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1.
  • Wang, Li-San, et al. (author)
  • Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
  • 2015
  • In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
  • Journal article (peer-reviewed)abstract
    • Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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2.
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3.
  • Roy, Sushmita, et al. (author)
  • Identification of functional elements and regulatory circuits by Drosophila modENCODE.
  • 2010
  • In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
  • Journal article (peer-reviewed)abstract
    • To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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4.
  • Van Deerlin, Vivian M, et al. (author)
  • Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
  • Journal article (peer-reviewed)abstract
    • Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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5.
  • Zody, Michael, 1968-, et al. (author)
  • DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage
  • 2006
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 440:7087, s. 1045-1049
  • Journal article (peer-reviewed)abstract
    • Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.
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6.
  • 2019
  • Journal article (peer-reviewed)
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7.
  • Abazajian, Kevork, et al. (author)
  • CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Journal article (peer-reviewed)abstract
    • CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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8.
  • Conradson, Steven D., et al. (author)
  • Closure of the Mott gap and formation of a superthermal metal in the Frohlich-type nonequilibrium polaron Bose-Einstein condensate in UO2+x
  • 2017
  • In: Physical Review B. - 2469-9950 .- 2469-9969. ; 96:12
  • Journal article (peer-reviewed)abstract
    • Mixed valence O-doped UO2+x. and photoexcited UO2 containing transitory U3+ and U5+ host a coherent polaronic quantum phase (CPQP) that exhibits the characteristics of a Frohlich-type, nonequilibrium, phononcoupled Bose-Einstein condensate whose stability and coherence are amplified by collective, anharmonic motions of atoms and charges. Complementary to the available, detailed, real space information from scattering and EXAFS, an outstanding question is the electronic structure. Mapping the Mott gap in UO2, U4O9, and U3O7 with O XAS and NIXS and UM5 RIXS shows that O doping raises the peak of the U5f states of the valence band by similar to 0.4 eV relative to a calculated value of 0.25 eV. However, it lowers the edge of the conduction band by 1.5 eV vs the calculated 0.6 eV, a difference much larger than the experimental error. This 1.9 eV reduction in the gap width constitutes most of the 2-2.2 eV gap measured by optical absorption. In addition, the XAS spectra show a tail that will intersect the occupied U5f states and give a continuous density-of-states that increases rapidly above its constricted intersection. Femtosecond-resolved photoemission measurements of UO2, coincident with the excitation pulse with 4.7 eV excitation, show the unoccupied U5f states of UO2 and no hot electrons. 3.1 eV excitation, however, complements the O-doping results by giving a continuous population of electrons for several eV above the Fermi level. The CPQP in photoexcited UO2 therefore fulfills the criteria for a nonequilibrium condensate. The electron distributions resulting from both excitations persist for 5-10 ps, indicating that they are the final state that therefore forms without passing through the initial continuous distribution of nonthermal electrons observed for other materials. Three exceptional findings are: (1) the direct formation of both of these long lived (> 3-10 ps) excited states without the short lived nonthermal intermediate; (2) the superthermal metallic state is as or more stable than typical photoinduced metallic phases; and (3) the absence of hot electrons accompanying the insulating UO2 excited state. This heterogeneous, nonequilibrium, Frohlich BEC stabilized by a Fano-Feshbach resonance therefore continues to exhibit unique properties.
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9.
  • Phillips, Helen R. P., et al. (author)
  • Global distribution of earthworm diversity
  • 2019
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 366:6464, s. 480-
  • Journal article (peer-reviewed)abstract
    • Soil organisms, including earthworms, are a key component of terrestrial ecosystems. However, little is known about their diversity, their distribution, and the threats affecting them. We compiled a global dataset of sampled earthworm communities from 6928 sites in 57 countries as a basis for predicting patterns in earthworm diversity, abundance, and biomass. We found that local species richness and abundance typically peaked at higher latitudes, displaying patterns opposite to those observed in aboveground organisms. However, high species dissimilarity across tropical locations may cause diversity across the entirety of the tropics to be higher than elsewhere. Climate variables were found to be more important in shaping earthworm communities than soil properties or habitat cover. These findings suggest that climate change may have serious implications for earthworm communities and for the functions they provide.
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10.
  • Weinstein, John N., et al. (author)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Research review (peer-reviewed)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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11.
  • Ade, Peter, et al. (author)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Journal article (peer-reviewed)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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12.
  • Anand, Shreya, et al. (author)
  • Collapsars as Sites of r-process Nucleosynthesis : Systematic Photometric Near-infrared Follow-up of Type Ic-BL Supernovae
  • 2024
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 962:1
  • Journal article (peer-reviewed)abstract
    • One of the open questions following the discovery of GW170817 is whether neutron star (NS) mergers are the only astrophysical sites capable of producing r-process elements. Simulations have shown that 0.01–0.1 M⊙ of r-process material could be generated in the outflows originating from the accretion disk surrounding the rapidly rotating black hole that forms as a remnant to both NS mergers and collapsing massive stars associated with long-duration gamma-ray bursts (collapsars). The hallmark signature of r-process nucleosynthesis in the binary NS merger GW170817 was its long-lasting near-infrared (NIR) emission, thus motivating a systematic photometric study of the light curves of broad-lined stripped-envelope (Ic-BL) supernovae (SNe) associated with collapsars. We present the first systematic study of 25 SNe Ic-BL—including 18 observed with the Zwicky Transient Facility and 7 from the literature—in the optical/NIR bands to determine what quantity of r-process material, if any, is synthesized in these explosions. Using semi-analytic models designed to account for r-process production in SNe Ic-BL, we perform light curve fitting to derive constraints on the r-process mass for these SNe. We also perform independent light curve fits to models without the r-process. We find that the r-process-free models are a better fit to the light curves of the objects in our sample. Thus, we find no compelling evidence of r-process enrichment in any of our objects. Further high-cadence infrared photometric studies and nebular spectroscopic analysis would be sensitive to smaller quantities of r-process ejecta mass or indicate whether all collapsars are completely devoid of r-process nucleosynthesis.
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13.
  • Beck, Bradley R.G., et al. (author)
  • Comparison of Constant PID Controller and Adaptive PID Controller via Reinforcement Learning for a Rehabilitation Robot
  • 2022
  • In: 2022 Australian &amp; New Zealand Control Conference (ANZCC). - : IEEE. - 9781665498876 ; , s. 218-223
  • Conference paper (peer-reviewed)abstract
    • Effectively tuning a PID controller can be difficult without prior experience or knowledge of the system being controlled. Reinforcement learning is a tool that allows automatic PID tuning with adaptability to environmental change. This technique was utilised for a single degree-of-freedom robot designed for human interaction, proving the validity of the TD3PG algorithm for reference tracking and rehabilitation exercises. These results were measured by the root mean square error of the system and compared to a classical PID controller to determine whether the adaptability improved the system tracking ability. Results showed the classical PID controller resulted in smaller RMSE measurements for a multitude of input signals including sine waves and multi-step functions when the environment remained constant. The adaptive PID controller resulted in smaller RMSE measurements for all input signals when the environment changed to reduce the amount of torque applied to the plant, representing a motor power failure. It is believed that a classic PID controller is better suited for systems with low input frequency and low system uncertainty while adaptive PID controllers are better for systems with changing environments or input signals.
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14.
  • Bellm, Eric C., et al. (author)
  • The Zwicky Transient Facility : System Overview, Performance, and First Results
  • 2019
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
  • Journal article (peer-reviewed)abstract
    • The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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15.
  • Blunden, Jessica, et al. (author)
  • State of the Climate in 2012
  • 2013
  • In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
  • Journal article (peer-reviewed)abstract
    • For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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16.
  • Blunden, Jessica, et al. (author)
  • State of the climate in 2013
  • 2014
  • In: Bulletin of the American Meteorological Society. - 0003-0007. ; 95
  • Journal article (peer-reviewed)abstract
    • © 2014, American Meteorological Society. All rights reserved. In 2013, the vast majority of the monitored climate variables reported here maintained trends established in recent decades. ENSO was in a neutral state during the entire year, remaining mostly on the cool side of neutral with modest impacts on regional weather patterns around the world. This follows several years dominated by the effects of either La Niña or El Niño events. According to several independent analyses, 2013 was again among the 10 warmest years on record at the global scale, both at the Earth’s surface and through the troposphere. Some regions in the Southern Hemisphere had record or near-record high temperatures for the year. Australia observed its hottest year on record, while Argentina and New Zealand reported their second and third hottest years, respectively. In Antarctica, Amundsen-Scott South Pole Station reported its highest annual temperature since records began in 1957. At the opposite pole, the Arctic observed its seventh warmest year since records began in the early 20th century. At 20-m depth, record high temperatures were measured at some permafrost stations on the North Slope of Alaska and in the Brooks Range. In the Northern Hemisphere extratropics, anomalous meridional atmospheric circulation occurred throughout much of the year, leading to marked regional extremes of both temperature and precipitation. Cold temperature anomalies during winter across Eurasia were followed by warm spring temperature anomalies, which were linked to a new record low Eurasian snow cover extent in May. Minimum sea ice extent in the Arctic was the sixth lowest since satellite observations began in 1979. Including 2013, all seven lowest extents on record have occurred in the past seven years. Antarctica, on the other hand, had above-average sea ice extent throughout 2013, with 116 days of new daily high extent records, including a new daily maximum sea ice area of 19.57 million km2 reached on 1 October. ENSO-neutral conditions in the eastern central Pacific Ocean and a negative Pacific decadal oscillation pattern in the North Pacific had the largest impacts on the global sea surface temperature in 2013. The North Pacific reached a historic high temperature in 2013 and on balance the globally-averaged sea surface temperature was among the 10 highest on record. Overall, the salt content in nearsurface ocean waters increased while in intermediate waters it decreased. Global mean sea level continued to rise during 2013, on pace with a trend of 3.2 mm yr-1 over the past two decades. A portion of this trend (0.5 mm yr-1) has been attributed to natural variability associated with the Pacific decadal oscillation as well as to ongoing contributions from the melting of glaciers and ice sheets and ocean warming. Global tropical cyclone frequency during 2013 was slightly above average with a total of 94 storms, although the North Atlantic Basin had its quietest hurricane season since 1994. In the Western North Pacific Basin, Super Typhoon Haiyan, the deadliest tropical cyclone of 2013, had 1-minute sustained winds estimated to be 170 kt (87.5 m s-1) on 7 November, the highest wind speed ever assigned to a tropical cyclone. High storm surge was also associated with Haiyan as it made landfall over the central Philippines, an area where sea level is currently at historic highs, increasing by 200 mm since 1970. In the atmosphere, carbon dioxide, methane, and nitrous oxide all continued to increase in 2013. As in previous years, each of these major greenhouse gases once again reached historic high concentrations. In the Arctic, carbon dioxide and methane increased at the same rate as the global increase. These increases are likely due to export from lower latitudes rather than a consequence of increases in Arctic sources, such as thawing permafrost. At Mauna Loa, Hawaii, for the first time since measurements began in 1958, the daily average mixing ratio of carbon dioxide exceeded 400 ppm on 9 May. The state of these variables, along with dozens of others, and the 2013 climate conditions of regions around the world are discussed in further detail in this 24th edition of the State of the Climate series.
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17.
  • Botvinik-Nezer, Rotem, et al. (author)
  • Variability in the analysis of a single neuroimaging dataset by many teams
  • 2020
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
  • Journal article (peer-reviewed)abstract
    • Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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18.
  • Bradley, Jonathan P., et al. (author)
  • Probing intermolecular crystal packing in gamma-indomethacin by high-resolution 1H solid-state NMR spectroscopy
  • 2011
  • In: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 11:8, s. 3463-3471
  • Journal article (peer-reviewed)abstract
    • An NMR crystallography approach that combines experimental solid-state magic-angle-spinning (MAS) NMR with calculation is applied to the gamma polymorph of the pharmaceutical molecule, indomethacin. First-principles calculations (GIPAW) for the full crystal structure and an isolated molecule show changes in the (1)H chemical shift for specific aliphatic and aromatic protons of over -1 ppm that are due to intermolecular CH-pi interactions. For the OH proton, (1)H double-quantum (DQ) CRAMPS (combined rotation and multiple-pulse spectroscopy) spectra reveal intermolecular H-H proximities to the OH proton of the carboxylic acid dimer as well as to specific aromatic CH protons. The enhanced resolution in (1)H DQ-(13)C spectra, recorded at 850 MHz, enables separate (1)H DQ build-up curves (as a function of the DQ recoupling time) to be extracted for the aromatic CH protons. Supported by eight-spin density-matrix simulations, it is shown how the relative maximum intensities and rates of build-up provide quantitative insight into intramolecular and intermolecular H-H proximities that characterize the crystal packing
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19.
  • Bradley, Steven, et al. (author)
  • A Methodology for Investigating Women's Module Choices in Computer Science
  • 2023
  • In: ITiCSE 2023. - : Association for Computing Machinery (ACM). - 9798400701399 ; , s. 569-570
  • Conference paper (peer-reviewed)abstract
    • At ITiCSE 2021, Working Group 3 examined the evidence for teaching practices that broaden participation for women in computing, based on the National Center for Women & Information Technology (NCWIT) Engagement Practices framework. One of the report's recommendations was "Make connections from computing to your students' lives and interests (Make it Matter) but don't assume you know what those interests are; find out!" The goal of this 2023 working group is to find out what interests women students by bringing together data from our institutions on undergraduate module enrollment, seeing how they differ for women and men, and what drives those choices. We will code published module content based on ACM curriculum guidelines and combine these data to build a hierarchical statistical model of factors affecting student choice. This model should be able to tell us how interesting or valuable different topics are to women, and to what extent topic affects choice of module - as opposed to other factors such as the instructor, the timetable, or the mode of assessment. Equipped with this knowledge we can advise departments how to focus curriculum development on areas that are of value to women, and hence work towards making the discipline more inclusive.
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20.
  • Bradley, Steven, et al. (author)
  • Modeling Women's Elective Choices in Computing
  • 2023
  • In: ITiCSE-WGR '23. - : Association for Computing Machinery (ACM). - 9798400704055 ; , s. 196-226
  • Conference paper (peer-reviewed)abstract
    • Evidence-based strategies suggest ways to reduce the gender gap in computing. For example, elective classes are valuable in enabling students to choose in which directions to expand their computing knowledge in areas aligned with their interests. The availability of electives of interest may also make computing programs of study more meaningful to women. However, research on which elective computing topics are more appealing to women is often class or institution specific. In this study, we investigate differences in enrollment within undergraduate-level elective classes in computing to study differences between women and men. The study combined data from nine institutions from both Western Europe and North America and included 272 different classes with 49,710 student enrollments. These classes were encoded using ACM curriculum guidelines and combined with the enrollment data to build a hierarchical statistical model of factors affecting student choice. Our model shows which elective topics are less popular with all students (including fundamentals of programming languages and parallel and distributed computing), and which elective topics are more popular with women students (including mathematical and statistical foundations, human computer interaction and society, ethics, and professionalism). Understanding which classes appeal to different students can help departments gain insight of student choices and develop programs accordingly. Additionally, these choices can also help departments explore whether some students are less likely to choose certain classes than others, indicating potential barriers to participation in computing.
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21.
  • Bradley, Steven W., et al. (author)
  • Policy for innovative entrepreneurship: Institutions, interventions, and societal challenges
  • 2021
  • In: Strategic Entrepreneurship Journal. - : WILEY. - 1932-4391 .- 1932-443X. ; 15:2, s. 167-184
  • Journal article (peer-reviewed)abstract
    • Research Summary Innovative entrepreneurship, defined as the creation of new products, services, production methods, or business models, is critical for firm, industry, and economic growth and a key determinant of societal well-being. This special issue explores the roles of institutions and government policies in promoting or impeding innovative entrepreneurship. In this introductory editorial, we review theory and evidence on entrepreneurship at the macro-institutional and micro-policy levels, highlighting costs and benefits of alternative institutional environments and targeted policy interventions, as well as interactions within and across levels. We summarize the six papers in the special issue, discuss their contributions to the literature, and suggest how future work can build upon these and other papers to advance our understanding of the conditions and mechanisms underlying successful entrepreneurial innovation. Managerial Summary Innovation and entrepreneurship bring new products and services to market, help firms and industries to grow, and generate improvements in social and economic life. The papers in this special issue explore the background conditions-laws, political processes, regulations, tax policy, subsidies, training programs, and more-that make entrepreneurship and innovation successful. Both "macro" and "micro" policies can stimulate successful entrepreneurial and innovative outcomes, but can also become politicized, be ineffective, and generate unintended consequences. The papers offer lessons to researchers, policymakers, and practitioners about making entrepreneurship and innovation more successful.
  •  
22.
  • Bradley, Steven W., et al. (author)
  • Resources, environmental change, and survival : Asymmetric paths of young independent and subsidiary organizations
  • 2011
  • In: Strategic Management Journal. - : John Wiley & Sons. - 0143-2095 .- 1097-0266. ; 32:5, s. 486-509
  • Journal article (peer-reviewed)abstract
    • Using an evolutionary model and a sample of 7,166 firms in the manufacturing and technology sectors of Sweden, we find that surviving organizations founded independent of a parent organization have lower long-term failure rates than their protected subsidiary counterparts. Specifically, we find that subsidiary organizations have low mortality rates when compared to independent organizations, but that their mortality rates increase more rapidly during a severe economic downturn. We also find evidence that surviving independent organizations are more capable than subsidiary organizations of using their resources to reduce mortality rates during an environmental jolt. Overall, our findings strengthen the notion that organizational adaptation is linked not only to ecological and strategic processes but also to organizational structure.
  •  
23.
  • Bradley, Steven W., et al. (author)
  • Swinging a double-edged sword : The effect of slack on entrepreneurial management and growth
  • 2011
  • In: Journal of Business Venturing. - : Elsevier. - 0883-9026 .- 1873-2003. ; 26:5, s. 537-554
  • Journal article (peer-reviewed)abstract
    • Resource slack represents a double-edged sword, simultaneously fueling and hindering growth. Drawing on Penrose's growth theory and Stevenson's entrepreneurial management theory, we have developed and tested a conceptual model that provides a more nuanced account of the resource slack–growth relationship. Using a large dataset spanning six years, we have found that slack has a positive direct effect on growth but a negative effect on entrepreneurial management, and that entrepreneurial management has a positive effect on growth. Our empirical and conceptual findings are important to the development of firm growth theory and explicate causal mechanisms transforming slack into firm-level outcomes.
  •  
24.
  • Bradley, Steven W., et al. (author)
  • The importance of slack for new organizations facing 'tough' environments
  • 2011
  • In: Journal of Management Studies. - : John Wiley & Sons. - 0022-2380 .- 1467-6486. ; 48:5, s. 1071-1097
  • Journal article (peer-reviewed)abstract
    • Strategy-based models centre on the management of unique and valuable resources to take advantage of specific market opportunities. Less examined in this approach are the roles of slack resources in the process of generating firm value – particularly for new firms in ‘tough’ environments where fewer opportunities are available. Using a cohort panel of 951 new manufacturing firms over nine years, our findings provide evidence for the importance of financial slack resources in understanding opportunity generation and also for reconciling theoretical arguments regarding the slack resource–performance link. We find that while financial slack does provide buffering capacity (in hostile and dynamic environments), and flexibility for experimentation (in munificent and dynamic environments) as suggested by prior theory, the most positive relationship between financial slack and performance for new firms was in low discretion environments (hostile and stable environments) – where firms need to develop their own opportunities. The implications of these findings for theory are discussed.
  •  
25.
  • Clark, Andrew G., et al. (author)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Journal article (peer-reviewed)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
  •  
26.
  • Crary, John F., et al. (author)
  • Primary age-related tauopathy (PART) : a common pathology associated with human aging
  • 2014
  • In: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 128:6, s. 755-766
  • Journal article (peer-reviewed)abstract
    • We recommend a new term, "primary age-related tauopathy" (PART), to describe a pathology that is commonly observed in the brains of aged individuals. Many autopsy studies have reported brains with neurofibrillary tangles (NFTs) that are indistinguishable from those of Alzheimer's disease (AD), in the absence of amyloid (A beta) plaques. For these "NFT+/A beta-aEuroe brains, for which formal criteria for AD neuropathologic changes are not met, the NFTs are mostly restricted to structures in the medial temporal lobe, basal forebrain, brainstem, and olfactory areas (bulb and cortex). Symptoms in persons with PART usually range from normal to amnestic cognitive changes, with only a minority exhibiting profound impairment. Because cognitive impairment is often mild, existing clinicopathologic designations, such as "tangle-only dementia" and "tangle-predominant senile dementia", are imprecise and not appropriate for most subjects. PART is almost universally detectable at autopsy among elderly individuals, yet this pathological process cannot be specifically identified pre-mortem at the present time. Improved biomarkers and tau imaging may enable diagnosis of PART in clinical settings in the future. Indeed, recent studies have identified a common biomarker profile consisting of temporal lobe atrophy and tauopathy without evidence of A beta accumulation. For both researchers and clinicians, a revised nomenclature will raise awareness of this extremely common pathologic change while providing a conceptual foundation for future studies. Prior reports that have elucidated features of the pathologic entity we refer to as PART are discussed, and working neuropathological diagnostic criteria are proposed.
  •  
27.
  • de Gonzalez, Amy Berrington, et al. (author)
  • Body-Mass Index and Mortality among 1.46 Million White Adults.
  • 2010
  • In: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 363:23, s. 2211-2219
  • Journal article (peer-reviewed)abstract
    • Background: A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain. Methods: We used Cox regression to estimate hazard ratios and 95% confidence intervals for an association between BMI and all-cause mortality, adjusting for age, study, physical activity, alcohol consumption, education, and marital status in pooled data from 19 prospective studies encompassing 1.46 million white adults, 19 to 84 years of age (median, 58). Results: The median baseline BMI was 26.2. During a median follow-up period of 10 years (range, 5 to 28), 160,087 deaths were identified. Among healthy participants who never smoked, there was a J-shaped relationship between BMI and all-cause mortality. With a BMI of 22.5 to 24.9 as the reference category, hazard ratios among women were 1.47 (95 percent confidence interval [CI], 1.33 to 1.62) for a BMI of 15.0 to 18.4; 1.14 (95% CI, 1.07 to 1.22) for a BMI of 18.5 to 19.9; 1.00 (95% CI, 0.96 to 1.04) for a BMI of 20.0 to 22.4; 1.13 (95% CI, 1.09 to 1.17) for a BMI of 25.0 to 29.9; 1.44 (95% CI, 1.38 to 1.50) for a BMI of 30.0 to 34.9; 1.88 (95% CI, 1.77 to 2.00) for a BMI of 35.0 to 39.9; and 2.51 (95% CI, 2.30 to 2.73) for a BMI of 40.0 to 49.9. In general, the hazard ratios for the men were similar. Hazard ratios for a BMI below 20.0 were attenuated with longer-term follow-up. Conclusions: In white adults, overweight and obesity (and possibly underweight) are associated with increased all-cause mortality. All-cause mortality is generally lowest with a BMI of 20.0 to 24.9. N Engl J Med 2010;363:2211-9.
  •  
28.
  • Ding, Li, et al. (author)
  • Somatic mutations affect key pathways in lung adenocarcinoma
  • 2008
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
  • Journal article (peer-reviewed)abstract
    • Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
  •  
29.
  • Doumpas, Nikolaos, et al. (author)
  • TCF/LEF regulation of the topologically associated domain ADI promotes mESCs to exit the pluripotent ground state
  • 2021
  • In: Cell Reports. - : Cell Press. - 2211-1247. ; 36:11
  • Journal article (peer-reviewed)abstract
    • Mouse embryonic stem cells (mESCs) can bemaintained in vitro in defined N2B27 medium supplemented with two chemical inhibitors for GSK3 and MEK (2i) and the cytokine leukemia inhibitory factor (LIF), which act synergistically to promote self-renewal and pluripotency. Here, we find that genetic deletion of the four genes encoding the TCF/LEF transcription factors confersm ESCs with the ability to self-renew in N2B27 medium alone. TCF/LEF quadruple knockout (qKO) mESCs display dysregulation of several genes, including Aire, Dnmt3l, and IcosL, located adjacent to each other within a topologically associated domain (TAD). Aire, Dnmt3l, and IcosL appear to be regulated by TCF/LEF in a beta-catenin independent manner. Moreover, downregulation of Aire and Dnmt3l in wild-type mESCs mimics the loss of TCF/LEF and increases mESC survival in the absence of 2iL. Hence, this study identifies TCF/LEF effectors that mediate exit from the pluripotent state.
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30.
  • Elsik, Christine G., et al. (author)
  • The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
  • 2009
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
  • Journal article (peer-reviewed)abstract
    • To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
  •  
31.
  • Foerster, Bradley R., et al. (author)
  • Reduced insular gamma-aminobutyric acid in fibromyalgia
  • 2012
  • In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:2, s. 579-583
  • Journal article (peer-reviewed)abstract
    • Objective Recent scientific findings have reinvigorated interest in examining the role of gamma-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressurepain thresholds. Methods. Sixteen FM patients and 17 age-and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. Results. GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean +/- SD 1.17 +/- 0.24 arbitrary institutional units versus 1.42 +/- 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressurepain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). Conclusion. Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.
  •  
32.
  • Fogh, Isabella, et al. (author)
  • Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis
  • 2016
  • In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 73:7, s. 812-820
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. OBJECTIVE To identify gene variants influencing survival in ALS. DESIGN, SETTING, AND PARTICIPANTS This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. MAIN OUTCOMES AND MEASURES Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed bymeta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. RESULTS Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 x 10(-9)) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 x 10(-8)). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 x 10(-9)), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 x 10(-8)), corresponding to a 4-month reduction in survival compared with TT carriers. CONCLUSIONS AND RELEVANCE This GWAS robustly identified 2 loci at genome-wide levels of significance that influence survival in patients with ALS. Because ALS is a rare disease and prevention is not feasible, treatment that modifies survival is the most realistic strategy. Therefore, identification of modifier genes that might influence ALS survival could improve the understanding of the biology of the disease and suggest biological targets for pharmaceutical intervention. In addition, genetic risk scores for survival could be used as an adjunct to clinical trials to account for the genetic contribution to survival.
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33.
  • Foote, Andrew D., et al. (author)
  • Killer whale genomes reveal a complex history of recurrent admixture and vicariance
  • 2019
  • In: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 28:14, s. 3427-3444
  • Journal article (peer-reviewed)abstract
    • Reconstruction of the demographic and evolutionary history of populations assuming a consensus tree-like relationship can mask more complex scenarios, which are prevalent in nature. An emerging genomic toolset, which has been most comprehensively harnessed in the reconstruction of human evolutionary history, enables molecular ecologists to elucidate complex population histories. Killer whales have limited extrinsic barriers to dispersal and have radiated globally, and are therefore a good candidate model for the application of such tools. Here, we analyse a global data set of killer whale genomes in a rare attempt to elucidate global population structure in a nonhuman species. We identify a pattern of genetic homogenisation at lower latitudes and the greatest differentiation at high latitudes, even between currently sympatric lineages. The processes underlying the major axis of structure include high drift at the edge of species' range, likely associated with founder effects and allelic surfing during postglacial range expansion. Divergence between Antarctic and non-Antarctic lineages is further driven by ancestry segments with up to fourfold older coalescence time than the genome-wide average; relicts of a previous vicariance during an earlier glacial cycle. Our study further underpins that episodic gene flow is ubiquitous in natural populations, and can occur across great distances and after substantial periods of isolation between populations. Thus, understanding the evolutionary history of a species requires comprehensive geographic sampling and genome-wide data to sample the variation in ancestry within individuals.
  •  
34.
  • Hammerstein, Erica, et al. (author)
  • The Final Season Reimagined : 30 Tidal Disruption Events from the ZTF-I Survey
  • 2023
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 942:1
  • Journal article (peer-reviewed)abstract
    • Tidal disruption events (TDEs) offer a unique way to study dormant black holes. While the number of observed TDEs has grown thanks to the emergence of wide-field surveys in the past few decades, questions regarding the nature of the observed optical, UV, and X-ray emission remain. We present a uniformly selected sample of 30 spectroscopically classified TDEs from the Zwicky Transient Facility Phase I survey operations with follow-up Swift UV and X-ray observations. Through our investigation into correlations between light-curve properties, we recover a shallow positive correlation between the peak bolometric luminosity and decay timescales. We introduce a new spectroscopic class of TDE, TDE-featureless, which are characterized by featureless optical spectra. The new TDE-featureless class shows larger peak bolometric luminosities, peak blackbody temperatures, and peak blackbody radii. We examine the differences between the X-ray bright and X-ray faint populations of TDEs in this sample, finding that X-ray bright TDEs show higher peak blackbody luminosities than the X-ray faint subsample. This sample of optically selected TDEs is the largest sample of TDEs from a single survey yet, and the systematic discovery, classification, and follow-up of this sample allows for robust characterization of TDE properties, an important stepping stone looking forward toward the Rubin era.
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35.
  • Hsiao, Tiger Yu-Yang, et al. (author)
  • JWST Reveals a Possible z similar to 11 Galaxy Merger in Triply Lensed MACS0647-JD
  • 2023
  • In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 949:2
  • Journal article (peer-reviewed)abstract
    • MACS0647-JD is a triply lensed z similar to 11 galaxy originally discovered with the Hubble Space Telescope. The three lensed images are magnified by factors of similar to 8, 5, and 2 to AB mag 25.1, 25.6, and 26.6 at 3.5 mu m. The brightest is over a magnitude brighter than other galaxies recently discovered at similar redshifts z > 10 with JWST. Here, we report new JWST imaging that clearly resolves MACS0647-JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. The brighter larger component "A" is intrinsically very blue (ss similar to-2.6 +/- 0.1), likely due to very recent star formation and no dust, and is spatially extended with an effective radius similar to 70 +/- 24 pc. The smaller component "B" (r similar to 20-+ 58 pc) appears redder (ss similar to-2 +/- 0.2), likely because it is older (100-200 Myr) with mild dust extinction (AV similar to 0.1 mag). With an estimated stellar mass ratio of roughly 2:1 and physical projected separation similar to 400 pc, we may be witnessing a galaxy merger 430 million years after the Big Bang. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be dissimilar, which is also suggested by the spectral energy distribution fitting, suggesting they formed further apart. We also identify a candidate companion galaxy "C" similar to 3 kpc away, likely destined to merge with A and B. Upcoming JWST Near Infrared Spectrograph observations planned for 2023 January will deliver spectroscopic redshifts and more physical properties for these tiny magnified distant galaxies observed in the early universe.
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36.
  •  
37.
  • Jones, Gregory T., et al. (author)
  • Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
  • 2017
  • In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
  • Journal article (peer-reviewed)abstract
    • Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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38.
  • Kattge, Jens, et al. (author)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Journal article (peer-reviewed)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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39.
  • Lewin, Harris A., et al. (author)
  • The Earth BioGenome Project 2020 : Starting the clock
  • 2022
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
  • Journal article (other academic/artistic)
  •  
40.
  • Linton, Steven J., 1952-, et al. (author)
  • The secondary prevention of low back pain : a controlled study with follow-up
  • 1989
  • In: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 36:2, s. 197-207
  • Journal article (peer-reviewed)abstract
    • The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting-list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow-up. In addition, the treatment group broke a trend for increasing amounts of pain-related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.
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41.
  • McDevitt, Michael R., et al. (author)
  • Feed-forward alpha particle radiotherapy ablates androgen receptor-addicted prostate cancer
  • 2018
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Human kallikrein peptidase 2 (hK2) is a prostate specific enzyme whose expression is governed by the androgen receptor (AR). AR is the central oncogenic driver of prostate cancer (PCa) and is also a key regulator of DNA repair in cancer. We report an innovative therapeutic strategy that exploits the hormone-DNA repair circuit to enable molecularly-specific alpha particle irradiation of PCa. Alpha-particle irradiation of PCa is prompted by molecularly specific-targeting and internalization of the humanized monoclonal antibody hu11B6 targeting hK2 and further accelerated by inherent DNA-repair that up-regulate hK2 (KLK2) expression in vivo. hu11B6 demonstrates exquisite targeting specificity for KLK2. A single administration of actinium-225 labeled hu11B6 eradicates disease and significantly prolongs survival in animal models. DNA damage arising from alpha particle irradiation induces AR and subsequently KLK2, generating a unique feed-forward mechanism, which increases binding of hu11B6. Imaging data in nonhuman primates support the possibility of utilizing hu11B6 in man.
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42.
  • Mondal, Rajesh, et al. (author)
  • The multifrequency angular power spectrum in parameter studies of the cosmic 21-cm signal
  • 2022
  • In: Monthly Notices of the Royal Astronomical Society: Letters. - : Oxford University Press (OUP). - 1745-3925 .- 1745-3933. ; 514:1, s. L31-L35
  • Journal article (peer-reviewed)abstract
    • The light-cone effect breaks the periodicity and statistical homogeneity (ergodicity) along the line-of-sight direction of cosmological emission/absorption line surveys. The spherically averaged power spectrum (SAPS), which by definition assumes ergodicity and periodicity in all directions, can only quantify some of the second-order statistical information in the 3D light-cone signals, and therefore, gives a biased estimate of the true statistics. The multifrequency angular power spectrum (MAPS), by extracting more information from the data, does not rely on these assumptions. It is therefore better aligned with the properties of the signal. We have compared the performance of the MAPS and SAPS metrics for parameter estimation of a mock 3D light-cone observation of the 21-cm signal from the Epoch of Reionization. Our investigation is based on a simplified 3-parameter 21cmFAST model. We find that the MAPS produces parameter constraints, which are a factor of ∼2 more stringent than when the SAPS is used. The significance of this result does not change much even in the presence of instrumental noise expected for 128 h of SKA-Low observations. Our results therefore suggest that a parameter estimation framework based on the MAPS metric would yield superior results over one using the SAPS metric. 
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43.
  • Nicolas, Aude, et al. (author)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • In: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Journal article (peer-reviewed)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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44.
  •  
45.
  • Trott, Cathryn M., et al. (author)
  • Multi-frequency angular power spectrum of the 21 cm signal from the Epoch of Reionisation using the Murchison Widefield Array
  • 2022
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Journal article (peer-reviewed)abstract
    • Context. The Multi-frequency Angular Power Spectrum (MAPS) is an alternative to spherically averaged power spectra, and computes local fluctuations in the angular power spectrum without need for line-of-sight spectral transform.Aims. We aimed to test different approaches to MAPS and treatment of the foreground contamination, and compare with the spherically averaged power spectrum, and the single-frequency angular power spectrum.Methods. We applied the MAPS to 110 h of data in z = 6.2 − 7.5 obtained for the Murchison Widefield Array Epoch of Reionisation experiment to compute the statistical power of 21 cm brightness temperature fluctuations. In the presence of bright foregrounds, a filter was applied to remove large-scale modes prior to MAPS application, significantly reducing MAPS power due to systematics.Results. The MAPS showed a contrast of 102–103 to a simulated 21 cm cosmological signal for spectral separations of 0−4 MHz after application of the filter, reflecting results for the spherically averaged power spectrum. The single-frequency angular power spectrum was also computed. At z = 7.5 and l = 200, we found an angular power of 53 mK2, exceeding a simulated cosmological signal power by a factor of one thousand. Residual spectral structure, inherent to the calibrated data, and not spectral leakage from large-scale modes, was the dominant source of systematic power bias. The single-frequency angular power spectrum yielded slightly poorer results compared with the spherically averaged power spectrum, having applied a spectral filter to reduce foregrounds. Exploration of other filters may improve this result, along with consideration of wider bandwidths.
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46.
  • Windhorst, Rogier A., et al. (author)
  • JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results
  • 2023
  • In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1
  • Journal article (peer-reviewed)abstract
    • We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
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47.
  • Witjes, J. Alfred, et al. (author)
  • EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer – An International Collaborative Multistakeholder Effort : Under the Auspices of the EAU-ESMO Guidelines Committees
  • 2020
  • In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 77:2, s. 223-250
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.
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48.
  • Wray, Selina, et al. (author)
  • Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research
  • 2012
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8
  • Journal article (peer-reviewed)abstract
    • Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community.
  •  
49.
  • Yao, Yuhan, et al. (author)
  • Tidal Disruption Event Demographics with the Zwicky Transient Facility : Volumetric Rates, Luminosity Function, and Implications for the Local Black Hole Mass Function
  • 2023
  • In: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 955:1
  • Journal article (peer-reviewed)abstract
    • We conduct a systematic tidal disruption event (TDE) demographics analysis using the largest sample of optically selected TDEs. A flux-limited, spectroscopically complete sample of 33 TDEs is constructed using the Zwicky Transient Facility over 3 yr (from 2018 October to 2021 September). We infer the black hole (BH) mass (MBH) with host galaxy scaling relations, showing that the sample MBH ranges from 105.1M⊙ to 108.2M⊙. We developed a survey efficiency corrected maximum volume method to infer the rates. The rest-frame g-band luminosity function can be well described by a broken power law of , with Lbk = 1043.1 erg s−1. In the BH mass regime of 105.3 ≲ (MBH/M⊙) ≲ 107.3, the TDE mass function follows , which favors a flat local BH mass function (). We confirm the significant rate suppression at the high-mass end (MBH ≳ 107.5M⊙), which is consistent with theoretical predictions considering direct capture of hydrogen-burning stars by the event horizon. At a host galaxy mass of Mgal ∼ 1010M⊙, the average optical TDE rate is ≈3.2 × 10−5 galaxy−1 yr−1. We constrain the optical TDE rate to be [3.7, 7.4, and 1.6] × 10−5 galaxy−1 yr−1 in galaxies with red, green, and blue colors.
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