker8, A. Zocco1, H. Zohm8, S. Zoletnik7 and L. Zsuga7 // 1 Max Planck Institute for Plasma Physics, Garching and Greifswald, Germany: 2 University of Greifswald, Greifswald, Germany; 3 Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA 02139, United States of America; 4 Consorzio RFX, Corso Stati Uniti, 4-35127 Padova, Italy; 5 Auburn University, Auburn, AL 36849, United States of America; 6 CIEMAT, Avenida Complutense, 40, 28040 Madrid, Spain; 7 Center for Energy Research, Konkoly-Thegeut 29-33, 1121 Budapest, Hungary; 8 Max-Planck-Institute for Plasma Physics, Boltzmannstraße 2, 85748 Garching bei München, Germany; 9 CEA Cadarache, 13115 Saint-Paul-lez-Durance, France; 10 Karlsruhe Institute of Technology, Kaiserstr. 12, 76131 Karlsruhe, Germany; 11 University of Cagliari, Via Universita, 40, 09124 Cagliari, Italy; 12 École Polytechnique Fédérale de Lausanne, Swiss Plasma Center, CH-1015 Lausanne, Switzerland; 13 University of Wisconsin–Madison, Engineering Drive, Madison, WI 53706, United States of America; 14 Institute of Plasma Physics, National Science Center ‘Kharkiv Institute of Physics and Technology’, Kharkiv, Ukraine; 15 The Australian National University, Acton ACT 2601, Canberra, Australia; 16 Department of Engineering, University of Palermo, Viale delle Scienze, Edificio 6, Palermo, 90128, Italy; 17 Forschungszentrum Jülich GmbH, Institut für Energie-und Klimaforschung—Plasmaphysik, 52425 Jülich, Germany; 18 Technical University of Berlin, Strasse des 17. Juni 135, 10623 Berlin, Germany; 19 Eindhoven University of Technology, 5600 MB Eindhoven, Netherlands; 20 Universitat Politècnica de Catalunya. BarcelonaTech, C. Jordi Girona, 31, 08034 Barcelona, Spain; 21 Culham Center for Fusion Energy, Abingdon OX14 3EB, United Kingdom; 22 Instituto de Plasmas e Fusao Nuclear, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; 23 Department of Physics, National and Kapodistrian University of Athens, 15784 Athens, Greece; 24 Institute of Plasma Physics and Laser Microfusion, 23 Hery Str., 01-497 Warsaw, Poland; 25 ENEA—Centro Ricerche Frascati, Via Enrico Fermi, 45, 00044 Frascati RM, Italy; 26 Laboratory for Plasma Physics, LPP-ERM/KMS, TEC Partner, B-1000 Brussels, Belgium; 27 Dutch Institute for Fundamental Energy Research, PO Box 6336, 5600 HH Eindhoven, Netherlands; 28 University of Texas, Austin, TX, United States of America; 29 Princeton Plasma Physics Laboratory, Princeton, NJ 08543, United States of America; 30 Kyushu University, 744 Motooka Nishi-ku, Fukuoka 819-0395, Japan; 31 Aix-Marseille University, Jardin du Pharo, 58 Boulevard Charles Livon, 13007, Marseille, France; 32 Department of Physics and Astronomy, Padova University, Via Marzolo 8, 35131 Padova, Italy; 33 Department of Applied Physics, Ghent University, Sint-Pietersnieuwstraat 41 B4, 9000 Ghent, Belgium; 34 Aalto University, 02150 Espoo, Finland; 35 Department of Physics, Technical University of Denmark, Anker Engelunds Vej, 2800 Kgs Lyngby, Denmark; 36 VTT Technical Research Center of Finland Ltd., PO Box 1000, FI-02044 VTT, Finland; 37 Institute of Plasma Physics, Chinese Academy of Sciences, 230031 Hefei, Anhui, China; 38 Oak Ridge National Laboratory, 1 Bethel Valley Rd, Oak Ridge, TN 37830, United States of America; 39 Los Alamos National Laboratory, NM 87545, United States of America; 40 Fritz-Haber-Institut der Max-Planck-Gesellschaft, 14195 Berlin, Germany; 41 National Institute for Fusion Science, National Institutes of Natural Sciences, 322-6 Oroshi-cho, Toki, Gifu Prefecture 509-5292, Japan; 42 Institute for Ion Physics and Applied Physics, University of Innsbruck, Innsbruck, Austria; 43 Graz University of Technology, Rechbauerstraße 12, 8010 GRAZ, Austria; 44 Austrian Academy of Science, Doktor-Ignaz-Seipel-Platz 2, 1010 Wien, Austria; 45 Institute for Nuclear Research, prospekt Nauky 47, Kyiv 03028, Ukraine; 46 University of Opole, plac Kopernika 11a, 45-001 Opole, Poland; 47 University of Maryland, Paint Branch Drive, College Park, MA 20742, United States of America; 48 National Research Nuclear University MEPhI, 115409 Moscow, Russian Federation; 49 Department of Microelectronics and Computer Science, Lodz University of Technology, Wolczanska 221/223, 90-924 Lodz, Poland; 50 Consiglio Nazionale delle Ricerche, Piazzale Aldo Moro, 7, 00185 Roma, Italy; 51 Ioffe Physical-Technical Institute of the Russian Academy of Sciences, 26 Politekhnicheskaya, St Petersburg 194021, Russian Federation; 52 Istituto di Fisica del Plasma Piero Caldirola, Via Roberto Cozzi, 53, 20125 Milano, Italy; 53 University of Szczecin, 70-453, aleja Papieza Jana Pawła II 22A, Szczecin, Poland; 54 Lawrence University, 711 E Boldt Way, Appleton, WI 54911, United States of America; 55 Physik-Department E28, Technische Universität München, 85747 Garching, Germany; 56 Universidad Carlos III de Madrid, Av. de la Universidad, 30 Madrid, Spain; 57 Yale University, New Haven, CT 06520, United States of America; 58 University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chhiab 277-0882, Japan Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant Objectius de Desenvolupament Sostenible::7 - Energia Assequible i No Contaminant::7.a - Per a 2030, augmentar la cooperació internacional per tal de facilitar l’accés a la investigació i a les tecnolo­gies energètiques no contaminants, incloses les fonts d’energia renovables, l’eficiència energètica i les tecnologies de combustibles fòssils avançades i menys contaminants, i promoure la inversió en infraestructures energètiques i tecnologies d’energia no contaminant

Alarge superconducting machine, JT-60SA has been constructed to provide major contributions to the ITER program and DEMO design. For the success of the ITER project and fusion reactor, understanding and development of plasma controllability in ITER and DEMO relevant higher beta regimes are essential. JT-60SA has focused the program on the plasma controllability for scenario development and risk mitigation in ITER as well as on investigating DEMO relevant regimes. This paper summarizes the high research priorities and strategy for the JT-60SA project. Recent works on simulation studies to prepare the plasma physics and control experiments are presented, such as plasma breakdown and equilibrium controls, hybrid and steady-state scenario development, and risk mitigation techniques. Contributions of JT-60SA to ITER and DEMOhave been clarified through those studies. Peer Reviewed Article escrit per 127 autors/autores: M Yoshida, G Giruzzi, N Aiba, J F Artaud, J Ayllon-Guerola, L Balbinot, OBeeke, E Belonohy, P Bettini, W Bin, A Bierwage, T Bolzonella, M Bonotto, CBoulbe, J Buermans, M Chernyshova, S Coda, R Coelho, S Davis, C Day, GDeTommasi, M Dibon, A Ejiri, G Falchetto, A Fassina, B Faugeras, L Figini, M Fukumoto, S Futatani, K Galazka, J Garcia, M Garcia-Muñoz, L Garzotti, L Giacomelli, L Giudicotti, S Hall, N Hayashi, C Hoa, M Honda, K Hoshino, M Iafrati, A Iantchenko, S Ide, S Iio, R Imazawa, S Inoue, A Isayama, E Joffrin, K Kamiya, Y Ko, M Kobayashi, T Kobayashi, G Kocsis, A Kovacsik, T Kurki-Suonio, B Lacroix, P Lang, Ph Lauber, A Louzguiti, E de la Luna, G Marchiori, M Mattei, A Matsuyama, S Mazzi, A Mele, F Michel, Y Miyata, J Morales, P Moreau, A Moro, T Nakano, M Nakata, E Narita, R Neu, S Nicollet, M Nocente, S Nowak, F P Orsitto, V Ostuni, Y Ohtani, N Oyama, R Pasqualotto, B Pégourié, E Perelli, L Pigatto, C Piccinni, A Pironti, P Platania, B Ploeckl, D Ricci, P Roussel, G Rubino, R Sano, K Särkimäki, K Shinohara, S Soare, C Sozzi, S Sumida, T Suzuki, Y Suzuki, T Szabolics, T Szepesi, Y Takase, M Takech, N Tamura, K Tanaka, H Tanaka, M Tardocchi, A Terakado, H Tojo, T Tokuzawa, A Torre, N Tsujii, H Tsutsui, Y Ueda, H Urano, M Valisa, M Vallar, J Vega, F Villone, T Wakatsuki, T Wauters, M Wischmeier, S Yamoto, L Zani

Accurate assessment of chemotherapy response provides the means to terminate ineffective treatment, trial alternative drug regimens or schedules and reduce dose to minimize toxicity. Here, we have compared circulating tumor DNA (ctDNA) with carcinoembryonic antigen (CEA) for the cycle by cycle assessment of chemotherapy response in 30 patients with metastatic colorectal cancer. CtDNA (quantified using individualized digital droplet PCR (ddPCR) assays) and CEA levels were determined immediately prior to each chemotherapy cycle over time periods ranging from 42–548 days (average of 10 time points/patient). Twenty-nine/thirty (97%) patients had detectable ctDNA compared with 83% whose tumors were CEA-positive (>5 ng/ml) during the monitoring course. Over the course of treatment, 20 disease progression events were detected by computed tomography; ctDNA predicted significantly more of these events than CEA (16 (80%) versus 6 (30%), respectively; P-value = 0.004). When progression was detected by both ctDNA and CEA, the rise in ctDNA occurred significantly earlier than CEA (P-value = 0.046). Partial responses to chemotherapy were also detected more frequently by ctDNA, although this was not significant (P-value = 0.07). In addition, another 28 colorectal cancer patients who underwent potentially curative surgery and showed no evidence of residual disease were monitored with ctDNA for up to 2 years. Clinical relapse was observed in 6/28 (21%) patients. Four out of 6 of these patients showed a significant increase in ctDNA at or prior to relapse. Overall, ctDNA analyses were able to be performed in a clinically relevant timeline and were a more sensitive and responsive measure of tumor burden than CEA.

Functional landscape connectivity is vital for the conservation of wildlife species. Landscape connectivity models often overlook factors such as mortality and asymmetry in landscape resistance that can have a significant impact on functional connectivity. Individual-based models (IBMs) can be used to explore such factors through the implementation of mechanistic dispersal behavior. Furthermore, population-level patterns of animal dispersal and landscape connectivity resulting from the simulation of alternative landscapes or scenarios of animal behavior can be compared. Use an IBM to evaluate the effects of disperser mortality, asymmetrical dispersal due to landscape structure, and land-use change on the functional landscape connectivity between two populations of reintroduced American martens Martes americana. We applied a previously calibrated IBM of marten dispersal to simulate movement between two reintroduced populations in Wisconsin and Michigan, USA. We used machine learning analyses to determine how each factor affected dispersal between populations (connectivity) across five consecutive generations. Functional landscape connectivity between populations was not always correlated with more traditional dispersal metrics, such as dispersal distance. Mortality had the greatest impact on functional connectivity. Land-use change and landscape configuration affected connectivity mostly when mortality was not incorporated into simulations. These experimental factors had a stronger effect on long-distance dispersal between populations than on more local dispersal. Conservation planning for landscape connectivity may benefit from accounting for mortality risks within matrix habitat. The development of individual-based models that incorporate landscape heterogeneity and complex animal behaviors when investigating long-distance dispersal can provide unique and specific insights into both landscape connectivity and wildlife conservation.

Purpose To report the 3-month results of a randomized trial (Femtosecond Laser-Assisted Cataract Trial [FACT]) comparing femtosecond laser-assisted cataract surgery (FLACS) with standard phacoemulsification cataract surgery (PCS). Design Multicenter, randomized controlled trial funded by the UK National Institute of Health Research (HTA 13/04/46/). Participants Seven hundred eighty-five patients with age-related cataract. Methods This trial took place in 3 hospitals in the UK National Health Service (NHS). Randomization (1:1) was stratified by site, surgeon, and 1 or both eyes eligible using a secure web-based system. Postoperative assessments were masked to the allocated intervention. The primary outcome was unaided distance visual acuity (UDVA) in the study eye at 3 months. Secondary outcomes included corrected distance visual acuity, complications, and patient-reported outcomes measures. The noninferiority margin was 0.1 logarithm of the minimum angle of resolution (logMAR). ISRCTN.com registry, number ISRCTN77602616. Main Outcome Measures We enrolled 785 participants between May 2015 and September 2017 and randomly assigned 392 to FLACS and 393 to PCS. At 3 months postoperatively, mean UDVA difference between treatment arms was −0.01 logMAR (−0.05 to 0.03), and mean corrected distance visual acuity difference was −0.01 logMAR (95% confidence interval [CI], −0.05 to 0.02). Seventy-one percent of both FLACS and PCS cases were within ±0.5 diopters (D) of the refractive target, and 93% of FLACS and 92% of PCS cases were within ±1.0 D. There were 2 posterior capsule tears in the PCS arm and none in the FLACS arm. There were no significant differences between arms for any secondary outcome. Conclusions Femtosecond laser-assisted cataract surgery is not inferior to conventional PCS surgery 3 months after surgery. Both methods are as good in terms of vision, patient-reported health, and safety outcomes at 3 months. Longer-term outcomes of the clinical effectiveness and cost-effectiveness are awaited.

Background This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. Methods IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. Results Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. Conclusions In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. Trial registration NCT02164513 (GSK study number CTT116855).

Here we report electron-microprobe data and unit-cell parameters for jinshajiangite, ideally NaBaFe2+4Ti2(Si2O7)2O2(OH)2F, from a new locality: the Oktyabr'skii massif in the coastal area of the Azov Sea, Donetsk region, Ukraine. Chemical analysis by electron microprobe gave Nb2O5 1.59, ZrO2 0.61, TiO2 17.07, SiO2 27.60, Al2O3 0.08, Fe2O3 2.04, FeO 16.42, BaO 9.81, ZnO 0.76, MnO 12.97, CaO 1.82, MgO 0.07, K2O 2.05, Na2O 2.51, F 2.48, H2O 1.92, O = F –1.04, sum 98.76 wt.%; H2O was determined in accord with the required number of monovalent anions for the Ti-dominant perraultite-type minerals: OH + F = 3 pfu; the Fe3+/Fe2+ ratio was assigned in accord with Mössbauer-spectroscopy results for jinshajiangite from a different locality. The empirical formula calculated on the basis of 19 (O + F) is (Na0.71Ca0.28□0.01)Σ1(Ba0.56K0.38□0.06)Σ1(Fe2+1.99Mn1.59Fe3+0.22Zn0.08Mg0.02Al0.01□0.09)Σ4 (Ti1.86Nb0.10Zr0.04)Σ2(Si4.00O14)O2[(OH)1.86F0.14]Σ2F1.00, Z = 4. Unit-cell parameters from the single-crystal data were determined by least-squares refinement of 9807 reflections with I > 10σI and are as follows: a = 10.726(8), b = 13.834(10), c = 11.065(8) Å, α = 108.172(5), β = 99.251(7), γ = 90.00(1)°, V = 1537.5(3.4) Å3, space group C .

A structure hierarchy is developed for chain-, ribbon- and tube-silicate based on the connectedness of one-dimensional polymerisations of (TO4)n−tetrahedra, where T = Si4+plus P5+, V5+, As5+, Al3+, Fe3+, B3+, Be2+, Zn2+and Mg2+. Such polymerisations are described by ageometrical repeat unit(with ngtetrahedra) and atopological repeat unit(or graph) (with ntvertices). The connectivity of the tetrahedra (vertices) in the geometrical (topological) repeat units is denoted by the expressioncTr(cVr) wherecis the connectivity (degree) of the tetrahedron (vertex) andris the number of tetrahedra (vertices) of connectivity (degree)cin the repeat unit. ThuscTr=1Tr12Tr23Tr34Tr4(cVr=1Vr12Vr23Vr34Vr4) represents all possible connectivities (degrees) of tetrahedra (vertices) in the geometrical (topological) repeat units of such one-dimensional polymerisations. We may generate all possiblecTr(cVr) expressions for chains (graphs) with tetrahedron (vertex) connectivities (degrees)c= 1 to 4 wherer= 1 tonby sequentially increasing the values ofcandr, and by ranking them accordingly. The silicate (sensu lato) units of chain-, ribbon- and tube-silicate minerals are identified and associated with the relevantcTr(cVr) symbols. Following description and association with the relevantcTr(cVr) symbols of the silicate units in all chain-, ribbon- and tube-silicate minerals, the minerals are arranged into decreasing O:T ratio from 3.0 to 2.5, an arrangement that reflects their increasing structural connectivity. Considering only the silicate component, the compositional range of the chain-, ribbon- and tube-silicate minerals strongly overlaps that of the sheet-silicate minerals. Of the chain-, ribbon- and tube-silicates and sheet silicates with the same O:T ratio, some have the samecVrsymbols (vertex connectivities) but the tetrahedra link to each other in different ways and are topologically different. The abundance of chain-, ribbon- and tube-silicate minerals decreases as O:T decreases from 3.0 to 2.5 whereas the abundance of sheet-silicate minerals increases from O:T = 3.0 to 2.5 and decreases again to O:T = 2.0. Some of the chain-, ribbon- and tube-silicate minerals have more than one distinct silicate unit: (1) vinogradovite, revdite, lintisite (punkaruaivite) and charoite have mixed chains, ribbons and/or tubes; (2) veblenite, yuksporite, miserite and okenite have clusters or sheets in addition to chains, ribbons and tubes. It is apparent that some chain-ribbon-tube topologies are favoured over others as of the ~450 inosilicate minerals, ~375 correspond to only four topologically unique graphs, the other ~75 minerals correspond to ~46 topologically unique graphs.

Ecosystem-based management, spatial orientation, a multilevel policy framework and integration have all been identified as essential components of effective marine spatial planning (MSP). Integration has been noted by researchers and through international forums as being essential to achieve effective oceans governance. However, integrated policy approaches are the most difficult policies to design, develop and implement. They require a holistic rather than sectoral focus; horizontal and vertical jurisdictional support and coordination; and the involvement of a diverse group of stakeholders including industry, NGOs, and local communities. Integrated policies are prone to failure but if “integrative capacity” exists, integration in MSP can contribute to its success. This paper examines the role of integration within MSP and suggests a framework for determining effective integration and “integrative capacity”. It refers to different marine spatial planning examples which demonstrate that integrative capacity can contribute to the success, failure and longevity of MSP and ecosystem-based management.

We implemented multilocus selection in a spatially-explicit, individual-based framework that enables multivariate environmental gradients to drive selection in many loci as a new module for the landscape genetics programs, CDPOP and CDMetaPOP. Our module simulates multilocus selection using a linear additive model, providing a flexible platform to evaluate a wide range of genotype-environment associations. Importantly, the module allows simulation of selection in any number of loci under the influence of any number of environmental variables. We validated the module with individual-based selection simulations under Wright-Fisher assumptions. We then evaluated results for simulations under a simple landscape selection model. Next, we simulated individual-based multilocus selection across a complex selection landscape with three loci linked to three different environmental variables. Finally, we demonstrated how the program can be used to simulate multilocus selection under varying selection strengths across different levels of gene flow in a landscape genetics framework. This new module provides a valuable addition to the study of landscape genetics, allowing for explicit evaluation of the contributions and interactions between gene flow and selection-driven processes across complex, multivariate environmental and landscape conditions.

Purpose: Review scientific literature concerning femtosecond laser–assisted cataract surgery. Methods: Following databases were searched: CENTRAL (Cochrane Eyes and Vision Trials Register; Cochrane Library: Issue 2 of 12, June 2019), Ovid MEDLINE® without Revisions (1996 to June 2019), Ovid MEDLINE® (1946 to June 2019), Ovid MEDLINE® Daily Update June 2019, MEDLINE and MEDLINE Non-Indexed Items, Embase (1980–2019), Embase (1974 to June 2019), Ovid MEDLINE® and Epub Ahead of Print, in-Process & Other Non-Indexed Citations and Daily (1946 to June 2019), Web of Science (all years), the metaRegister of Controlled Trials ( www.controlled-trials.com ), ClinicalTrials.gov ( www.clinicaltrial.gov ) and World Health Organization International Clinical Trials Registry Platform ( www.who.int/ictrp/search/en ). Search terms/keywords included ‘Femtosecond laser’ combined with ‘cataract’, ‘cataract surgery’. Results: Based on quality of their methodology and their originality, 121 articles were reviewed, including randomised controlled trials, cohort studies, case-controlled studies, case series, case reports and laboratory studies. Each step of the femtosecond laser–assisted cataract surgery procedure (corneal incisions, arcuate keratotomies, capsulotomy and lens fragmentation) has been discussed with relevance to published outcomes, as well as complication rates of femtosecond laser–assisted cataract surgery, and what we can learn from the larger studies/meta-analyses and the economics of femtosecond laser–assisted cataract surgery within different healthcare settings. Conclusion: Studies suggest that the current clinical outcomes of femtosecond laser–assisted cataract surgery are not different to conventional phacoemulsification surgery and it is not cost effective when compared with conventional phacoemulsification surgery. In its current technological form, it is a useful surgical tool in specific complex cataract scenarios, but its usage has not been shown to translate into better clinical outcomes.

Fluorapophyllite-(Cs) (IMA 2018-108a), ideally CsCa4(Si8O20)F(H2O)8, is an apophyllite-group mineral from the moraine of the Darai-Pioz glacier, Tien-Shan, Northern Tajikistan. Associated minerals are quartz, pectolite, baratovite, aegirine, leucosphenite, pyrochlore, neptunite, fluorapophyllite-(K), and reedmergnerite. Fluorapophyllite-(Cs) is a hydrothermal mineral. It is colorless and has a vitreous luster and a white streak. Cleavage is perfect; it is brittle and has a stepped fracture. Mohs hardness is 4.5–5. Dmeas. = 2.54(2) g/cm3, Dcalc. = 2.513 g/cm3. Fluorapophyllite-(Cs) is unixial (+) with refractive indices (λ = 589 nm) ω = 1.540(2), ε = 1.544(2). It is non-pleochroic. Chemical analysis by electron microprobe gave SiO2 48.78, Al2O3 0.05, CaO 22.69, Cs2O 10.71, K2O 1.13, Na2O 0.04, F 1.86, H2Ocalc. 14.61, –O=F2 –0.78, sum 99.09 wt.%; H2O was calculated from crystal-structure analysis. The empirical formula based on 29 (O + F) apfu, H2O = 8 pfu, is (Cs0.75K0.24)Σ0.99(Ca3.99Na0.01)Σ4(Si8.01Al0.01)Σ8.02O20.03F0.97(H2O)8, Z = 2. The simplified formula is (Cs,K)(Ca,Na)4(Si,Al)8O20F(H2O)8. Fluorapophyllite-(Cs) is tetragonal, space group P4/mnc, a 9.060(6), c 15.741(11) Å, V 1292.10(19) Å3. The crystal structure has been refined to R1 = 4.31% based on 498 unique (Fo > 4σF) reflections. In the crystal structure of fluorapophyllite-(Cs), there is one [4]T site occupied solely by Si, = 1.615 Å. SiO4 tetrahedra link to form a (Si8O20)8– sheet perpendicular to [001]. Between the Si–O sheets, there are two cation sites: A and B. The A site is coordinated by eight H2O groups [O(4) site], A–O(4) = 3.152(4) Å; the A site contains Cs0.75K0.24□0.01, ideally Cs apfu. The Cs–O bond length of 3.152 Å is definitely larger than the K–O bond length of 2.966–2.971 Å in fluorapophyllite-(K), KCa4(Si8O20)F(H2O)8. The [7]B site contains Ca3.99Na0.01, ideally Ca4apfu; = 2.417 Å (φ = O, F, H2O). The Si–O sheets connect via A and B polyhedra and hydrogen bonding; two H atoms have been included in the refinement. Fluorapophyllite-(Cs) is isostructural with fluorapophyllite-(K). Fluorapophyllite-(Cs) is a Cs-analogue of fluorapophyllite-(K).

Inception has been proposed as a means to protect our cyber domain. In order to fully take advantage of this strategy we must first understand deception from the human point of view, because it is the human cyber attacker that plans and orchestrates cyberattacks. Moreover, although various deceptive tactics are addressed in the cyber-security literature, it appears they are categorized more from the standpoint of technology than from their behavioral origins. In order to better understand the interplay between attacker and defender, and associated cues of deception, we abstracted the cyber deception task. Participants played a modified version of Battleship either face-to-face or with a divider. Deception was significantly higher in the divider condition. Additionally, participants used patterns of deception analogous to cyber attackers and defenders such as blatant lies, diversion, and honeypots. An array of behavioral cues were also observed when participants lied and included variations in tone of voice, less eye contact, lower response time, and other physical indicators. Implications and future projects are discussed.

Here, we report the genome sequences of three bacterial isolates, Kinneretia sp. strain XES5, Shinella sp. strain XGS7, and Vogesella sp. strain XCS3, which were cultured from skin of adult female laboratory-bred Xenopus laevis .

Purpose Air pollution is associated with chronic diseases of later life. Cataract is the most common cause of blindess globally. It is biologically plausible that cataract risk is increased by pollution exposure. Therefore, the relationship between air pollution and incident cataract surgery was examined. Methods This was a prospective, observational study involving 433,727 UK Biobank participants. Ambient air pollution measures included particulates, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Outdoor air pollution was estimated based on land use regression models. Participants undergoing cataract surgery in either eye were ascertained via data linkage to the National Health Service procedure statistics. Those undergoing cataract surgery within 1 year of baseline assessment and those reporting cataract at baseline were excluded. Cox proportional hazards models were used to examine the associations between air pollutants and incident cataract surgery, adjusting for sociodemographic and lifestyle factors. Results There were 16,307 incident cases of cataract surgery. Higher exposure to PM2.5 was associated with a 5% increased risk of incident cataract surgery (per interquartile range [IQR] increase). Compared to the lowest quartile, participants with exposures to PM2.5, NO2, and NOx in the highest quartile were 14%, 11%, and 9% more likely to undergo cataract surgery, respectively. A continuous exposure-response relationship was observed, with the likelihood of undergoing cataract surgery being progressively higher with greater levels of PM2.5, NO2, and NOx (P for trend P < 0.001). Conclusions Although the results of our study showed a 5% increased risk of future cataract surgery following an exposure to PM2.5, NO2, and NOx, the effect estimates were relatively small. Further research is required to determine if the associations identified are causal.

The diversity of multicellular organisms is, in large part, due to the fact that multicellularity has independently evolved many times. Nonetheless, multicellular organisms all share a universal biophysical trait: cells are attached to each other. All mechanisms of cellular attachment belong to one of two broad classes; intercellular bonds are either reformable or they are not. Both classes of multicellular assembly are common in nature, having independently evolved dozens of times. In this review, we detail these varied mechanisms as they exist in multicellular organisms. We also discuss the evolutionary implications of different intercellular attachment mechanisms on nascent multicellular organisms. The type of intercellular bond present during early steps in the transition to multicellularity constrains future evolutionary and biophysical dynamics for the lineage, affecting the origin of multicellular life cycles, cell–cell communication, cellular differentiation, and multicellular morphogenesis. The types of intercellular bonds used by multicellular organisms may thus result in some of the most impactful historical constraints on the evolution of multicellularity.

It has been 20 months since we first heard of SARS-CoV-2, the novel coronavirus detected in the Hubei province, China, in December 2019, responsible for the ongoing COVID-19 pandemic. Since then, a myriad of studies aimed at understanding and controlling SARS-CoV-2 have been published at a pace that has outshined the original effort to combat HIV during the beginning of the AIDS epidemic. This massive response started by developing strategies to not only diagnose individual SARS-CoV-2 infections but to monitor the transmission, evolution, and global spread of this new virus. We currently have hundreds of commercial diagnostic tests, however, that was not the case in early 2020, when just a handful of protocols were available, and few whole-genome SARS-CoV-2 sequences had been described. It was mid-January 2020 when several District Health Boards across New Zealand started planning the implementation of diagnostic testing for this emerging virus. Here, we describe our experience implementing a molecular test to detect SARS-CoV-2 infection, adapting the RT-qPCR assay to be used in a random-access platform (Hologic Panther Fusion® System) in a clinical laboratory, and characterizing the first whole-genome SARS-CoV-2 sequences obtained in the South Island, right at the beginning of the SARS-CoV-2 outbreak in New Zealand. We expect that this work will help us and others prepare for the unequivocal risk of similar viral outbreaks in the future.

The influence of large‐scale variables such as climate change on phenology has received a great deal of research attention. However, local environmental factors also play a key role in determining the timing of species life cycles. Using the meadow brown butterfly Maniola jurtina as an example, we investigate how a specific habitat type, lowland calcareous grassland, can affect the timing of flight dates. Although protracted flight periods have previously been reported in populations on chalk grassland sites in the south of England, no attempt has yet been made to quantify this at a national level, or to assess links with population genetics and drought tolerance. Using data from 539 sites across the UK, these differences in phenology are quantified, and M. jurtina phenology is found to be strongly associated with both site geology and topography, independent of levels of abundance. Further investigation into aspects of M. jurtina ecology at a subset of sites finds no genetic structuring or drought tolerance associated with these same site conditions., Maniola jurtina phenology is found to be strongly associated with both site geology and topography, independent of mean abundance across 539 monitoring sites. Across a subset of sites, no genetic structuring was associated with these site characteristics. Populations displayed high levels of genetic diversity but low genetic differentiation. Across a subset of sites, drought tolerance was not associated with site geology.

DNA methylation is a key epigenetic modification implicated in the pathogenesis of numerous human diseases, including cancer development and metastasis. Gene promoter methylation changes are widely associated with transcriptional deregulation and disease progression. The advent of CRISPR-based technologies has provided a powerful toolkit for locus-specific manipulation of the epigenome. Here, we describe a comprehensive global workflow for the design and application of a dCas9-SunTag-based tool for editing a DNA methylation locus in human melanoma cells, alongside protocols for downstream techniques used to evaluate subsequent methylation and gene expression changes in methylation-edited cells. Using transient system delivery, we demonstrate both highly efficacious methylation and demethylation of the EBF3 promoter, a putative epigenetic driver of melanoma metastasis, achieving up to 304.00% gain of methylation and 99.99% relative demethylation, respectively. Further, we employ a novel, targeted screening approach to confirm minimal off-target activity and high on-target specificity of our editing sys-tem within our target locus.

Marine Protected Areas (MPAs) are conservation tools intended to protect biodiversity, promote healthy and resilient marine ecosystems, and provide societal benefits. Despite codification of MPAs in international agreements, MPA effectiveness is currently undermined by confusion about the many MPA types and consequent wildly differing outcomes. We present a clarifying science-driven framework—The MPA Guide—to aid design and evaluation. The guide categorizes MPAs by stage of establishment and level of protection, specifies the resulting direct and indirect outcomes for biodiversity and human well-being, and describes the key conditions necessary for positive outcomes. Use of this MPA Guide by scientists, managers, policy-makers, and communities can improve effective design, implementation, assessment, and tracking of existing and future MPAs to achieve conservation goals by using scientifically grounded practices.

To inform cost-effective monitoring of offshore geological storage of carbon dioxide (CO 2), a unique field experiment, designed to simulate leakage of CO 2 from a sub-seafloor storage reservoir, was carried out in the central North Sea. A total of 675 kg of CO 2 were released into the shallow sediments (∼3 m below seafloor) for 11 days at flow rates between 6 and 143 kg d -1. A set of natural, inherent tracers ( 13C, 18O) of injected CO 2 and added, non-toxic tracer gases (octafluoropropane, sulfur hexafluoride, krypton, methane) were used to test their applicability for CO 2 leakage attribution and quantification in the marine environment. All tracers except 18O were capable of attributing the CO 2 source. Tracer analyses indicate that CO 2 dissolution in sediment pore waters ranged from 35 % at the lowest injection rate to 41% at the highest injection rate. Direct measurements of gas released from the sediment into the water column suggest that 22 % to 48 % of the injected CO 2 exited the seafloor at, respectively, the lowest and the highest injection rate. The remainder of injected CO 2 accumulated in gas pockets in the sediment. The methodologies can be used to rapidly confirm the source of leaking CO 2 once seabed samples are retrieved.

In recent years, gravitational wave observatories have conquered the world science scene due to their unprecedented capability to observe astrophysical signals. Those first observations opened up multimessenger astronomy and called for a tremendous R effort to improve the sensitivity of future detectors. One of the many issues to be solved, not to affect the desired sensitivity, is the noise induced by the use of room temperature mirrors, especially for the low-frequency detection range. The use of cryogenic mirrors to reduce such a noise source has been individuated as a viable solution to obtain the desired sensitivity at low frequency. Cryogenically cooled mirrors, routinely operating at 10 K, present a number of extraordinary challenges, one being the cryogenic vacuum system hosting the cold mirrors. Gases composing the residual vacuum will tend to cryosorb and build a contaminant ice layer (``frost'') on the mirror surface. Depending on such ice layer thickness, various unwanted detrimental effects may occur affecting mirror performances. This paper analyzes the consequences of hosting a cryogenically cooled mirror in a vacuum system and sets new limits for an acceptable operating pressure to avoid frost formation in a given period of continuous data taking. Since ice formation can be reduced but not avoided, we analyze potential mitigation methods to cure such a phenomenon. Thermal and nonthermal methods are analyzed and compared. Electron stimulated desorption is also considered as an alternative method to desorb the ice layer on mirrors. Finally, we briefly discuss further studies needed to validate the various methods with special care on their effects on the mirror perfection and optical properties.

While early multicellular lineages necessarily started out as relatively simple groups of cells, little is known about how they became Darwinian entities capable of open-ended multicellular adaptation1,2. To explore this, we initiated the Multicellularity Long Term Evolution Experiment (MuLTEE), selecting for larger group size in the snowflake yeast (Saccharomyces cerevisiae) model system. Given the historical importance of oxygen limitation3, our ongoing experiment consists of three metabolic treatments4: anaerobic, obligately aerobic, and mixotrophic yeast. After 600 rounds of selection, snowflake yeast in the anaerobic treatment evolved to be macroscopic, becoming ~2·104times larger (~mm scale) and ~104-fold more biophysically tough, while retaining a clonal multicellular life cycle. They accomplished this through sustained biophysical adaptation, evolving increasingly elongate cells that initially reduced the strain of cellular packing, then facilitated branch entanglements that enabled groups of cells to stay together even after many cellular bonds fracture. In contrast, snowflake yeast competing for low oxygen remained microscopic, evolving to be just ~6-fold larger, underscoring the critical role of oxygen levels in the evolution of multicellular size. Taken together, this work provides unique insight into an ongoing evolutionary transition in individuality, showing how simple groups of cells overcome fundamental biophysical limitations via gradual, yet sustained, multicellular adaptation.