ALBERT

Description: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Multiple Sclerosis Genetics Consortium -- Wellcome Trust Case Control Consortium 2 -- Sawcer, Stephen -- Hellenthal, Garrett -- Pirinen, Matti -- Spencer, Chris C A -- Patsopoulos, Nikolaos A -- Moutsianas, Loukas -- Dilthey, Alexander -- Su, Zhan -- Freeman, Colin -- Hunt, Sarah E -- Edkins, Sarah -- Gray, Emma -- Booth, David R -- Potter, Simon C -- Goris, An -- Band, Gavin -- Oturai, Annette Bang -- Strange, Amy -- Saarela, Janna -- Bellenguez, Celine -- Fontaine, Bertrand -- Gillman, Matthew -- Hemmer, Bernhard -- Gwilliam, Rhian -- Zipp, Frauke -- Jayakumar, Alagurevathi -- Martin, Roland -- Leslie, Stephen -- Hawkins, Stanley -- Giannoulatou, Eleni -- D'alfonso, Sandra -- Blackburn, Hannah -- Martinelli Boneschi, Filippo -- Liddle, Jennifer -- Harbo, Hanne F -- Perez, Marc L -- Spurkland, Anne -- Waller, Matthew J -- Mycko, Marcin P -- Ricketts, Michelle -- Comabella, Manuel -- Hammond, Naomi -- Kockum, Ingrid -- McCann, Owen T -- Ban, Maria -- Whittaker, Pamela -- Kemppinen, Anu -- Weston, Paul -- Hawkins, Clive -- Widaa, Sara -- Zajicek, John -- Dronov, Serge -- Robertson, Neil -- Bumpstead, Suzannah J -- Barcellos, Lisa F -- Ravindrarajah, Rathi -- Abraham, Roby -- Alfredsson, Lars -- Ardlie, Kristin -- Aubin, Cristin -- Baker, Amie -- Baker, Katharine -- Baranzini, Sergio E -- Bergamaschi, Laura -- Bergamaschi, Roberto -- Bernstein, Allan -- Berthele, Achim -- Boggild, Mike -- Bradfield, Jonathan P -- Brassat, David -- Broadley, Simon A -- Buck, Dorothea -- Butzkueven, Helmut -- Capra, Ruggero -- Carroll, William M -- Cavalla, Paola -- Celius, Elisabeth G -- Cepok, Sabine -- Chiavacci, Rosetta -- Clerget-Darpoux, Francoise -- Clysters, Katleen -- Comi, Giancarlo -- Cossburn, Mark -- Cournu-Rebeix, Isabelle -- Cox, Mathew B -- Cozen, Wendy -- Cree, Bruce A C -- Cross, Anne H -- Cusi, Daniele -- Daly, Mark J -- Davis, Emma -- de Bakker, Paul I W -- Debouverie, Marc -- D'hooghe, Marie Beatrice -- Dixon, Katherine -- Dobosi, Rita -- Dubois, Benedicte -- Ellinghaus, David -- Elovaara, Irina -- Esposito, Federica -- Fontenille, Claire -- Foote, Simon -- Franke, Andre -- Galimberti, Daniela -- Ghezzi, Angelo -- Glessner, Joseph -- Gomez, Refujia -- Gout, Olivier -- Graham, Colin -- Grant, Struan F A -- Guerini, Franca Rosa -- Hakonarson, Hakon -- Hall, Per -- Hamsten, Anders -- Hartung, Hans-Peter -- Heard, Rob N -- Heath, Simon -- Hobart, Jeremy -- Hoshi, Muna -- Infante-Duarte, Carmen -- Ingram, Gillian -- Ingram, Wendy -- Islam, Talat -- Jagodic, Maja -- Kabesch, Michael -- Kermode, Allan G -- Kilpatrick, Trevor J -- Kim, Cecilia -- Klopp, Norman -- Koivisto, Keijo -- Larsson, Malin -- Lathrop, Mark -- Lechner-Scott, Jeannette S -- Leone, Maurizio A -- Leppa, Virpi -- Liljedahl, Ulrika -- Bomfim, Izaura Lima -- Lincoln, Robin R -- Link, Jenny -- Liu, Jianjun -- Lorentzen, Aslaug R -- Lupoli, Sara -- Macciardi, Fabio -- Mack, Thomas -- Marriott, Mark -- Martinelli, Vittorio -- Mason, Deborah -- McCauley, Jacob L -- Mentch, Frank -- Mero, Inger-Lise -- Mihalova, Tania -- Montalban, Xavier -- Mottershead, John -- Myhr, Kjell-Morten -- Naldi, Paola -- Ollier, William -- Page, Alison -- Palotie, Aarno -- Pelletier, Jean -- Piccio, Laura -- Pickersgill, Trevor -- Piehl, Fredrik -- Pobywajlo, Susan -- Quach, Hong L -- Ramsay, Patricia P -- Reunanen, Mauri -- Reynolds, Richard -- Rioux, John D -- Rodegher, Mariaemma -- Roesner, Sabine -- Rubio, Justin P -- Ruckert, Ina-Maria -- Salvetti, Marco -- Salvi, Erika -- Santaniello, Adam -- Schaefer, Catherine A -- Schreiber, Stefan -- Schulze, Christian -- Scott, Rodney J -- Sellebjerg, Finn -- Selmaj, Krzysztof W -- Sexton, David -- Shen, Ling -- Simms-Acuna, Brigid -- Skidmore, Sheila -- Sleiman, Patrick M A -- Smestad, Cathrine -- Sorensen, Per Soelberg -- Sondergaard, Helle Bach -- Stankovich, Jim -- Strange, Richard C -- Sulonen, Anna-Maija -- Sundqvist, Emilie -- Syvanen, Ann-Christine -- Taddeo, Francesca -- Taylor, Bruce -- Blackwell, Jenefer M -- Tienari, Pentti -- Bramon, Elvira -- Tourbah, Ayman -- Brown, Matthew A -- Tronczynska, Ewa -- Casas, Juan P -- Tubridy, Niall -- Corvin, Aiden -- Vickery, Jane -- Jankowski, Janusz -- Villoslada, Pablo -- Markus, Hugh S -- Wang, Kai -- Mathew, Christopher G -- Wason, James -- Palmer, Colin N A -- Wichmann, H-Erich -- Plomin, Robert -- Willoughby, Ernest -- Rautanen, Anna -- Winkelmann, Juliane -- Wittig, Michael -- Trembath, Richard C -- Yaouanq, Jacqueline -- Viswanathan, Ananth C -- Zhang, Haitao -- Wood, Nicholas W -- Zuvich, Rebecca -- Deloukas, Panos -- Langford, Cordelia -- Duncanson, Audrey -- Oksenberg, Jorge R -- Pericak-Vance, Margaret A -- Haines, Jonathan L -- Olsson, Tomas -- Hillert, Jan -- Ivinson, Adrian J -- De Jager, Philip L -- Peltonen, Leena -- Stewart, Graeme J -- Hafler, David A -- Hauser, Stephen L -- McVean, Gil -- Donnelly, Peter -- Compston, Alastair -- 068545/Z/02/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084702/Wellcome Trust/United Kingdom -- 085475/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 898/Multiple Sclerosis Society/United Kingdom -- AI076544/AI/NIAID NIH HHS/ -- CA104021/CA/NCI NIH HHS/ -- G0100594/Medical Research Council/United Kingdom -- G0400017/Medical Research Council/United Kingdom -- G0700061/Medical Research Council/United Kingdom -- G0901310/Medical Research Council/United Kingdom -- G0901461/Medical Research Council/United Kingdom -- G19/2/Medical Research Council/United Kingdom -- K23N/S048869/PHS HHS/ -- NS032830/NS/NINDS NIH HHS/ -- NS049477/NS/NINDS NIH HHS/ -- NS049510/NS/NINDS NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS19142/NS/NINDS NIH HHS/ -- NS26799/NS/NINDS NIH HHS/ -- NS43559/NS/NINDS NIH HHS/ -- PDA/02/06/016/Department of Health/United Kingdom -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS049477/NS/NINDS NIH HHS/ -- R01 NS049477-06A1/NS/NINDS NIH HHS/ -- RR020092/RR/NCRR NIH HHS/ -- RR024992/RR/NCRR NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833088" target="_blank"〉PubMed〈/a〉

Description: Nutrients are supplied to the mixed layer of the open ocean by either atmospheric deposition or mixing from deeper waters, and these nutrients drive nitrogen and carbon fixation. To evaluate the importance of atmospheric deposition, we estimate marine nitrogen and carbon fixation from present-day simulations of atmospheric deposition of nitrogen, phosphorus, and iron. These are compared with observed rates of marine nitrogen and carbon fixation. We find that Fe deposition is more important than P deposition in supporting N fixation. Estimated rates of atmospherically supported carbon fixation are considerably lower than rates of marine carbon fixation derived from remote sensing, indicating the subsidiary role atmospheric deposition plays in total C uptake by the oceans. Nonetheless, in high-nutrient, low-chlorophyll areas, the contribution of atmospheric deposition of Fe to the surface ocean could account for about 50% of C fixation. In marine areas typically thought to be N limited, potential C fixation supported by atmospheric deposition of N is only ∼1%–2% of observed rates. Although these systems are N-limited, the amount of N supplied from below appears to be much larger than that deposited from above. Atmospheric deposition of Fe has the potential to augment atmospherically supported rates of C fixation in N-limited areas. In these areas, atmospheric Fe relieves the Fe limitation of diazotrophic organisms, thus contributing to the rate of N fixation. The most important uncertainties in understanding the relative importance of different atmospheric nutrients are poorly understood speciation and solubility of Fe as well as the N:Fe ratio of diazotrophic organisms.

Description: We review the human actions, proximal stressors and ecological responses for floodplain forests Australia's largest river system—the Murray-Darling Basin. A conceptual model for the floodplain forests was built from extensive published information and some unpublished results for the system, which should provide a basis for understanding, studying and managing the ecology of floodplains that face similar environmental stresses. Since European settlement, lowlands areas of the basin have been extensively cleared for agriculture and remnant forests heavily harvested for timber. The most significant human intervention is modification of river flows, and the reduction in frequency, duration and timing of flooding, which are compounded by climate change (higher temperatures and reduced rainfall) and deteriorating groundwater conditions (depth and salinity). This has created unfavorable conditions for all life-history stages of the dominant floodplain tree (Eucalyptus camaldulensis Dehnh.). Lack of extensive flooding has led to widespread dieback across the Murray River floodplain (currently 79% by area). Management for timber resources has altered the structure of these forests from one dominated by large, widely spreading trees to mixed-aged stands of smaller pole trees. Reductions in numbers of birds and other vertebrates followed the decline in habitat quality (hollow-bearing trees, fallen timber). Restoration of these forests is dependent on substantial increases in the frequency and extent of flooding, improvements in groundwater conditions, re-establishing a diversity of forest structures, removal of grazing and consideration of these interacting stressors.

Description: Climate variability affects the capacity of the biosphere to assimilate and store important elements, such as nitrogen and carbon. Here we present biogeochemical evidence from the sediments of tropical Lake Titicaca indicating that large hydrologic changes in response to global glacial cycles during the Quaternary were accompanied by major shifts in ecosystem state. During prolonged glacial intervals, lake level was high and the lake was in a stable nitrogen-limited state. In contrast, during warm dry interglacials lake level fell and rates of nitrogen concentrations increased by a factor of 4–12, resulting in a fivefold to 24-fold increase in organic carbon concentrations in the sediments due to increased primary productivity. Observed periods of increased primary productivity were also associated with an apparent increase in denitrification. However, the net accumulation of nitrogen during interglacial intervals indicates that increased nitrogen supply exceeded nitrogen losses due to denitrification, thereby causing increases in primary productivity. Although primary productivity in tropical ecosystems, especially freshwater ecosystems, tends to be nitrogen limited, our results indicate that climate variability may lead to changes in nitrogen availability and thus changes in primary productivity. Therefore some tropical ecosystems may shift between a stable state of nitrogen limitation and a stable state of nitrogen saturation in response to varying climatic conditions.

Description: It is increasingly clear that U.S. economic vitality and development, as well as global competitiveness, have strong and enduring ties to the space segment. Remote sensing, communications, surveillance, and a host of other areas of U.S. leadership are underpinned by space technology. Moreover, our national pursuit of robotic and human space exploration remains a cornerstone of U.S. aspirations. As was made clear in the U.S. National Space Policy (NSP) issued by President Barack Obama on 28 June 2010, a central overlay of the U.S. space program is that we must understand, be able to forecast, and, if possible, mitigate the effects of the space environment on technological systems.

Description: We have synthesized high-purity Yb 3+ -doped Lu 2 O 3 powder by the coprecipitation method. We have demonstrated that the recrystallization of the metal nitrates greatly improve the chemical purity of the resulting oxides. From thermogravimetry and differential thermal analysis study, we have calculated the approximate formula of the oxinitrate precipitate precursor as Lu 1.8 Yb 0.2 (OH) 5.44 (NO 3 ) 0.56 ·0.58H 2 O. Fine and soft agglomerate powders were obtained after calcinations. We have shown that the powder is mainly in the form of polycrystalline soft agglomerates composed with 15–20 nm size crystals. The resulting ceramic showed higher transparency (close to theoretical limit) compared with the ones fabricated with commercial powders.

Description: We identified 1875 wave events in magnetic field data from geosynchronous orbit. Most of these events were transverse with respect to the background magnetic field, left-hand polarized, and were observed in the post-noon magnetic local time sector at frequencies just below the helium gyrofrequency. Combined, these observations strongly suggest that most of these events are Electromagnetic Ion Cyclotron (EMIC) waves. Average wave amplitudes are presented, binned by frequency, geomagnetic activity and magnetic local time. The amplitude increases with increasing geomagnetic activity; increased activity also narrows the local time sector in which the waves are observed. A superposed epoch analysis of solar wind parameters and geomagnetic activity indices shows that 12 hours before wave onset the AE and Kp index increased, indicating storm and substorm activity that injects hot ion populations needed to drive the EMIC instability and providing ample time for those populations to drift into the post-noon local time sector. Just before wave onset a sudden enhancement in the AE index and the solar wind dynamic pressure are observed, indicating that a final perturbation of the magnetosphere is needed to excite EMIC wave growth. EMIC waves are thought to cause loss of relativistic particles in the radiation belt. Large solar wind densities have been associated with low flux of relativistic particles during the recovery phase of geomagnetic storms. We show that EMIC waves are preferentially generated during intervals of large solar wind density, indicating that such conditions drive EMIC waves which in turn cause enhanced loss of relativistic particles.

Description: A comparison of MeV electron measurements at geosynchronous orbit, GEO, with solar wind shows that the MeV electron prediction model developed for GEO using data from the declining phase of solar cycle 22 (1995–1996) works well for the declining phase of solar cycle 23 (2006–2008), indicating that the MeV electron flux has a predictable and systematic response to the solar wind. The same comparison for solar maximum (2000–2003) shows that the model works less well partly because it does not match the high flux cutoff seen in the data and partly because it does not reproduce the sudden drops in flux that occur when the magnetopause is close to GEO. The model also reproduces the nonlinear correlation of the solar wind speed with the log of the MeV electron flux seen at GEO. An examination of 15 yr of solar wind and the MeV electron data shows that geomagnetic activity driven by a southward orientation of the interplanetary magnetic field, IMF, is a necessary condition for MeV electron enhancements at GEO and that high-speed solar wind are not necessary. The reason that high-speed solar wind is almost always associated with the enhancement of MeV electrons is mainly because high-speed solar wind almost always has some southward components of the IMF.

Description: Numerical models of bedrock valley development generally do not include weathering explicitly. Nevertheless, weathering is an essential process that acts in concert with the transport of loose debris by seepage and runoff to form many bedrock valleys. Here we propose a numerical model for bedrock valley development that explicitly distinguishes weathering and the transport of loose debris and is capable of forming bedrock valleys similar to those observed in nature. In the model, weathering rates are assumed to increase with increasing water availability, a relationship that data suggest likely applies in many water-limited environments. We compare and contrast the model results for cases in which weathering is the result of runoff-induced infiltration versus cases in which it is the result of seepage- or subsurface-driven flow. The surface flow–driven version of our model represents an alternative to the stream-power model that explicitly shows how rates of both weathering and the transport of loose debris are related to topography or water flow. The subsurface flow–driven version of our model can be solved analytically using the linearized Boussinesq approximation. In such cases the model predicts theater-headed valleys that are parabolic in planform, a prediction broadly consistent with the observed shapes of theater-headed bedrock valleys on Mars that have been attributed to a combination of seepage weathering and episodic removal of weathered debris by runoff, seepage, and/or spring discharge.