Nature contents: 14 August 2014

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Volume 512 Number 7513      nature •Visit Nature homepage •Subscribe to Nature •View Table of Contents The science that matters. Every week.               APPLY TODAY for the 2014 ONCOLOGY RESEARCH GRANT.  Together with Illumina, we're giving two deserving researchers the power to tap into the wealth of genomic data locked within FFPE samples using an innovative technique developed by EA | Quintiles using Illumina's RNA Access method. Unleash the power of your research with RNA-seq and DNA Methylation. expressionanalysis.com/grant       Jump to the content that matters to you View Table of Contents ▶ ▼ News & Comment   ▼ Biological Sciences   ▼ Health Sciences   ▼ Physical Sciences   ▼ Earth & Environmental Sciences   ▼ Careers & Jobs       This week's highlights     Biological Sciences More Biological sciences ▼   Neuropsychosocial profiles of current and future adolescent alcohol misusers   Many factors contribute to risk of alcohol abuse but their relative importance is difficult to quantify. Robert Whelan et al. constructed models of current and future adolescent binge drinking using data from the IMAGEN project, a study of risk-taking behaviour in over 2,000 teenagers recruited at age 14 from the United Kingdom, Ireland, France and Germany. A key finding is that personality factors are – surprisingly – not particularly useful predictors of future alcohol misuse. But neurodevelopmental immaturity, functional indicators in the brain, sexual experience and prenatal alcohol exposure are associated with current and future binge drinking.       Physical Sciences More Physical sciences ▼   Limits on fundamental limits to computation   Computers have evolved at a remarkable rate for fifty years, roughly in line with Gordon Moore's prediction that the number of transistors in a dense integrated circuit would double approximately every two years. The rate of 'Moore scaling' is slowing down and other physical limits are looming, but new technologies are on the way. In this Review Igor Markov takes a fresh look at the fundamental limits at various levels, from device to complete system levels. He argues that the study of the limits of fundamental limits to computation can lead to new insights for emerging technologies.       Earth & Environmental Sciences More Earth & Environmental sciences ▼   Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA   Human populations living in the Tibetan uplands have had many thousands of years to adapt to life at a high altitude. The hypoxia pathway gene EPAS1 was shown previously to be associated with this adaptation. This study of the DNA sequence of the chromosomal region around EPAS1 in Tibetan and Han Chinese individuals has arrived at a surprising and important result. The unusual haplotype structure of the Tibetan individuals appears to have been due to the introduction of DNA from Denisovans, a Homo species or subspecies known from a few high-altitude fossil discoveries in Siberia.           An Atlas of Genetic Influences on Human Blood Metabolites "Metabolomics...an excellent way of understanding individual uniqueness and..." - Craig Venter A new publication in Nature Genetics reveals how metabolomic profiling coupled with genomics data yields new insight into diseases, potential biomarkers and drug treatments. Freely available here.            Podcast & Video     In this week's podcast: piles of rubble in space, a caution about epigenetics, pregnancy and blame, and the anatomy of an earthquake.         News & Comment Read daily news coverage▶ ▲top               THIS WEEK           Editorials                   Save the children ▶     Infants and young people are being traumatized by armed conflict in their countries. Their resulting mental illnesses must be addressed, for the good of both the individuals and their society.             Future computing ▶     Pushing the boundaries of current computing technologies will show the way to new ones.             World View                   China should aim for a total cap on emissions ▶     A focus on carbon intensity alone will allow emissions to grow with the economy, argues Qiang Wang.             Seven Days                   Seven days: 8–14 August 2014 ▶     The week in science: Ebola declared an international public-health emergency; power-cut at UK’s Antarctic research station; and Rosetta space probe catches up with a comet.             NEWS IN FOCUS           Native ecosystems blitzed by drought ▶     California’s current water crisis offers a preview of what climate change will bring.             Health check for deep-sea mining ▶     European project evaluates risks to delicate ecosystems.             Teen drug use gets supersize study ▶     US government programme will examine 10,000 adolescents to document effects on developing brains.             US assesses virus of the Caribbean ▶     Researchers warn that a change of mosquito host could accelerate spread of chikungunya across the Americas.             Feature                   Online collaboration: Scientists and the social network ▶     Giant academic social networks have taken off to a degree that no one expected even a few years ago. A Nature survey explores why.             COMMENT           Society: Don't blame the mothers ▶     Careless discussion of epigenetic research on how early life affects health across generations could harm women, warn Sarah S. Richardson and colleagues.             Books and Arts                   History of engineering: Wonder maker ▶     Andrew Robinson delves into a study inspired by James Watt's fascinating workshop.             Books in brief ▶     Barbara Kiser reviews five of the week’s best science picks.             Correspondence                   Centenary: Russian stamp to honour physicist Renad I. Zhdanov, Pascal Chardonnet | Conservation: White possums must stay cool to survive William F. Laurance, Susan Laurance, Christine Milne | Transgenic crops: Mexican GM maize rift is not so simple Hugo Perales | Sexual harassment: Create ethics codes to curb sex abuse Margaret C. Hardy                 Nature Outlook Assessing Science   Australia and New Zealand might be neighbours, but their programmes of research assessment are very different. Focusing on the tools and methods used to measure the quality and impact of science in Australia and New Zealand should inform similar debates throughout the scientific world.   Access the Outlook free online for six months.          Biological Sciences ▲top             RESEARCH           Latest Online                   Developmental biology: It takes muscle to make blood cells ▶     Suphansa Sawamiphak, Didier Y. R. Stainier             Immunology: Mammalian watchdog targets bacteria ▶     Parag Kundu, Sven Pettersson             AhR sensing of bacterial pigments regulates antibacterial defence ▶     Pedro Moura-Alves, Kellen Faé, Erica Houthuys et al.     The mammalian aryl hydrocarbon receptor (known to sense environmental pollutants) is shown to also have a role as a pattern recognition receptor in sensing bacterial virulence factors, resulting in an antibacterial response and activation of innate and natural defences.             PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies ▶     Thomas De Raedt, Eline Beert, Eric Pasmant et al.     SUZ12, a component of the PRC2 complex, can also function as a tumour suppressor in certain tumours of the nervous system and melanomas.             Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5′-diphosphates ▶     Delphine Goubau, Martin Schlee, Safia Deddouche et al.     The innate immune receptor RIG-I is shown to sense 5′-diphosphate RNAs as found in some viral genomes in addition to its well characterized activation by RNAs bearing 5′-triphosphate moieties.             A long noncoding RNA protects the heart from pathological hypertrophy ▶     Pei Han, Wei Li, Chiou-Hong Lin et al.     Here, a long noncoding RNA, termed Mhrt, is identified in the loci of myosin heavy chain (Myh) genes in mice and shown to be capable of suppressing cardiomyopathy in the animals, as well as being repressed in diseased human hearts.             Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function ▶     Andrea Viale, Piergiorgio Pettazzoni, Costas A. Lyssiotis et al.     KRAS mutations are a driver event of pancreatic ductal adenocarcinoma; here, a subpopulation of dormant tumour cells, relying on oxidative phosphorylation for survival, is shown to be responsible for tumour relapse after treatment targeting the KRAS pathway.             Enhanced neonatal Fc receptor function improves protection against primate SHIV infection ▶     Sung-Youl Ko, Amarendra Pegu, Rebecca S. Rudicell et al.     A mutation in VRC01, a broadly neutralizing, HIV-1-specific antibody, confers enhanced binding to the neonatal Fc receptor, increasing the antibody half-life in the serum and localization in mucosal tissues, where it provides superior protection against rectal simian HIV-1 infection in macaques.             Jam1a–Jam2a interactions regulate haematopoietic stem cell fate through Notch signalling ▶     Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim et al.     Notch signalling has a key role in the generation of haematopoietic stem cells (HSCs) during vertebrate development; here two adhesion molecules, Jam1a and Jam2a, are shown to be essential for the contact between precursors of HSCs and the somite during embryonic migration, and the Jam1a–Jam2a interaction is shown to be needed to transmit the Notch signal and produce HSCs.             Haematopoietic stem cell induction by somite-derived endothelial cells controlled by meox1 ▶     Phong Dang Nguyen, Georgina Elizabeth Hollway, Carmen Sonntag et al.     A new somite compartment, called the endotome, that contributes to the formation of the embryonic dorsal aorta by providing endothelial progenitors is identified here; endotome-derived endothelial progenitors, whose formation is regulated by the activity of the meox1 gene, induce haematopoietic stem cell formation upon colonization of the nascent dorsal aorta.             Piezo1 integration of vascular architecture with physiological force ▶     Jing Li, Bing Hou, Sarka Tumova et al.     The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development.             Crystal structure of the RNA-guided immune surveillance Cascade complex in Escherichia coli ▶     Hongtu Zhao, Gang Sheng, Jiuyu Wang et al.     The CRISPR/Cas system is an RNA-guided bacterial protection system against foreign nucleic acids of bacterial and archaeal origin; here a high-resolution crystal structure of the CRIPSR RNA–Cas complex shows that the CRIPSR RNA plays an essential role not only in target recognition but also in complex assembly.             Articles and Letters                   Clonal evolution in breast cancer revealed by single nucleus genome sequencing ▶     Yong Wang, Jill Waters, Marco L. Leung et al.     To investigate genomic diversity within tumours, a new type of whole-genome and exome single cell sequencing has been developed using G2/M nuclei; the technique was used to sequence single nuclei from an oestrogen-positive breast cancer and a triple-negative ductal carcinoma—aneuploidy rearrangements emerged as early events in tumour formation and then point mutations evolved gradually over time.             Crystal structure of the human COP9 signalosome ▶     Gondichatnahalli M. Lingaraju, Richard D. Bunker, Simone Cavadini et al.     The COP9 signalosome (CSN) complex regulates cullin–RING E3 ubiquitin ligases—the largest class of ubiquitin ligase enzymes, which are involved in a multitude of regulatory processes; here, the crystal structure of the entire human CSN holoenzyme is presented.             Three-dimensional structure of human γ-secretase ▶     Peilong Lu, Xiao-chen Bai, Dan Ma et al.     The three-dimensional structure of intact human γ-secretase complex at 4.5 Å resolution is revealed by cryo-electron-microscopy single-particle analysis; the complex comprises a horseshoe-shaped transmembrane domain containing 19 transmembrane segments, and a large extracellular domain from nicastrin, which sits immediately above the hollow space formed by the horseshoe.             Neuropsychosocial profiles of current and future adolescent alcohol misusers ▶     Robert Whelan, Richard Watts, Catherine A. Orr et al.     Many factors have been proposed as contributors to risk of alcohol abuse, but quantifying their influence has been difficult; here a longitudinal study of a large sample of adolescents and machine learning are used to generate models of predictors of current and future alcohol abuse, assessing the relative contribution of many factors, including life history, individual personality differences, brain structure and genotype.             A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes ▶     Ida Moltke, Niels Grarup, Marit E. Jørgensen et al.     An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits.             Altitude adaptation in Tibetans caused by introgression of Denisovan-like DNA ▶     Emilia Huerta-Sánchez, Xin Jin, Asan et al.     Admixture with other hominin species helped humans to adapt to high-altitude environments; the EPAS1 gene in Tibetan individuals has an unusual haplotype structure that probably resulted from introgression of DNA from Denisovan or Denisovan-related individuals into humans, and this haplotype is only found in Denisovans and Tibetans, and at low frequency among Han Chinese.             Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells ▶     Johanna Flach, Sietske T. Bakker, Mary Mohrin et al.     Haematopoietic stem cell (HSC) function is known to degrade with age; here, replication stress is shown to be a potent driver of the functional decline of HSCs during physiological ageing in mice due to decreased expression of mini-chromosome maintenance helicase components and reduced activity of the DNA replication machinery.             Historical contingency and its biophysical basis in glucocorticoid receptor evolution ▶     Michael J. Harms, Joseph W. Thornton     By characterizing a very large number of might-have-been evolutionary trajectories starting from a resurrected ancestral protein, the authors show that the evolution of an essential modern protein was contingent on extremely unlikely historical mutations.             DENR–MCT-1 promotes translation re-initiation downstream of uORFs to control tissue growth ▶     Sibylle Schleich, Katrin Strassburger, Philipp Christoph Janiesch et al.     This study identifies the DENR–MCT-1 complex as the first factors in animals specific for translation re-initiation downstream of upstream Open Reading Frames (uORFs).             Histone H4 tail mediates allosteric regulation of nucleosome remodelling by linker DNA ▶     William L. Hwang, Sebastian Deindl, Bryan T. Harada et al.     A nucleosome-spacing mechanism for human ATP-dependent chromatin assembly and remodelling factor (ACF).             Visualization of arrestin recruitment by a G-protein-coupled receptor ▶     Arun K. Shukla, Gerwin H. Westfield, Kunhong Xiao et al.     Single-particle electron microscopy and hydrogen–deuterium exchange mass spectrometry are used to characterize the structure and dynamics of a G-protein-coupled receptor–arrestin complex.             News & Views                   Neuroscience: What females really want ▶     Leslie C. Griffith             Ageing: Old blood stem cells feel the stress ▶     Jiri Bartek, Zdenek Hodny             Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb             Structural biology: Corralling a protein-degradation regulator ▶     Raymond J. Deshaies             Developmental biology: It takes muscle to make blood cells ▶     Suphansa Sawamiphak, Didier Y. R. Stainier             Immunology: Mammalian watchdog targets bacteria ▶     Parag Kundu, Sven Pettersson             Research Highlights                   Gene editing: CRISPR corrects β-thalassaemia | Microbiology: Resistance genes mapped | Imaging: Seeing through a mouse skull | Stem cells: Fresh growth from elderly cells | Microbiology: Ecosystems afloat in asphalt         NEWS & COMMENT           Society: Don't blame the mothers | Conservation: White possums must stay cool to survive | Save the children | Native ecosystems blitzed by drought | Teen drug use gets supersize study | US assesses virus of the Caribbean             More Biological Sciences ▶                     Health Sciences ▲top             RESEARCH           Latest Online                   PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies ▶     Thomas De Raedt, Eline Beert, Eric Pasmant et al.     SUZ12, a component of the PRC2 complex, can also function as a tumour suppressor in certain tumours of the nervous system and melanomas.             A long noncoding RNA protects the heart from pathological hypertrophy ▶     Pei Han, Wei Li, Chiou-Hong Lin et al.     Here, a long noncoding RNA, termed Mhrt, is identified in the loci of myosin heavy chain (Myh) genes in mice and shown to be capable of suppressing cardiomyopathy in the animals, as well as being repressed in diseased human hearts.             Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function ▶     Andrea Viale, Piergiorgio Pettazzoni, Costas A. Lyssiotis et al.     KRAS mutations are a driver event of pancreatic ductal adenocarcinoma; here, a subpopulation of dormant tumour cells, relying on oxidative phosphorylation for survival, is shown to be responsible for tumour relapse after treatment targeting the KRAS pathway.             Piezo1 integration of vascular architecture with physiological force ▶     Jing Li, Bing Hou, Sarka Tumova et al.     The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development.             Articles and Letters                   Clonal evolution in breast cancer revealed by single nucleus genome sequencing ▶     Yong Wang, Jill Waters, Marco L. Leung et al.     To investigate genomic diversity within tumours, a new type of whole-genome and exome single cell sequencing has been developed using G2/M nuclei; the technique was used to sequence single nuclei from an oestrogen-positive breast cancer and a triple-negative ductal carcinoma—aneuploidy rearrangements emerged as early events in tumour formation and then point mutations evolved gradually over time.             Three-dimensional structure of human γ-secretase ▶     Peilong Lu, Xiao-chen Bai, Dan Ma et al.     The three-dimensional structure of intact human γ-secretase complex at 4.5 Å resolution is revealed by cryo-electron-microscopy single-particle analysis; the complex comprises a horseshoe-shaped transmembrane domain containing 19 transmembrane segments, and a large extracellular domain from nicastrin, which sits immediately above the hollow space formed by the horseshoe.             Neuropsychosocial profiles of current and future adolescent alcohol misusers ▶     Robert Whelan, Richard Watts, Catherine A. Orr et al.     Many factors have been proposed as contributors to risk of alcohol abuse, but quantifying their influence has been difficult; here a longitudinal study of a large sample of adolescents and machine learning are used to generate models of predictors of current and future alcohol abuse, assessing the relative contribution of many factors, including life history, individual personality differences, brain structure and genotype.             A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes ▶     Ida Moltke, Niels Grarup, Marit E. Jørgensen et al.     An association mapping study of type-2-diabetes-related quantitative traits in the Greenlandic population identified a common variant in TBC1D4 that increases plasma glucose levels and serum insulin levels after an oral glucose load and type 2 diabetes risk, with effect sizes several times larger than any previous findings of large-scale genome-wide association studies for these traits.             News & Views                   Cancer: One cell at a time ▶     Edward J. Fox, Lawrence A. Loeb           NEWS & COMMENT           Society: Don't blame the mothers | Save the children | Teen drug use gets supersize study | US assesses virus of the Caribbean             More Health Sciences ▶               Physical Sciences ▲top             RESEARCH           Latest Online                   Interacting supernovae from photoionization-confined shells around red supergiant stars ▶     Jonathan Mackey, Shazrene Mohamed, Vasilii V. Gvaramadze et al.     A model in which the stellar wind of the fast-moving red supergiant Betelgeuse is photoionized by radiation from external sources can explain the dense, almost static shell recently discovered around the star, and predicts both that debris from Betelgeuse’s eventual supernova explosion will violently collide with the shell and that other red supergiants should have similar, but much more massive, shells.             Articles and Letters                   The origin of the local 1/4-keV X-ray flux in both charge exchange and a hot bubble ▶     M. Galeazzi, M. Chiao, M. R. Collier et al.     The contribution of solar-wind ions exchanging electrons with helium and hydrogen near the Sun is shown to be only about 40 per cent of the 1/4-keV X-ray flux observed in the Galactic plane; this supports the existence of a local ‘hot bubble’ filled with X-ray-emitting gas, accounting for the rest of the flux.             Cohesive forces prevent the rotational breakup of rubble-pile asteroid (29075) 1950 DA ▶     Ben Rozitis, Eric MacLennan, Joshua P. Emery     Modelling and observations of the kilometre-sized asteroid (29075) 1950 DA reveal it to be a ‘rubble pile’ that is rotating faster than is allowed by gravity and friction; cohesive forces such as those in lunar regolith are required to prevent it breaking up.             Formation of monatomic metallic glasses through ultrafast liquid quenching ▶     Li Zhong, Jiangwei Wang, Hongwei Sheng et al.     Metallic liquids of single elements have been successfully vitrified to their glassy states by achieving an ultrafast quenching rate in a new experimental design, of which the process has been monitored and studied by a combination of in situ transmission electron microscopy and atoms-to-continuum computer modelling.             The tidal–rotational shape of the Moon and evidence for polar wander ▶     Ian Garrick-Bethell, Viranga Perera, Francis Nimmo et al.     Analysis of the Moon's topography reveals that when its largest basins are removed, the lunar shape is consistent with processes controlled by early Earth tides, and implies a reorientation of the Moon's principal shape axes.             Reviews and Perspectives                   Limits on fundamental limits to computation ▶     Igor L. Markov     To evaluate the promise of potential computing technologies, this review examines a wide range of fundamental limits, such as to performance, power consumption, size and cost, from the device level to the system level.             News & Views                   Solar system: Sandcastles in space ▶     Daniel J. Scheeres             Condensed-matter physics: Glasses made from pure metals ▶     Jan Schroers             Astronomical instrumentation: Atmospheric blurring has a new enemy ▶     Brent Ellerbroek             Research Highlights                   Astronomy: Another super-Earth found | Chemistry: Cleaner, greener ammonia | Social selection: Clash over the Kardashians of science         NEWS & COMMENT           Future computing | History of engineering: Wonder maker | Centenary: Russian stamp to honour physicist             More Physical Sciences ▶               Earth & Environmental Sciences ▲top             RESEARCH           Latest Online                   Earth science: Warning signs of the Iquique earthquake ▶     Roland Bürgmann             Abrupt glacial climate shifts controlled by ice sheet changes ▶     Xu Zhang, Gerrit Lohmann, Gregor Knorr et al.     The volume of the Northern Hemisphere ice sheet controlled abrupt millennial-scale climate changes during the last glacial.             Continuing megathrust earthquake potential in Chile after the 2014 Iquique earthquake ▶     Gavin P. Hayes, Matthew W. Herman, William D. Barnhart et al.     The 2014 Iquique event was not the earthquake that had been expected to fill the regional seismic gap; given that significant sections of the northern Chile subduction zone have not ruptured in almost 150 years, it is likely that future megathrust earthquakes will occur south and potentially north of the 2014 Iquique sequence.             Gradual unlocking of plate boundary controlled initiation of the 2014 Iquique earthquake ▶     Bernd Schurr, Günter Asch, Sebastian Hainzl et al.     A long foreshock series unlocked the South American plate boundary until eventually initiating the M 8.1 Iquique, Chile, earthquake.             Articles and Letters                   The tidal–rotational shape of the Moon and evidence for polar wander ▶     Ian Garrick-Bethell, Viranga Perera, Francis Nimmo et al.     Analysis of the Moon's topography reveals that when its largest basins are removed, the lunar shape is consistent with processes controlled by early Earth tides, and implies a reorientation of the Moon's principal shape axes.         Interacting supernovae from photoionization-confined shells around red supergiant stars ▶     Jonathan Mackey, Shazrene Mohamed, Vasilii V. Gvaramadze et al.     A model in which the stellar wind of the fast-moving red supergiant Betelgeuse is photoionized by radiation from external sources can explain the dense, almost static shell recently discovered around the star, and predicts both that debris from Betelgeuse’s eventual supernova explosion will violently collide with the shell and that other red supergiants should have similar, but much more massive, shells.             News & Views                   Solar system: Sandcastles in space ▶     Daniel J. Scheeres             Astronomical instrumentation: Atmospheric blurring has a new enemy ▶     Brent Ellerbroek             Earth science: Warning signs of the Iquique earthquake ▶     Roland Bürgmann             Research Highlights                   Polar science: Arctic snowpack thins | Seismology: From earthquakes to icequakes         NEWS & COMMENT           Health check for deep-sea mining | Books in brief | Conservation: White possums must stay cool to survive | Native ecosystems blitzed by drought             More Earth & Environmental Sciences ▶                 Scientific Data: Now Live  Scientific Data is an open-access, peer-reviewed publication and exists to help you publish, discover and reuse research data. It is now live so go visit nature.com/scientificdata to discover more and view our Data Descriptors.         Careers & Jobs ▲top               Mental health: Stressed students reach out for help ▶     Graduate students struggling with the stresses of their work and lives can tap into multiple avenues of support.             Careers related news & comment                   Online collaboration: Scientists and the social network Richard Van Noorden | Sexual harassment: Create ethics codes to curb sex abuse Margaret C. Hardy | Seven days: 8–14 August 2014               naturejobs.com Science jobs of the week       Postdoctoral research opportunity     Umeå University            Research Technician     University of Edinburgh            Post-Doctoral Research Associate     Georgia State University            Research Associate     Imperial College London          No matter what your career stage, student, postdoc or senior scientist, you will find articles on naturejobs.com to help guide you in your science career. Keep up-to-date with the latest sector trends, vote in our reader poll and sign-up to receive the monthly Naturejobs newsletter.           • Natureevents Directory featured events           natureevents directory featured events         Development of Cancer Medicines     27.11.14 London, UK         Natureevents Directory is the premier resource for scientists looking for the latest scientific conferences, courses, meetings and symposia. 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