| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)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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| 7. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 8. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 9. |
- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Allanach, Benjamin C., et al.
(författare)
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Simple and statistically sound strategies for analysing physical theories
- 2022
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Ingår i: Reports on progress in physics (Print). - : Institute of Physics Publishing (IOPP). - 0034-4885 .- 1361-6633. ; 85:5
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Forskningsöversikt (refereegranskat)abstract
- Physical theories that depend on many parameters or are tested against data from many different experiments pose unique challenges to statistical inference. Many models in particle physics, astrophysics and cosmology fall into one or both of these categories. These issues are often sidestepped with statistically unsound ad hoc methods, involving intersection of parameter intervals estimated by multiple experiments, and random or grid sampling of model parameters. Whilst these methods are easy to apply, they exhibit pathologies even in low-dimensional parameter spaces, and quickly become problematic to use and interpret in higher dimensions. In this article we give clear guidance for going beyond these procedures, suggesting where possible simple methods for performing statistically sound inference, and recommendations of readily-available software tools and standards that can assist in doing so. Our aim is to provide any physicists lacking comprehensive statistical training with recommendations for reaching correct scientific conclusions, with only a modest increase in analysis burden. Our examples can be reproduced with the code publicly available at Zenodo.
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| 11. |
- Baturova, Maria A., et al.
(författare)
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Electrocardiographic and Echocardiographic predictors of paroxysmal atrial fibrillation detected after ischemic stroke
- 2016
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Detection of atrial fibrillation after ischemic stroke is challenging due to its paroxysmal nature. We aimed to assess predictors of paroxysmal atrial fibrillation using non-invasive surface ECG and transthoracic echocardiography to select candidates for atrial fibrillation screening. Methods: Ischemic stroke patients without documented atrial fibrillation (n = 110, 67 ± 10 years, 40 female) and a control group of age- and gender-matched patients with history of paroxysmal atrial fibrillation prior to stroke (n = 55, 67 ± 10 years, 19 female) comprised the study sample. Using non-invasive ECG monitoring for three weeks, short episodes of paroxysmal atrial fibrillation were detected in 24 of 110 patients (22 %). The standard 12-lead ECG with sinus rhythm at stroke onset was digitally processed and analyzed. Transthoracic echocardiography data were reviewed for these patients. Results: Atrial fibrillation history was independently associated with P terminal force in lead V 1 > 40 mm*ms (OR 4.04 95 % CI 1.34-12.14, p = 0.013) and left atrial volume index (OR 1.08 95 % CI 1.03-1.13, p = 0.002; for LAVI > 40 mL/m2 OR 6.40 95 % CL 1.47-27.91, p = 0.013). Among patients without atrial fibrillation history, no ECG characteristics were predictive of atrial fibrillation detected after stroke. Left atrial volume index remained an independent predictor of atrial fibrillation detected after stroke (OR 1.09 95 % CI 1.02-1.16, p = 0.017). A cutoff of <40 mL/m2 had an 84 % negative predictive value for ruling out atrial fibrillation on ambulatory monitoring with a sensitivity of 50 % and a specificity of 86 %. Conclusion: In a post hoc analysis, left atrial dilatation assessed by left atrial volume index independently predicted atrial fibrillation after stroke in patients without prior atrial fibrillation history, while the other clinical or ECG markers were not predictive of atrial fibrillation detected early after ischemic stroke. Trial registration: This study is a post hoc analysis from the prospective case-control study registered in December 2011, ClinicalTrials.gov ID: NCT01325545.
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| 12. |
- Heuser, Michael, et al.
(författare)
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Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex.
- 2011
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Ingår i: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 20:1, s. 39-52
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Tidskriftsartikel (refereegranskat)abstract
- Pathways defining susceptibility of normal cells to oncogenic transformation may be valuable therapeutic targets. We characterized the cell of origin and its critical pathways in MN1-induced leukemias. Common myeloid (CMP) but not granulocyte-macrophage progenitors (GMP) could be transformed by MN1. Complementation studies of CMP-signature genes in GMPs demonstrated that MN1-leukemogenicity required the MEIS1/AbdB-like HOX-protein complex. ChIP-sequencing identified common target genes of MN1 and MEIS1 and demonstrated identical binding sites for a large proportion of their chromatin targets. Transcriptional repression of MEIS1 targets in established MN1 leukemias demonstrated antileukemic activity. As MN1 relies on but cannot activate expression of MEIS1/AbdB-like HOX proteins, transcriptional activity of these genes determines cellular susceptibility to MN1-induced transformation and may represent a promising therapeutic target.
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| 13. |
- Hosseinzadeh, Griffin, et al.
(författare)
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Weak Mass Loss from the Red Supergiant Progenitor of the Type II SN 2021yja
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 935:1
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Tidskriftsartikel (refereegranskat)abstract
- We present high-cadence optical, ultraviolet (UV), and near-infrared data of the nearby (D approximate to 23 Mpc) Type II supernova (SN) 2021yja. Many Type II SNe show signs of interaction with circumstellar material (CSM) during the first few days after explosion, implying that their red supergiant (RSG) progenitors experience episodic or eruptive mass loss. However, because it is difficult to discover SNe early, the diversity of CSM configurations in RSGs has not been fully mapped. SN 2021yja, first detected within approximate to 5.4 hours of explosion, shows some signatures of CSM interaction (high UV luminosity and radio and x-ray emission) but without the narrow emission lines or early light-curve peak that can accompany CSM. Here we analyze the densely sampled early light curve and spectral series of this nearby SN to infer the properties of its progenitor and CSM. We find that the most likely progenitor was an RSG with an extended envelope, encompassed by low-density CSM. We also present archival Hubble Space Telescope imaging of the host galaxy of SN 2021yja, which allows us to place a stringent upper limit of less than or similar to 9 M-circle dot; on the progenitor mass. However, this is in tension with some aspects of the SN evolution, which point to a more massive progenitor. Our analysis highlights the need to consider progenitor structure when making inferences about CSM properties, and that a comprehensive view of CSM tracers should be made to give a fuller view of the last years of RSG evolution.
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| 14. |
- Janko, Matthew, et al.
(författare)
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Contemporary Outcomes After Partial Resection of Infected Aortic Grafts
- 2021
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 76, s. 202-210
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed.RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01)CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.
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| 15. |
- Pearce, Neil E, et al.
(författare)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 16. |
- Peng, Shi-Yu, et al.
(författare)
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Reduced motor cortex GABABR function following chronic alcohol exposure
- 2021
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 26:2, s. 383-395
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Tidskriftsartikel (refereegranskat)abstract
- The GABA(B) receptor (GABA(B)R) agonist baclofen has been used to treat alcohol and several other substance use disorders (AUD/SUD), yet its underlying neural mechanism remains unclear. The present study aimed to investigate cortical GABA(B)R dynamics following chronic alcohol exposure. Ex vivo brain slice recordings from mice chronically exposed to alcohol revealed a reduction in GABA(B)R-mediated currents, as well as a decrease of GABA(B1/2)R and G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) activities in the motor cortex. Moreover, our data indicated that these alterations could be attributed to dephosphorylation at the site of serine 783 (ser-783) in GABA(B2) subunit, which regulates the surface expression of GABA(B)R. Furthermore, a human study using paired-pulse-transcranial magnetic stimulation (TMS) analysis further demonstrated a reduced cortical inhibition mediated by GABA(B)R in patients with AUD. Our findings provide the first evidence that chronic alcohol exposure is associated with significantly impaired cortical GABA(B)R function. The ability to promote GABA(B)R signaling may account for the therapeutic efficacy of baclofen in AUD.
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| 17. |
- Potapov, Anton M., et al.
(författare)
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Global fine-resolution data on springtail abundance and community structure
- 2024
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Ingår i: Scientific Data. - : Nature Publishing Group. - 2052-4463. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.
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| 18. |
- Young, WJ, et al.
(författare)
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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 1411-
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Tidskriftsartikel (refereegranskat)abstract
- The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
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