| 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. |
- 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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| 3. |
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| 4. |
- Wu, Jie, et al.
(författare)
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The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort : the Shanghai Aging Study
- 2024
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central (BMC). - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001).CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.
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| 5. |
- Ablikim, M., et al.
(författare)
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Amplitude analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:5, s. 052001-
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Tidskriftsartikel (refereegranskat)abstract
- We perform an analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot using a data set of 2.92 fb(-1) of e(+) e(-) collisions at the (3770) mass accumulated by the BESIII experiment, in which 166694 candidate events are selected with a background of 15.1%. The Dalitz plot is found to be well represented by a combination of six quasitwo- body decay channels [k(SP)(0)(+) (1450)(+,) ] plus a small nonresonant component. Using the fit fractions from this analysis, partial branching ratios are updated with higher precision than previous measurements.
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| 6. |
- Ablikim, M., et al.
(författare)
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Measurement of chi(cJ) decaying into eta ' K+K-
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:7, s. 074030-
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Tidskriftsartikel (refereegranskat)abstract
- Using (106.41 +/- 0.86) x 10(6) Psi(3686) events collected with the BESIII detector at BEPCII, we study for the first time the decay chi(cJ) -> eta'K+K- (J = 1, 2), where eta' -> gamma rho(0) and eta' -> eta pi(+)pi(-). A partial wave analysis in the covariant tensor amplitude formalism is performed for the decay chi(c1) -> eta'K+K-. Intermediate processes chi(c1) -> eta'f(2)'(1525) chi(c1) -> K-0*(1430)K-+/-(-/+) (K-0*(1430)(+/-) -> eta'K-+/-) are observed with statistical significances larger than 5 sigma, and their branching fractions are measured.
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| 7. |
- Ablikim, M., et al.
(författare)
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Measurement of the branching fraction for psi(3686) -> omega K+K-
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:11, s. 112006-
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Tidskriftsartikel (refereegranskat)abstract
- With 1.06 x 10(8) psi(3686) events collected with the BESIII detector, the branching fraction of psi(3686) -> omega K+K- is measured to be (1.54 +/- 0.04 +/- 0.11) x 10(-4). This is the most precise result to date, due to the largest psi(3686) sample, improved signal reconstruction efficiency, good simulation of the detector performance, and a more accurate knowledge of the continuum contribution. Using the branching fraction of J/psi -> omega K+K-, the ratio B(psi(3868) -> K+K-)/B(J/psi -> K+K-) is determined to be (18.4 +/- 3.7)%. This constitutes a significantly improved test of the 12% rule, with the uncertainty now dominated by the J/psi branching fraction.
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| 8. |
- Ablikim, M., et al.
(författare)
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Observation of e(+)e(-) -> gamma X(3872) at BESIII
- 2014
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:9, s. 092001-
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Tidskriftsartikel (refereegranskat)abstract
- With data samples collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energies from 4.009 to 4.420 GeV, the process e(+)e(-) -> gamma X(3872) is observed for the first time with a statistical significance of 6.3 sigma. The measured mass of the X(3872) is (3871.9 +/- 0.7(stat) +/- 0.2(syst)) MeV/c(2), in agreement with previous measurements. Measurements of the product of the cross section sigma[e(+)e(-) -> gamma X(3872)] and the branching fraction B [X(3872) -> pi(+)pi(-)J/psi] at center-of-mass energies 4.009, 4.229, 4.260, and 4.360 GeV are reported. Our measurements are consistent with expectations for the radiative transition process Y(4260) -> gamma X(3872).
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| 9. |
- Ablikim, M., et al.
(författare)
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Observation of eta' -> pi(+) pi(-) pi(+) pi(-) and eta' -> pi(+) pi(-) pi(0) pi(0)
- 2014
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 112:25, s. 251801-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.3 x 10(9) J/psi events collected with the BESIII detector, we report the first observation of eta' -> pi(+) pi(-) pi(+) pi(-) and eta' -> pi(+) pi(-) pi(0) pi(0). The measured branching fractions are B(eta' -> pi(+) pi(-) pi(+) pi(-)) = [8.53 +/- 0.69(stat.) +/- 0.64(syst.)] x 10(-5) and B(eta' -> pi(+) pi(-) pi(0) pi(0)) = [1.82 +/- 0.35(stat.) +/- 0.18(syst.)] x 10(-4), which are consistent with theoretical predictions based on a combination of chiral perturbation theory and vector-meson dominance.
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| 10. |
- Ablikim, M., et al.
(författare)
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Observation of the decay psi(3686) -> Lambda(Sigma)over-bar(+/-) pi(-/+) + c.c
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112007-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1:06 X 10(8) psi(3686) events collected with the BESIII detector, we present the first observation of the decays of psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c. and psi(3686) -> Lambda(Sigma) over bar (-) pi(+) + c.c. The branching fractions are measured to be B(psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c.) = (1.40 +/- 0.03 +/- 0.13) X 10(-4) and B(psi(3686) -> Lambda (Sigma) over bar (-) pi(+) + c.c.) = (1.54 +/- 0.04 +/- 0.13) X 10(-4) where the first errors are statistical and the second ones systematic.
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| 11. |
- Ablikim, M., et al.
(författare)
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Precision measurement of the mass of the tau lepton
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:1
-
Tidskriftsartikel (refereegranskat)abstract
- An energy scan near the tau pair production threshold has been performed using the BESIII detector. About 24 pb(-1) of data, distributed over four scan points, were collected. This analysis is based on t pair decays to ee, e mu, eh, h, hh, e.,. and p. final states, where h denotes a charged p or K. The mass of the t lepton is measured from a maximum likelihood fit to the t pair production cross- section data to be m(tau) = 1776.91 +/- 0.12_0.10 - 0.13 _ MeV/c(2), which is currently the most precise value in a single measurement.
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| 12. |
- Ablikim, M., et al.
(författare)
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Search for eta(c)(2S)h(c) -> p(p)over-bar decays and measurements of the chi(cJ) -> p(p)over-bar branching fractions
- 2013
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112001-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.06 x 10(8)psi(3686) events collected with the BESIII detector at BEPCII, the decays eta(c)(2S) -> p (p) over bar and h(c) -> p (p) over bar are searched for, where eta(c)(2S) and h(c) are reconstructed in the decay chains psi(3686) -> gamma eta(c)(2S), eta(c)(2S) -> p (p) over bar and psi(3686) -> pi(0)h(c), h(c) -> p (p) over bar, respectively. No significant signals are observed. The upper limits of the product branching fractions are determined to be B(psi(3686) -> gamma eta(c)(2S)) x B(eta(c)(2S) -> p (p) over bar) < 1.4 x 10(-6) and B(psi(3686) -> pi(0)h(c)) x B(h(c) -> p<(p)over bar>) < 1.3 x 10(-7) at the 90% C.L.. The branching fractions for chi(cJ) -> p<(p)over bar> (J = 0, 1, 2) are also measured to be (24.5 +/- 0.8 +/- 1.3, 8.6 +/- 0.5 +/- 0.5, 8.4 +/- 0.5 +/- 0.5) x 10(-5), which are the world's most precise measurements.
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| 13. |
- Ablikim, M., et al.
(författare)
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Search for the radiative transitions Psi(3770) -> gamma eta(c) and gamma eta(c) (2S)
- 2014
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:11, s. 112005-
-
Tidskriftsartikel (refereegranskat)abstract
- By using a 2.92 fb-1 data sample taken at pffisffiffi 3.773 GeV with the BESIII detector operating at the BEPCII collider, we search for the radiative transitions.d3770c and cd2S through the hadronic decays cdcd2S. K0 SK p. No significant excess of signal events above background is observed. We set upper limits at a 90% confidence level for the product branching fractions to be Bdd3770cxBd.c. K0 SK k p < 1.6x10-5 and Bd.d3770cd2SxBd.cd2S. K0 SK p<5.6x10-6. Combining our result with world-average values of Bd.cd.cd2S. K0 SK p, we find the branching fractions Bd.d3770c< 6.8 x 10-4 and Bd.d3770cd2S< 2.0 x 10-3 at a 90% confidence level.
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| 14. |
- Ablikim, M., et al.
(författare)
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Search for the rare decays J/y -> D-s(-) rho(+) and J/psi -> <(D)over bar(0)<(K)over bar*(0)
- 2014
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 89:7, s. 071101-
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Tidskriftsartikel (refereegranskat)abstract
- A search for the rare decays of J/psi -> D-S(-) rho(+) + c.c. and J/psi -> <(D)over bar(0)<(K)over bar*(0) + c.c. is performed with a data sample of 225.3-million J/psi events collected with the Beijing Spectrometer III detector. No evident signal is observed. Upper limits on the branching fractions are determined to be beta(J/psi -> D-S(-)rho(+) + c.c.) < 1.3 x 10(-5) and beta(J/psi -> <(D)over bar(0)<(K)over bar*(0) + c.c.) < 2.5 x 10(-6) at the 90% confidence level.
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| 15. |
- Ablikim, M., et al.
(författare)
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Study of e(+)e(-) -> p(p)over-bar in the vicinity of psi(3770)
- 2014
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 735, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- Using 2917 pb(-1) of data accumulated at 3.773 GeV, 44.5 pb(-1) of data accumulated at 3.65 GeV and data accumulated during a psi(3770) line-shape scan with the BESIII detector, the reaction e(+)e(-) -> p (p) over bar is studied considering a possible interference between resonant and continuum amplitudes. The cross section of e(+)e(-) -> psi(3770) -> p (p) over bar, sigma(e(+)e(-)-> psi(3770) -> p (p) over bar), is found to have two solutions, determined to be (0.059(-0.020)(+0.070) +/- 0.012) pb with the phase angle phi = (255.8(-26.6)(+39.0) +/- 4.8). (< 0.166 pb at the 90% confidence level), or sigma(e(+)e(-) -> psi(3770) -> p<(p)over bar>) = (2.57(-0.13)(+0.12) +/- 0.12) pb with phi = (266.9(-6.3)(+6.1) +/- 0.9)degrees both of which agree with a destructive interference. Using the obtained cross section of psi(3770) -> p (p) over bar, the cross section of p (p) over bar -> psi(3770), which is useful information for the future PANDA experiment, is estimated to be either (9.8(-3.9)(+11.8)) nb (< 27.5 nb at 90% C.L.) or (425.6(-43.7)(+42.9)) nb. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.
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| 16. |
- Ablikim, M., et al.
(författare)
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Study of e(+)e(-) -> p(p)over-bar pi(0) in the vicinity of the psi(3770)
- 2014
-
Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 90:3, s. 032007-
-
Tidskriftsartikel (refereegranskat)abstract
- The process e(+)e(-) -> p (p) over bar pi(0) has been studied by analyzing data collected at root s = 3.773 GeV, root s = 3.650 GeV, and during a psi(3770) line shape scan with the BESIII detector at the BEPCII collider. The Born cross section of p (p) over bar pi(0) in the vicinity of the psi(3770) is measured, and the Born cross section of psi(3770) -> p (p) over bar pi(0) is extracted considering interference between resonant and continuum production amplitudes. Two solutions with the same probability and a significance of 1.5 sigma are found. The solutions for the Born cross section of psi(3770) -> p (p) over bar pi(0) are 33.8 +/- 1.8 +/- 2.1 pb and 0.06(-0.04-0.01)(+0.10+0.01) pb (< 0.22 pb at a 90% confidence level). Using the estimated cross section and a constant decay amplitude approximation, the cross section sigma(p<(p)over bar> -> psi(3770)pi(0)) is calculated for the kinematic situation of the planned (p) over bar ANDA experiment. The maximum cross section corresponding to the two solutions is expected to be less than 0.79 nb at 90% confidence level and 122 +/- 10 nb at a center-of-mass energy of 5.26 GeV.
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| 17. |
- Adams, Marc A., et al.
(författare)
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Patterns of neighborhood environment attributes related to physical activity across 11 countries : a latent class analysis
- 2013
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants' response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA. Methods: A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 +/- 12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U. S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10-15 minutes walk of participants' residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants' response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country. Results: A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, "Overall Activity Supportive (52% of sample)", "High Walkable and Unsafe with Few Recreation Facilities (16%)", "Safe with Active Transport Facilities (12%)", "Transit and Shops Dense with Few Amenities (15%)", and "Safe but Activity Unsupportive (5%)". Country representation differed by type (e. g., U. S. disproportionally represented "Safe but Activity Unsupportive"). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR=2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR=1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA. Conclusions: Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
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| 18. |
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| 19. |
- Braunerhjelm, Pontus, et al.
(författare)
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Does Labour Mobility Foster Innovation? : Evidence from Sweden
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- By utilising a Swedish unique, matched employer-employee dataset that has been pooled with firm-level patent application data, we provide new evidence that knowledge workers’ mobility has a positive and strongly significant impact on firm innovation output, as measured by firm patent applications. The effect is particularly strong for knowledge workers that have previously worked in a patenting firm (the learning-by-hiring effect), but firms losing a knowledge worker are also shown to benefit (the diaspora effect), albeit more weakly. Finally, the effect is more pronounced when the joining worker originates in another region.
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| 20. |
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| 21. |
- Braunerhjelm, Pontus, et al.
(författare)
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Labour as a knowledge carrier : how increased mobilityinfluences entrepreneurship
- 2015
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Ingår i: Journal of Technology Transfer. - : Springer-Verlag New York. - 0892-9912 .- 1573-7047. ; 41:6, s. 1308-1326
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Tidskriftsartikel (refereegranskat)abstract
- According to the knowledge-based spillover theory of entrepreneurship (KSTE), entrepreneurship is positively associated with the knowledge endowment level. An increase in knowledge expands the opportunity set, which is then exploited by heterogeneous entrepreneurs. The objective of this paper is to empirically test the validity of the KSTE by employing a detailed database comprising more than 19 million observations for the period 2001–2008 at the level of individuals, firms and regions in Sweden. Knowledge is claimed to be partly embodied in labour, implying that an increase in labour mobility can be expected to influence knowledge endowment at the regional level. Our dependent variable is an individual who has remained in a region throughout the time period considered. Controlling for a number of other variables, inter-regional labour inflows and intra-regional mobility levels are shown to exert a strong positive effect on entrepreneurship. This contrasts with inter-regional outflows, which negatively affect entrepreneurial entry. Another noteworthy result is that the probability of exploiting an increased knowledge stock through entrepreneurship increases by 15 % points if the individual has previous experience in starting a firm.
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| 22. |
- Braunerhjelm, Pontus, 1953-, et al.
(författare)
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Labour market mobility, knowledge diffusion and innovation
- 2020
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Ingår i: European Economic Review. - : Elsevier B.V.. - 0014-2921 .- 1873-572X. ; 123
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Tidskriftsartikel (refereegranskat)abstract
- Utilising a unique Swedish matched employer–employee dataset, which has been pooled with firm-level patent application data, we provide new evidence that knowledge workers’ mobility has a positive and strongly significant impact on firm innovation output, as measured by firm patent applications. The effect is statistically and economically highly significant for knowledge workers who have previously worked in a patenting firm (the learning-by-hiring effect), whereas only limited impact could be detected for firms losing knowledge workers (the learning-by-diaspora effect). No effects were detected for inexperienced university graduates. Finally, the effect is more pronounced when the joining worker originates from within the same region. © 2020 Elsevier B.V.
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| 23. |
- Braunerhjelm, Pontus, 1953-, et al.
(författare)
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The knowledge spillover theory of intrapreneurship
- 2017
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Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913.
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Tidskriftsartikel (refereegranskat)abstract
- Introducing the Knowledge Spillover Theory of Intrapreneurship, we examine how labour mobility impacts innovation distributed by firm size. A matched employer-employee dataset, pooled with firm-level patent application data, is implemented in the analysis. We provide new evidence that knowledge workers’ mobility has a positive and strongly significant impact on all firms’ innovation output, measured as patent applications. The patterns and effects do however differ between large and small firms. More precisely, for small firms, intraregional mobility of knowledge workers who have previously worked in a patenting firm (the learning-by-hiring effect) is shown to be statistically and economically highly significant, whereas only limited impact could be detected for firms losing knowledge workers (the learning-by-diaspora effect).
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| 24. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 25. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 26. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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Is Olfactory Impairment Associated With 10-year Mortality Mediating by Neurodegenerative Diseases in Older Adults? The Four-Way Decomposition Analysis
- 2021
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Literature shows that olfactory impairment (OI) is associated not only with neurodegenerative diseases (NDDs), but also with increased mortality. In this study, we analyzed data collected from the prospective phase of the 10-year follow-up of the Shanghai Aging Study (SAS) to explore the mediation effect of NDDs on the OI-mortality relationship.Methods: We analyzed data collected from the prospective phase of the 10-year follow-up of the SAS. We included 1,811 participants aged 60 years or older who completed both an olfactory identification test and a cognitive assessment at baseline (2010-2011). Survival status of the participants from baseline to December 31, 2019 was obtained from the local mortality surveillance system. We used the four-way decomposition method to attribute effects to interaction and mediation and to explore the mediation effect of NDDs on the OI-mortality relationship.Results: The four-way decomposition method revealed a statistically significant association of OI with death. Overall, 43% higher risk for death was associated with OI [excess relative risk (ERR) = 0.43, 95% CI: 0.06-0.80, p = 0.023]. Excluding the mediation from NDDs and interaction between OI and NDDs, the controlled direct effect of OI on death was even higher in NDDs participants, with an ERR of 77% (95% CI: 0.00-1.55, p = 0.050). Statistically significant association was found for failure to identify coffee (ERR = 0.77, 95% CI: 0.18-1.36, p = 0.010) and marginally significant associations were found for failure to identify cinnamon (ERR = 0.33, 95% CI: -0.02-0.68, p = 0.068) and rose (ERR = 0.33, 95% CI: -0.01-0.67, p = 0.054) with death.Conclusion: OI was associated with the long-term mortality in older adults and the association was even stronger in those with NDDs. Failure to identify coffee or rose was associated with a higher mortality risk, and the association was mediated by NDDs.
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| 27. |
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| 28. |
- Chen, DS, et al.
(författare)
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Single cell atlas for 11 non-model mammals, reptiles and birds
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 7083-
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Tidskriftsartikel (refereegranskat)abstract
- The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Ding, B.F., et al.
(författare)
-
Electroluminescence and magnetoresistance of the organic light-emitting diode with a La0.7 Sr0.3 Mn O3 anode
- 2008
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 93:18
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Tidskriftsartikel (refereegranskat)abstract
- Electroluminescence (EL) with brightness up to 300 cd m2 is observed from organic light-emitting diodes fabricated on oxygen-treated La0.7 Sr0.3 Mn O 3 anodes. An external magnetic field of 150 mT applied parallel to the device surface can enhance the EL intensity by 10%, accompanied by a raised current efficiency. In-plane magnetization of the ferromagnetic anode is found to be the main origin of increase in the current contributable to EL, though magnetoresistance of the organic functional materials also plays a role in the EL enhancement observed in the magnetic field. © 2008 American Institute of Physics.
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| 33. |
- Ding, Bao Jian, et al.
(författare)
-
Biosynthesis of the sex pheromone component (E,Z)-7,9-Dodecadienyl acetate in the European Grapevine Moth, Lobesia botrana, involving ∆11 desaturation and an elusive ∆7 desaturase
- 2021
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Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 47:3, s. 248-264
-
Tidskriftsartikel (refereegranskat)abstract
- The European grapevine moth, Lobesia botrana, uses (E,Z)-7,9-dodecadienyl acetate as its major sex pheromone component. Through in vivo labeling experiments we demonstrated that the doubly unsaturated pheromone component is produced by ∆11 desaturation of tetradecanoic acid, followed by chain shortening of (Z)-11-tetradecenoic acid to (Z)-9-dodecenoic acid, and subsequently introduction of the second double bond by an unknown ∆7 desaturase, before final reduction and acetylation. By sequencing and analyzing the transcriptome of female pheromone glands of L. botrana, we obtained 41 candidate genes that may be involved in sex pheromone production, including the genes encoding 17 fatty acyl desaturases, 13 fatty acyl reductases, 1 fatty acid synthase, 3 acyl-CoA oxidases, 1 acetyl-CoA carboxylase, 4 fatty acid transport proteins and 2 acyl-CoA binding proteins. A functional assay of desaturase and acyl-CoA oxidase gene candidates in yeast and insect cell (Sf9) heterologous expression systems revealed that Lbo_PPTQ encodes a ∆11 desaturase producing (Z)-11-tetradecenoic acid from tetradecanoic acid. Further, Lbo_31670 and Lbo_49602 encode two acyl-CoA oxidases that may produce (Z)-9-dodecenoic acid by chain shortening (Z)-11-tetradecenoic acid. The gene encoding the enzyme introducing the E7 double bond into (Z)-9-dodecenoic acid remains elusive even though we assayed 17 candidate desaturases in the two heterologous systems.
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| 34. |
- Ding, Ding, et al.
(författare)
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Can dementia be predicted using olfactory identification test in the elderly? A Bayesian network analysis
- 2020
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Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279 .- 2162-3279. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous studies suggest that olfactory dysfunction is associated with cognitive decline or dementia.OBJECTIVE: To find a potential association between the olfactory identification (OI) and dementia onset, and build a prediction model for dementia screening in the older population.METHODS: Nine hundred and forty-seven participants from the Shanghai Aging Study were analyzed. The participants were dementia-free and completed OI test using the Sniffin' Sticks Screening Test-12 at baseline. After an average of 4.9-year follow-up, 75 (8%) of the participants were diagnosed with incident dementia. Discrete Bayesian network (DBN) and multivariable logistic regression (MLR) models were used to explore the dependencies of the incident dementia on the baseline demographics, lifestyles, and OI test results.RESULTS: In DBN analysis, odors of orange, cinnamon, peppermint, and pineapple, combined with age and Mini-mental State Examination (MMSE), achieved a high predictive ability for incident dementia, with an area under the receiver operating characteristic curve (AUC) larger than 0.8. The odor cinnamon showed the highest AUC of 0.838 (95% CI: 0.731-0.946) and a high accuracy of 0.867. The DBN incorporating age, MMSE, and one odor test had an accuracy (0.760-0.872 vs. 0.835) comparable to that of the MLR model and revealed the dependency between the variables.CONCLUSION: The DBN using OI test may have predictive ability comparable to MLR analysis and suggest potential causal relationship for further investigation. Identification of odor cinnamon might be a useful indicator for dementia screening and deserve further investigation.
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| 35. |
- Ding, Ding, et al.
(författare)
-
Cholesterol profiles and incident cognitive decline among older adults : the Shanghai Aging Study
- 2021
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 50:2, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: the association between cholesterol profiles and risk of cognitive decline among older adults was inconclusive.OBJECTIVE: to examine the association between cholesterol profiles and risk of cognitive decline in older adults with or without vascular risk factors (VRFs) in the prospective phase of the Shanghai Aging Study.DESIGN: a prospective community-based cohort study.SETTING: Shanghai, China.PARTICIPANTS: we prospectively followed 1,556 dementia-free participants aged ≥60 years with a baseline cholesterol profile for 5.2 years on average. Participants with at least one of obesity, diabetes, hypertension, stroke, and coronary artery disease were categorised to the VRFs group, and those free of any VRFs were categorised to the non-VRFs group.METHODS: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol in serum were measured at baseline. At follow-up, consensus diagnosis of incident dementia and Alzheimer's disease (AD) were established based on medical, neurological, and neuropsychological examinations. Cox regression was used to assess the association between cholesterol and incident dementia/AD; multivariate linear regression was used to examine the relationship between cholesterol and an annual rate of Mini Mental State Examination (MMSE) score decline in participants with or without VRFs.RESULTS: among VRFs-free participants, TC (HR 0.62, 95%CI 0.40-0.95) and LDL-C (HR 0.47, 95%CI 0.28-0.80) were inversely associated with incident dementia, LDL-C was inversely associated with incident AD (HR 0.50, 95%CI 0.28-0.90). A significant correlation was found between incremental TC (β = 0.08), LDL-C (β = 0.09), and a slower annual decline of MMSE score.CONCLUSIONS: effect of cholesterol on cognitive decline may be modified by VRFs.
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| 36. |
- Ding, Ding, 1986-, et al.
(författare)
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Does Innovation Lead to Firm Growth? : Explorative versus Exploitative Innovations
- 2016
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we examine the relationship between innovation and firm growth. Weimplement a classification of innovations based on whether they are explorative orexploitative, taking advantage of a unique Swedish dataset for the period 1997 to 2012.The data allow us to construct each firm’s innovation history. Panel regression estimations,together with an instrumental variable method, confirm a significant and positive effect ofboth exploitative and explorative innovation on firms’ employment growth. More radicalexplorative innovations are shown to have a more persistent growth effect, whereasexploitative innovation increases labour demand in the short run. We also provideempirical findings regarding the effect of innovations distributed on size classes anddifferent ownership structures.
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| 37. |
- Ding, Ding, 1986-
(författare)
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Heterogeneous Innovation and Labour Mobility
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge is a necessary and critically important factor in generating growth and increased prosperity. The extent to which such effects are materialized depends however on its diffusion and how it transcends into innovation, entrepreneurship and growing firms. This doctoral thesis consists of four papers that examine how labor mobility and innovation strategies influence the performance at the firm level with respect to new ventures, firm level growth and innovativeness. The first paper provides empirical support of the validity of the knowledge-based spillover theory of entrepreneurship by employing a detailed database. The results indicate that both inter-regional labor inflows and intra-regional labor mobility exert a strong positive effect on entrepreneurship, while inter-regional outflows negatively affect entrepreneurial entry. The second paper examines the influence of the labor mobility of knowledge workers on innovation at the firm level. New evidence are provided that reveals a positive and significant impact of labor mobility on firms’ innovations measured as patent applications. In the third paper the influence of labor mobility between multinational enterprises (MNEs) and other firms on innovation is investigated. Looking at firms having different owner structures, empirical evidence are provided that particularly domestically owned MNEs generate strong knowledge spillovers to non-MNEs that translates into innovations. The fourth paper examines the relationship between innovation and firm growth. We implement a classification of innovations based on whether they are explorative or exploitative. The more radical explorative innovations are shown to have a persistent growth effect in the long term, while exploitative innovation increases the labor demand predominantly in the short term.
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| 38. |
- Ding, Ding, 1986-
(författare)
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Learning from Multinational Enterprises:Knowledge flows through labour mobility
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Labour mobility is one mechanism through which technology and innovation frommultinational enterprises (MNEs) may be transferred to non-multinational enterprises(non-MNEs). Previous research has predominantly focused on such transfers as MNEsfrom developed economies have located to less developed countries. The objective of thispaper is to investigate how labour mobility between MNEs and other firms in a developedeconomy impacts innovation. Using employer-employee panel data on Swedish firms overa 10-year period, we find empirical evidence that spillover through hiring workerspreviously employed at MNEs, particularly domestically owned MNEs, stimulatesinnovations, as measured by patent applications.
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| 39. |
- Ding, Ding, et al.
(författare)
-
Perceived neighborhood environment and physical activity in 11 countries : Do associations differ by country?
- 2013
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increasing empirical evidence supports associations between neighborhood environments and physical activity. However, since most studies were conducted in a single country, particularly western countries, the generalizability of associations in an international setting is not well understood. The current study examined whether associations between perceived attributes of neighborhood environments and physical activity differed by country. Methods: Population representative samples from 11 countries on five continents were surveyed using comparable methodologies and measurement instruments. Neighborhood environment x country interactions were tested in logistic regression models with meeting physical activity recommendations as the outcome, adjusted for demographic characteristics. Country-specific associations were reported. Results: Significant neighborhood environment attribute x country interactions implied some differences across countries in the association of each neighborhood attribute with meeting physical activity recommendations. Across the 11 countries, land-use mix and sidewalks had the most consistent associations with physical activity. Access to public transit, bicycle facilities, and low-cost recreation facilities had some associations with physical activity, but with less consistency across countries. There was little evidence supporting the associations of residential density and crime-related safety with physical activity in most countries. Conclusion: There is evidence of generalizability for the associations of land use mix, and presence of sidewalks with physical activity. Associations of other neighborhood characteristics with physical activity tended to differ by country. Future studies should include objective measures of neighborhood environments, compare psychometric properties of reports across countries, and use better specified models to further understand the similarities and differences in associations across countries.
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| 40. |
- Ding, Ding, et al.
(författare)
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Predictive Value of Odor Identification for Incident Dementia : The Shanghai Aging Study
- 2020
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media S.A.. - 1663-4365. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to evaluate the value of odors in the olfactory identification (OI) test and other known risk factors for predicting incident dementia in the prospective Shanghai Aging Study.Methods: At baseline, OI was assessed using the Sniffin' Sticks Screening Test 12, which contains 12 different odors. Cognition assessment and consensus diagnosis were conducted at both baseline and follow-up to identify incident dementia. Four different multivariable logistic regression (MLR) models were used for predicting incident dementia. In the no-odor model, only demographics, lifestyle, and medical history variables were included. In the single-odor model, we further added one single odor to the first model. In the full model, all 12 odors were included. In the stepwise model, the variables were selected using a bidirectional stepwise selection method. The predictive abilities of these models were evaluated by the area under the receiver operating characteristic curve (AUC). The permutation importance method was used to evaluate the relative importance of different odors and other known risk factors.Results: Seventy-five (8%) incident dementia cases were diagnosed during 4.9 years of follow-up among 947 participants. The full and the stepwise MLR model (AUC = 0.916 and 0.914, respectively) have better predictive abilities compared with those of the no- or single-odor models. The five most important variables are Mini-Mental State Examination (MMSE) score, age, peppermint detection, coronary artery disease, and height in the full model, and MMSE, age, peppermint detection, stroke, and education in the stepwise model. The combination of only the top five variables in the stepwise model (AUC = 0.901 and sensitivity = 0.880) has as a good a predictive ability as other models.Conclusion: The ability to smell peppermint might be one of the useful indicators for predicting dementia. Combining peppermint detection with MMSE, age, education, and history of stroke may have sensitive and robust predictive value for dementia in older adults.
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| 41. |
- He, Shuai Feng, et al.
(författare)
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Multi-scale dynamics for a lean-burn spark ignition natural gas engine under low load conditions
- 2023
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Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 332
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the multi-scale dynamics of the combustion system in a lean-burn spark ignition natural gas engine using different gas injection timings (GIT). The in-cylinder pressure time series are measured, and the indicated mean effective pressure (IMEP) time series are calculated. The influence of GIT on the combustion system is investigated through wavelet analysis, multi-resolution analysis, and the return maps with the GIT covering from 0 to 90°CA after top dead center at the intake stage. Results show that the combustion system has multi-scale chaotic characteristics, and it is sensitive to the change of GIT. The unreasonable GIT will result in serious combustion variations. Meanwhile, the combustion instability of the engine evolves on multiple time scales, showing evident multi-scale oscillation characteristics. All the wavelet power spectrums (WPS) present the characteristics of intermittent short-time periodic oscillations and persistent large-scale periodic oscillations concealed inside the IMEP time series. When the GIT approaches the medium value, the persistence of large-scale periodic oscillations is weakened, while the characteristics of high-frequency intermittent oscillations are enhanced. Under all working conditions, the contribution rate of high-frequency signal D1 decomposed by the IMEP time series to the overall time series fluctuation is about 40% or even higher. The contribution rate of the signal D1 also increases with the aggravation of combustion instability. The return map structures of high-frequency signals D1 and D2 show bifurcation structures, and the bifurcation characteristics of the signal D1 are more evident under medium GIT conditions, indicating a certain correlation between the 2–8 engine cycles, and the correlation between the adjacent engine cycles is stronger. The deterministic relationship between the multiple engine cycles found can help in developing a more reasonable and efficient combustion control strategy, which provides a theoretical basis for improving the stability of a natural gas engine.
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| 42. |
- Holtermann, Andreas, et al.
(författare)
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24-Hour Physical Behavior Balance for Better Health for All: “The Sweet-Spot Hypothesis”
- 2021
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Ingår i: Sports Medicine - Open. - : Springer. - 2199-1170 .- 2198-9761. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- "Sit less-move more" has been the univocal advice to adults for better health. Predominantly, this advice is based on research of physical behaviors during leisure-time. A recent study among > 100,000 adults indicates a u-shaped association between leisure-time physical activity and risk for cardiovascular disease and mortality among adults in physically active occupations. This may be explained by the considerable difference in 24-h physical behaviors between adults in sedentary and physically active occupations. Thus, the advice "sit less-move more" might not be the best for health among adults in physically active occupations. To provide a scientific approach and encourage research on 24-h physical behaviors and health for those in physically active occupations, we propose the "Sweet-Spot Hypothesis." The hypothesis postulates that the "Sweet-Spot" of 24-h physical behaviors for better health differs between adults, depending on their occupation. Specifically, the hypothesis claims that the advice "sit less-move more" does not bring adults in physically active occupations toward their "Sweet-Spot" of 24-h physical behaviors for better health. The purpose of our paper is to encourage researchers to test this proposed hypothesis by describing its origin, its theoretical underpinning, approaches to test it, and practical implications. To promote health for all, and decrease social health inequalities, we see a great need for empirically testing the "Sweet-Spot Hypothesis." We propose the "Sweet-Spot Hypothesis" to encourage discussion, debates, and empirical research to expand our collective knowledge about the healthy "24-h physical behavior balance" for all.
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| 43. |
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| 44. |
- Liu, Qing, et al.
(författare)
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Unraveling the unique role of brown graphitic carbon nitride in robust CO2 photoreduction
- 2023
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Ingår i: Applied Surface Science. - : ELSEVIER. - 0169-4332 .- 1873-5584. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- Photocatalytic CO2 reduction is one of the important means to alleviate the energy crisis. In this work, an oxygen linked and brown graphitic carbon nitride (GACN) was successfully prepared by thermal polymerization after oil bath method. GACN introduced oxygen atoms on surface of BulkCN. Various characterizations of the material show that the prepared GACN has a different structure and higher photoelectronic activity compared to BulkCN. GACN possessed strong photocatalytic CO2 reduction capacity, and the photocatalytic activity was significantly improved compared with BulkCN. In view of density functional theory calculations, it is proved that the oxygen atoms introduced by GACN increase CO2 photoreaction reactivity, enhance electronic activity and reduce the reaction energy barrier. This work can have a positive effect on the photocatalytic application of g-C3N4 with the existence of oxygen atoms.
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| 45. |
- Olsen, Thale Kristin, et al.
(författare)
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DHODH is an independent prognostic marker and potent therapeutic target in neuroblastoma
- 2022
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Ingår i: JCI Insight. - : AMER SOC CLINICAL INVESTIGATION INC. - 2379-3708. ; 7:17
-
Tidskriftsartikel (refereegranskat)abstract
- Despite intensive therapy, children with high-risk neuroblastoma are at risk of treatment failure. We applied a multiomic system approach to evaluate metabolic vulnerabilities in human neuroblastoma. We combined metabolomics, CRISPR screening, and transcriptomic data across more than 700 solid tumor cell lines and identified dihydroorotate dehydrogenase (DHODH), a critical enzyme in pyrimidine synthesis, as a potential treatment target. Of note, DHODH inhibition is currently under clinical investigation in patients with hematologic malignancies. In neuroblastoma, DHODH expression was identified as an independent risk factor for aggressive disease, and high DHODH levels correlated to worse overall and event-free survival. A subset of tumors with the highest DHODH expression was associated with a dismal prognosis, with a 5-year survival of less than 10%. In xenograft and transgenic neuroblastoma mouse models treated with the DHODH inhibitor brequinar, tumor growth was dramatically reduced, and survival was extended. Furthermore, brequinar treatment was shown to reduce the expression of MYC targets in 3 neuroblastoma models in vivo. A combination of brequinar and temozolomide was curative in the majority of transgenic TH-MYCN neuroblastoma mice, indicating a highly active clinical combination therapy. Overall, DHODH inhibition combined with temozolomide has therapeutic potential in neuroblastoma, and we propose this combination for clinical testing.
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| 46. |
- Sun, Zhengyi, 1982-, et al.
(författare)
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Buffer-enhanced electron injection in organic light-emitting devices with copper cathode
- 2013
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Ingår i: Organic electronics. - Amsterdam : Elsevier. - 1566-1199 .- 1878-5530. ; 14:2, s. 511-515
-
Tidskriftsartikel (refereegranskat)abstract
- We explore in this work the use of Cu as a cathode material in organic light-emitting devices (OLEDs) and find a dual electron–injection enhancement mechanism derived from the LiF layer. Different from what observed previously in Ag- and Au-cathode devices, the LiF buffer layer in the Cu-cathode OLEDs starts to play its role in performance improvement when it is much thinner than 3 nm, the optimal value of buffer thickness, and in the case of optimal thickness, the device exhibits excellent performance comparable to conventional Al-cathode device. The phenomenon observed is ascribed to enhanced electron injection as a result of combined effect of interfacial reaction and tunneling barrier reduction mechanism: while chemical reaction plays a key role at the very beginning of interface formation, tunneling dominates in the subsequent stage leading to the tremendous improvement of the characteristics.
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| 47. |
- Tian, Jingyi, et al.
(författare)
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Active control of anapole states by structuring the phase-change alloy Ge2Sb2Te5
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- High-index dielectric nanoparticles supporting a distinct series of Mie resonances have enabled a new class of optical antennas with unprecedented functionalities. The great wealth of multipolar responses has not only brought in new physical insight but also spurred practical applications. However, how to make such a colorful resonance palette actively tunable is still elusive. Here, we demonstrate that the structured phase-change alloy Ge2Sb2Te5 (GST) can support a diverse set of multipolar Mie resonances with active tunability. By harnessing the dramatic optical contrast of GST, we realize broadband (del lambda/lambda similar to 15%) mode shifting between an electric dipole resonance and an anapole state. Active control of higher-order anapoles and multimodal tuning are also investigated, which make the structured GST serve as a multispectral optical switch with high extinction contrasts (>6 dB). With all these findings, our study provides a new direction for realizing active nanophotonic devices.
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| 48. |
- Van Asbroeck, Stephanie, et al.
(författare)
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Lifestyle and incident dementia: A COSMIC individual participant data meta-analysis
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279. ; 20:6, s. 3972-3986
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONThe LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODSWe combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTSA one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged <= 75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSIONModifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. Highlights A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.
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| 49. |
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| 50. |
- Wang, Fei, et al.
(författare)
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Endothelial cell heterogeneity and microglia regulons revealed by a pig cell landscape at single-cell level
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Pigs are valuable large animal models for biomedical and genetic research, but insights into the tissue- and cell-type-specific transcriptome and heterogeneity remain limited. By leveraging single-cell RNA sequencing, we generate a multiple-organ single-cell transcriptomic map containing over 200,000 pig cells from 20 tissues/organs. We comprehensively characterize the heterogeneity of cells in tissues and identify 234 cell clusters, representing 58 major cell types. In-depth integrative analysis of endothelial cells reveals a high degree of heterogeneity. We identify several functionally distinct endothelial cell phenotypes, including an endothelial to mesenchymal transition subtype in adipose tissues. Intercellular communication analysis predicts tissue- and cell type-specific crosstalk between endothelial cells and other cell types through the VEGF, PDGF, TGF-beta, and BMP pathways. Regulon analysis of single-cell transcriptome of microglia in pig and 12 other species further identifies MEF2C as an evolutionally conserved regulon in the microglia. Our work describes the landscape of single-cell transcriptomes within diverse pig organs and identifies the heterogeneity of endothelial cells and evolutionally conserved regulon in microglia.
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