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Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time dependent approach based on a contact angle distribution Niedermeier et al. (2014) and a modification of the parameterization presented in Hartmann et~al.~(2013) representing a time independent approach. The agreement between these and the measured data were good, i.e. they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice-active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice-active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice-active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty, the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time-dependent approach based on a contact angle distribution (Niedermeier et al., 2014) and a modification of the parameterization presented in Hartmann et al. (2013) representing a time-independent approach. The agreement between these and the measured data were good; i.e., they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative J/ψ decays, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a signal and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.7−48.5)×10−8 and (2.2−101.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
Background: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in childhood and a major cause of morbidity among children with pediatric rheumatic diseases. The management of JDM is very heterogeneous. The JDM working group of the Society for Pediatric Rheumatology (GKJR) aims to define consensus- and practice-based strategies in order to harmonize diagnosis, treatment and monitoring of JDM.
Methods: The JDM working group was established in 2015 consisting of 23 pediatric rheumatologists, pediatric neurologists and dermatologists with expertise in the management of JDM. Current practice patterns of management in JDM had previously been identified via an online survey among pediatric rheumatologists and neurologists. Using a consensus process consisting of online surveys and a face-to-face consensus conference statements were defined regarding the diagnosis, treatment and monitoring of JDM. During the conference consensus was achieved via nominal group technique. Voting took place using an electronic audience response system, and at least 80% consensus was required for individual statements.
Results: Overall 10 individual statements were developed, finally reaching a consensus of 92 to 100% regarding (1) establishing a diagnosis, (2) case definitions for the application of the strategies (moderate and severe JDM), (3) initial diagnostic testing, (4) monitoring and documentation, (5) treatment targets within the context of a treat-to-target strategy, (6) supportive therapies, (7) explicit definition of a treat-to-target strategy, (8) various glucocorticoid regimens, including intermittent intravenous methylprednisolone pulse and high-dose oral glucocorticoid therapies with tapering, (9) initial glucocorticoid-sparing therapy and (10) management of refractory disease.
Conclusion: Using a consensus process among JDM experts, statements regarding the management of JDM were defined. These statements and the strategies aid in the management of patients with moderate and severe JDM.
Using e+e− annihilation data sets corresponding to an integrated luminosity of 4.5 fb−1, collected with the BESIII detector at center-of-mass energies between 4.600 and 4.699 GeV, we report the first measurements of the absolute branching fractions B(Λ+c→pK0L)=(1.67±0.06±0.04)%, B(Λ+c→pK0Lπ+π−)=(1.69±0.10±0.05)%, and B(Λ+c→pK0Lπ0)=(2.02±0.13±0.05)%, where the first uncertainties are statistical and the second systematic. Combining with the known branching fractions of Λ+c→pK0S, Λ+c→pK0Sπ+π−, and Λ+c→pK0Sπ0, we present the first measurements of the K0S-K0L asymmetries R(Λ+c,K0S,LX)=B(Λ+c→K0SX)−B(Λ+c→K0LX)B(Λ+c→K0SX)+B(Λ+c→K0LX) in charmed baryon decays: R(Λ+c,pK0S,L)=−0.025±0.031, R(Λ+c,pK0S,Lπ+π−)=−0.027±0.048, and R(Λ+c,pK0S,Lπ0)=−0.015±0.046. No significant asymmetries within the uncertainties are observed.
Using (27.12±0.14)×108 ψ(3686) events collected with the BESIII detector at BEPCII, the decay of ψ(3686)→Ω−K+Ξ¯0+c.c. is observed for the first time. The branching fraction of this decay is measured to be Bψ(3686)→Ω−K+Ξ¯0+c.c.=(2.78±0.40±0.18)×10−6, where the first uncertainty is statistical and the second is systematic. Possible baryon excited states are searched for in this decay, but no evident intermediate state is observed with the current sample size.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
The Cabbibo-favored decay Λ+c→Ξ0K+π0 is studied for the first time using 6.1 fb−1 of e+e− collision data at center-of-mass energies between 4.600 and 4.840 GeV, collected with the BESIII detector at the BEPCII collider. With a double-tag method, the branching fraction of the three-body decay Λ+c→Ξ0K+π0 is measured to be (7.79±1.46±0.71)×10−3, where the first and second uncertainties are statistical and systematic, respectively. The branching fraction of the two-body decay Λ+c→Ξ(1530)0K+ is (5.99±1.04±0.29)×10−3, which is consistent with the previous result of (5.02±0.99±0.31)×10−3. In addition, the upper limit on the branching fraction of the doubly Cabbibo-suppressed decay Λ+c→nK+π0 is 7.1×10−4 at the 90% confidence level. The upper limits on the branching fractions of Λ+c→Σ0K+π0 and ΛK+π0 are also determined to be 1.8×10−3 and 2.0×10−3, respectively.
Observation of χcJ → 3(K⁺K⁻)
(2023)
By analyzing (27.12±0.14)×108 ψ(3686) events collected with the BESIII detector operating at the BEPCII collider, the decay processes χcJ→3(K+K−) (J=0,1,2) are observed for the first time with statistical significances of 8.2σ, 8.1σ, and 12.4σ, respectively. The product branching fractions of ψ(3686)→γχcJ, χcJ→3(K+K−) are presented and the branching fractions of χcJ→3(K+K−) decays are determined to be Bχc0→3(K+K−)=(10.7±1.8±1.1)×10−6, Bχc1→3(K+K−)=(4.2±0.9±0.5)×10−6, and Bχc2→3(K+K−)=(7.2±1.1±0.8)×10−6, where the first uncertainties are statistical and the second are systematic.
The process e+e−→Σ+Σ¯− is studied from threshold up to 3.04 GeV/c2 via the initial-state radiation technique using data with an integrated luminosity of 12.0 fb−1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of Σ are measured in eleven Σ+Σ¯− invariant mass intervals from threshold to 3.04 GeV/c2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays J/ψ→Σ+Σ¯− and ψ(3686)→Σ+Σ¯− are determined and the obtained results are consistent with the previous results of BESIII.
Using e+e− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy s√=3.773~GeV with the BESIII detector, a joint amplitude analysis is performed on the decays D0→π+π−π+π− and D0→π+π−π0π0(non-η). The fit fractions of individual components are obtained, and large interferences among the dominant components of D0→a1(1260)π, D0→π(1300)π, D0→ρ(770)ρ(770) and D0→2(ππ)S are found in both channels. With the obtained amplitude model, the CP-even fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are determined to be (75.2±1.1stat.±1.5syst.)% and (68.9±1.5stat.±2.4syst.)%, respectively. The branching fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are measured to be (0.688±0.010stat.±0.010syst.)% and (0.951±0.025stat.±0.021syst.)%, respectively. The amplitude analysis provides an important model for binning strategy in the measurements of the strong phase parameters of D0→4π when used to determine the CKM angle γ(ϕ3) via the B−→DK− decay.
Using e+e− annihilation data corresponding to an integrated luminosity of 2.93 fb−1 taken at the center-of-mass energy s√=3.773~GeV with the BESIII detector, a joint amplitude analysis is performed on the decays D0→π+π−π+π− and D0→π+π−π0π0(non-η). The fit fractions of individual components are obtained, and large interferences among the dominant components of D0→a1(1260)π, D0→π(1300)π, D0→ρ(770)ρ(770) and D0→2(ππ)S are found in both channels. With the obtained amplitude model, the CP-even fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are determined to be (75.2±1.1stat.±1.5syst.)% and (68.9±1.5stat.±2.4syst.)%, respectively. The branching fractions of D0→π+π−π+π− and D0→π+π−π0π0(non-η) are measured to be (0.688±0.010stat.±0.010syst.)% and (0.951±0.025stat.±0.021syst.)%, respectively. The amplitude analysis provides an important model for binning strategy in the measurements of the strong phase parameters of D0→4π when used to determine the CKM angle γ(ϕ3) via the B−→DK− decay.
Based on 4.5 fb−1 of e+e− collision data accumulated at center-of-mass energies between 4599.53 MeV and 4698.82 MeV with the BESIII detector, the decay Λ+c→nK0Sπ+π0 is observed for the first time with a significance of 9.2σ. The branching fraction is measured to be (0.85±0.13±0.03)%, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4σ. This indicates that there may be resonant contributions or some unknown dynamics in this decay.
The energy-dependent cross section for e+e−→ηψ(2S) is measured at eighteen center of mass energies from 4.288 GeV to 4.951 GeV using the BESIII detector. Using the same data samples, we also perform the first search for the reaction e+e−→ηX~(3872), but no evidence is found for the X~(3872) in the π+π−J/ψ mass distribution. At each of the eighteen center of mass energies, upper limits at the 90\% confidence level on the cross section for e+e−→ηψ(2S) and on the product of the e+e−→ηX~(3872) cross section with the branching fraction of X~(3872)→π+π−J/ψ are reported.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e+e−→η+X, normalized by the total cross section of e+e−→hadrons, is measured at eight center-of-mass energy points from 2.0000 GeV to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy from calculations with the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.
The absolute branching fraction of the decay Λc(2625)+→Λ+cπ+π− is measured for the first time to be (50.7±5.0stat.±4.9syst.)% with 368.48 pb−1 of e+e− collision data collected by the BESIII detector at the center-of-mass energies of s√=4.918 and 4.950 GeV. This result is lower than the naive prediction of 67\%, obtained from isospin symmetry, by more than 2σ, thereby indicating that the novel mechanism referred to as the \textit{threshold effect}, proposed for the strong decays of Λc(2595)+, also applies to Λc(2625)+. This measurement is necessary to obtain the coupling constants for the transitions between s-wave and p-wave charmed baryons in heavy hadron chiral perturbation theory. In addition, we search for the decay Λc(2595)+→Λ+cπ+π−. No significant signal is observed, and the upper limit on its branching fraction is determined to be 80.8\% at the 90\% confidence level.
Based on 4.5 fb−1 of e+e− collision data accumulated at center-of-mass energies between 4599.53 MeV and 4698.82 MeV with the BESIII detector, the decay Λ+c→nK0Sπ+π0 is observed for the first time with a significance of 9.2σ. The branching fraction is measured to be (0.85±0.13±0.03)%, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4σ. This indicates that there may be resonant contributions or some unknown dynamics in this decay.
By analyzing (27.12±0.14)×108 ψ(3686) events accumulated with the BESIII detector, the decay ηc(2S)→K+K−η is observed for the first time with a significance of 6.2σ after considering systematic uncertainties. The product of the branching fractions of ψ(3686)→γηc(2S) and ηc(2S)→K+K−η is measured to be B(ψ(3686)→γηc(2S))×B(ηc(2S)→K+K−η)=(2.39±0.32±0.34)×10−6, where the first uncertainty is statistical, and the second one is systematic. The branching fraction of ηc(2S)→K+K−η is determined to be B(ηc(2S)→K+K−η)=(3.42±0.46±0.48±2.44)×10−3, where the third uncertainty is due to the branching fraction of ψ(3686)→γηc(2S). Using a recent BESIII measurement of B(ηc(2S)→K+K−π0), we also determine the ratio between the branching fractions of ηc(2S)→K+K−η and ηc(2S)→K+K−π0 to be 1.49±0.22±0.25, which is consistent with the previous result of BaBar at a comparable precision level.
Model-independent determination of the strong-phase difference between D⁰ and D̄⁰ → π⁺π⁻π⁺π⁻ decays
(2024)
Measurements of the strong-phase difference between D0 and D¯0→π+π−π+π− are performed in bins of phase space. The study exploits a sample of quantum-correlated DD¯ mesons collected by the BESIII experiment in e+e− collisions at a center-of-mass energy of 3.773~GeV, corresponding to an integrated luminosity of 2.93~fb−1. Here, D denotes a neutral charm meson in a superposition of flavor eigenstates. The reported results are valuable for measurements of the CP-violating phase γ (also denoted ϕ3) in B±→DK±, D→π+π−π+π− decays, and the binning schemes are designed to provide good statistical sensitivity to this parameter. The expected uncertainty on γ arising from the precision of the strong-phase measurements, when applied to very large samples of B-meson decays, is around 1.5∘ or 2∘, depending on the binning scheme. The binned strong-phase parameters are combined to give a value of F4π+=0.746±0.010±0.004 for the CP-even fraction of D0→π+π−π+π− decays, which is around 30\% more precise than the previous best measurement of this quantity.
A search has been performed for the semileptonic decays D0→K0SK−e+νe, D+→K0SK0Se+νe and D+→K+K−e+νe, using 7.9 fb−1 of e+e− annihilation data collected at the center-of-mass energy s√=3.773 GeV by the BESIII detector operating at the BEPCII collider. No significant signals are observed, and upper limits are set at the 90\% confidence level of 2.13×10−5, 1.54×10−5 and 2.10×10−5 for the branching fractions of D0→K0SK−e+νe, D+→K0SK0Se+νe and D+→K+K−e+νe, respectively.
Observation of χcJ → 3(K⁺K⁻)
(2024)
By analyzing (27.12±0.14)×108 𝜓(3686) events collected with the BESIII detector operating at the BEPCII collider, the decay processes 𝜒𝑐𝐽→3(𝐾+𝐾−) (𝐽=0, 1, 2) are observed for the first time with statistical significances of 8.2𝜎, 8.1𝜎, and 12.4𝜎, respectively. The product branching fractions of 𝜓(3686)→𝛾𝜒𝑐𝐽, 𝜒𝑐𝐽→3(𝐾+𝐾−) are presented and the branching fractions of 𝜒𝑐𝐽→3(𝐾+𝐾−) decays are determined to be ℬ𝜒𝑐0→3(𝐾+𝐾−)=(10.7±1.8±1.1)×10−6, ℬ𝜒𝑐1→3(𝐾+𝐾−)=(4.2±0.9±0.5)×10−6, and ℬ𝜒𝑐2→3(𝐾+𝐾−)=(7.2±1.1±0.8)×10−6, where the first uncertainties are statistical and the second are systematic.
Based on 368.5 pb−1 of 𝑒+𝑒− collision data collected at center-of-mass energies 4.914 and 4.946 GeV by the BESIII detector, the 𝑒+𝑒−→𝜙𝜒𝑐1(3872) process is searched for the first time. No significant signal is observed and the upper limits at the 90% confidence level on the product of the Born cross section 𝜎(𝑒+𝑒−→𝜙𝜒𝑐1(3872)) and the branching fraction ℬ[𝜒𝑐1(3872)→𝜋+𝜋−𝐽/𝜓] at 4.914 and 4.946 GeV are set to be 0.85 and 0.96 pb, respectively. These measurements provide useful information for the production of the 𝜒𝑐1(3872) at 𝑒+𝑒− colliders and deepen our understanding about the nature of this particle.
The branching fraction of D+→K0Sπ0e+νe is measured for the first time using 7.93 fb−1 of e+e− annihilation data collected at the center-of-mass energy s√=3.773~GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B(D+→K0Sπ0e+νe) = (0.881 ± 0.017stat. ± 0.016syst.)\%. Based on an analysis of the D+→K0Sπ0e+νe decay dynamics, we observe the S-wave and P-wave components with fractions of fS-wave = (6.13 ± 0.27stat. ± 0.30syst.)% and fK¯∗(892)0 = (93.88 ± 0.27stat. ± 0.29syst.)\%, respectively. From these results, we obtain the branching fractions B(D+→(K0Sπ0)S-wave e+νe) = (5.41 ± 0.35stat. ± 0.37syst.)×10−4 and B(D+→K¯∗(892)0e+νe) = (4.97 ± 0.11stat. ± 0.12syst.)\%. In addition, the hadronic form-factor ratios of D+→K¯∗(892)0e+νe at q2=0, assuming a single-pole dominance parameterization, are determined to be rV=V(0)A1(0)=1.43 ± 0.07stat. ± 0.03syst. and r2=A2(0)A1(0)=0.72 ± 0.06stat. ± 0.02syst.
We perform the first investigation of the process e+e−→K+K−ψ(2S) and report its Born cross sections over a range of center-of-mass energies from 4.699 to 4.951~GeV. The measurements are carried out using several partial reconstruction techniques using data samples collected by the BESIII detector with a total integrated luminosity of 2.5~fb−1. We search for new tetraquark candidates Z±cs in the decays Z±cs→K±ψ(2S). No significant Z±cs signals are observed.
Using (2.712±0.014)×109 ψ(3686) events collected with the BESIII detector operating at the BEPCII, we find an evidence of the ηc(2S)→K+K−η′ decay with a statistical significance of 3.1σ. Its decay branching fraction is measured to be (12.24±4.60(stat.)±2.37(syst.)±4.68(extr.))×10−4, where the first uncertainty is statistical, the second is systematic, and the third uncertainty is from the branching fraction of the ψ(3686)→γηc(2S) decay. The upper limit on the product branching fraction B[ψ(3686)→γηc(2S)]× B[ηc(2S)→K+K−η′] is set to be 1.14×10−6 at 90% confidence level. In addition, the branching fractions of χc1→K+K−η′ and χc2→K+K−η′ are updated to be (8.47±0.09(stat.)±0.47(syst.))×10−4 and (1.53±0.04(stat.)±0.08(syst.))×10−4, respectively. The precision is improved by twofold.
Using (2712±14) × 106 ψ(2S) events collected with the BESIII detector at the BEPCII collider, we search for the decays ηc(2S)→ωω and ηc(2S)→ωϕ via the process ψ(2S)→γηc(2S). Evidence of ηc(2S)→ωω is found with a statistical significance of 3.2σ. The branching fraction is measured to be B(ηc(2S)→ωω)=(5.65±3.77(stat.)±5.32(syst.))×10−4. No statistically significant signal is observed for the decay ηc(2S)→ωϕ. The upper limit of the branching fraction at the 90\% confidence level is determined to be B(ψ(2S)→γηc(2S),ηc(2S)→ωϕ)<2.24×10−7. We also update the branching fractions of χcJ→ωω and χcJ→ωϕ decays via the ψ(2S)→γχcJ transition. The branching fractions are determined to be B(χc0→ωω)=(10.63±0.11±0.46)×10−4, B(χc1→ωω)=(6.39±0.07±0.29)×10−4, B(χc2→ωω)=(8.50±0.08±0.38)×10−4, B(χc0→ωϕ)=(1.18±0.03±0.05)×10−4, B(χc1→ωϕ)=(2.03±0.15±0.12)×10−5, and B(χc2→ωϕ)=(9.37±1.07±0.59)×10−6, where the first uncertainties are statistical and the second are systematic.
Search for X(3872)→π⁰π⁰χc₁,₂
(2024)
Using 10.1 fb−1 of e+e− collision data collected by the BESIII detector with center-of-mass energies between 4.15 GeV and 4.30 GeV, we search for the decays X(3872)→π0π0χc1,2, where the X(3872) is produced in e+e−→γX(3872). No evidence above 3σ is found for either decay. Upper limits at the 90% C.L. on the branching fractions of X(3872)→π0π0χc1,2 normalized to the branching fraction of X(3872)→π+π−J/ψ are set to be B(X(3872)→π0π0χc1)/B(X(3872)→π+π−J/ψ)<1.1 and B(X(3872)→π0π0χc2)/B(X(3872)→π+π−J/ψ)<0.5, taking into account both statistical and systematic uncertainties.
Using e+e− collision data, corresponding to an integrated luminosity of 892pb−1 collected at center-of-mass energies from 4.84 to 4.95\,GeV with the BESIII detector, we search for the process e+e−→K+K−ψ(3770) by reconstructing two charged kaons and one D meson from ψ(3770). No significant signal of e+e−→K+K−ψ(3770) is found and the upper limits of the Born cross sections are reported at 90\% confidence level.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e+e−→η+X, normalized by the total cross section of e+e−→hadrons, is measured at eight center-of-mass energy points from 2.0000 GeV to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy from calculations with the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.
The processes hc→γP(P=η′, η, π0) are studied with a sample of (27.12±0.14)×108 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The decay hc→γη is observed for the first time with the significance of 9.0σ, and the branching fraction is determined to be (3.77±0.55±0.13±0.26)×10−4, while B(hc→γη′) is measured to be (1.40±0.11±0.04±0.10)×10−3, where the first uncertainties are statistical, the second systematic, and the third from the branching fraction of ψ(3686)→π0hc. The combination of these results allows for a precise determination of Rhc=B(hc→γη)B(hc→γη′), which is calculated to be (27.0±4.4±1.0)%. The results are valuable for gaining a deeper understanding of η−η′ mixing, and its manifestation within quantum chromodynamics. No significant signal is found for the decay hc→γπ0, and an upper limit is placed on its branching fraction of B(hc→γπ0)<5.0×10−5, at the 90% confidence level.
Observation of a vector charmoniumlike state at 4.7 GeV/c² and search for Zcₛ in e⁺e⁻ → K⁺K⁻J/ψ
(2023)
Using data samples with an integrated luminosity of 5.85~fb−1 collected at center-of-mass energies from 4.61 to 4.95 GeV with the BESIII detector operating at the BEPCII storage ring, we measure the cross section for the process e+e−→K+K−J/ψ. A new resonance with a mass of M=4708+17−15±21 MeV/c2 and a width of Γ=126+27−23±30 MeV is observed in the energy-dependent line shape of the e+e−→K+K−J/ψ cross section with a significance over 5σ. The K+J/ψ system is also investigated to search for charged charmoniumlike states, but no significant Z+cs states are observed. Upper limits on the Born cross sections for e+e−→K−Zcs(3985)+/K−Zcs(4000)++c.c. with Zcs(3985)±/Zcs(4000)±→K±J/ψ are reported at 90\% confidence levels. The ratio of branching fractions B(Zcs(3985)+→K+J/ψ)B(Zcs(3985) +→ (D¯0D∗+s+D¯∗0D+s)) is measured to be less than 0.03 at 90\% confidence level.
The e+e−→D+sDs1(2536)− and e+e−→D+sD∗s2(2573)− processes are studied using data samples collected with the BESIII detector at center-of-mass energies from 4.530 to 4.946~GeV. The absolute branching fractions of Ds1(2536)−→D¯∗0K− and D∗s2(2573)−→D¯0K− are measured for the first time to be (35.9±4.8±3.5)% and (37.4±3.1±4.6)%, respectively. The measurements are in tension with predictions based on the assumption that the Ds1(2536) and D∗s2(2573) are dominated by a bare cs¯ component. The e+e−→D+sDs1(2536)− and e+e−→D+sD∗s2(2573)− cross sections are measured, and a resonant structure at around 4.6~GeV with a width of 50~MeV is observed for the first time with a statistical significance of 15σ in the e+e−→D+sD∗s2(2573)− process. It could be the Y(4626) found by the Belle collaboration in the D+sDs1(2536)− final state, since they have similar masses and widths. There is also evidence for a structure at around 4.75~GeV in both processes.
In this Letter, a systematic study of the weak radiative hyperon decay Ξ0→Λγ at an electron-positron collider using entangled Ξ0Ξ¯0 pair events is presented. The absolute branching fraction for this decay has been measured for the first time, and is (1.347±0.066stat.±0.054syst.)×10−3. The decay asymmetry parameter, which characterizes the effect of parity violation in the decay, is determined to be −0.741±0.062stat.±0.019syst.. The obtained results are consistent with the world average values within the uncertainties, offering valuable insights into the underlying mechanism governing the weak radiative hyperon decays. The charge conjugation parity (CP) symmetries of branching fraction and decay asymmetry parameter in the decay are also studied. No statistically significant violation of charge conjugation parity symmetry is observed.
In this Letter, a systematic study of the weak radiative hyperon decay Ξ0→Λγ at an electron-positron collider using entangled Ξ0Ξ¯0 pair events is presented. The absolute branching fraction for this decay has been measured for the first time, and is (1.347±0.066stat.±0.054syst.)×10−3. The decay asymmetry parameter, which characterizes the effect of parity violation in the decay, is determined to be −0.741±0.062stat.±0.019syst.. The obtained results are consistent with the world average values within the uncertainties, offering valuable insights into the underlying mechanism governing the weak radiative hyperon decays. The charge conjugation parity (CP) symmetries of branching fraction and decay asymmetry parameter in the decay are also studied. No statistically significant violation of charge conjugation parity symmetry is observed.
Using data samples with an integrated luminosity of 4.67 fb−1 collected by the BESIII detector operating at the BEPCII collider, we search for the process e+e−→η′ψ(2S) at center-of-mass energies from 4.66 to 4.95 GeV. No significant signal is observed, and upper limits for the Born cross sections σB(e+e−→η′ψ(2S)) at the 90\% confidence level are determined.
Using 9.0 fb−1 of e+e− collision data collected at center-of-mass energies from 4.178 to 4.278 GeV with the BESIII detector at the BEPCII collider, we perform the first search for the radiative transition χc1(3872)→γψ2(3823). No χc1(3872)→γψ2(3823) signal is observed. The upper limit on the ratio of branching fractions B(χc1(3872)→γψ2(3823),ψ2(3823)→γχc1)/B(χc1(3872)→π+π−J/ψ) is set as 0.075 at the 90\% confidence level. Our result contradicts theoretical predictions under the assumption that the χc1(3872) is the pure charmonium state χc1(2P).
We report the first amplitude analysis of the decays D0→π+π−η and D+→π+π0η using a data sample taken with the BESIII detector at the center-of-mass energy of 3.773 GeV, corresponding to an integrated luminosity of 7.9 fb−1. The contribution from the process D0(+)→a0(980)+π−(0) is significantly larger than the D0(+)→a0(980)−(0)π+ contribution. The ratios B(D0→a0(980)+π−)/B(D0→a0(980)−π+) and B(D+→a0(980)+π0)/B(D+→a0(980)0π+) are measured to be 7.5+2.5−0.8stat.±1.7syst. and 2.6±0.6stat.±0.3syst., respectively. The measured D0 ratio disagrees with the theoretical predictions by orders of magnitudes, thus implying a substantial contribution from final-state interactions.
The process e+e−→pp¯π0 is studied at 20 center-of-mass energies ranging from 2.1000 to 3.0800 GeV using 636.8 pb−1 of data collected with the BESIII detector operating at the BEPCII collider. The Born cross sections for e+e−→pp¯π0 are measured with high precision. Since the lowest center-of-mass energy, 2.1000 GeV, is less than 90 MeV above the pp¯π0 energy threshold, we can probe the threshold behavior for this reaction. However, no anomalous threshold enhancement is found in the cross sections for e+e−→pp¯π0.
Using 7.33~fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies in the range of s√=4.128−4.226~GeV, we search for the rare decays D+s→h+(h0)e+e−, where h represents a kaon or pion. By requiring the e+e− invariant mass to be consistent with a ϕ(1020), 0.98<M(e+e−)<1.04 ~GeV/c2, the decay D+s→π+ϕ,ϕ→e+e− is observed with a statistical significance of 7.8σ, and evidence for the decay D+s→ρ+ϕ,ϕ→e+e− is found for the first time with a statistical significance of 4.4σ. The decay branching fractions are measured to be B(D+s→π+ϕ,ϕ→e+e−)=(1.17+0.23−0.21±0.03)×10−5, and B(D+s→ρ+ϕ,ϕ→e+e−)=(2.44+0.67−0.62±0.16)×10−5, where the first uncertainties are statistical and the second systematic. No significant signal for the three four-body decays of D+s→π+π0e+e−, D+s→K+π0e+e−, and D+s→K0Sπ+e+e− is observed. For D+s→π+π0e+e−, the ϕ mass region is vetoed to minimize the long-distance effects. The 90% confidence level upper limits set on the branching fractions of these decays are in the range of (7.0−8.1)×10−5.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative decays of the J/ψ, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a narrow resonance and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.6−49.8)×10−8 and (2.2−103.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
Based on (2.712±0.014)×109 ψ(3686) events collected by the BESIII collaboration, evidence of the hadronic decay hc→K0SK+π−+c.c. is found with a significance of 4.3σ in the ψ(3686)→π0hc process. The branching fraction of hc→K0SK+π−+c.c. is measured to be (7.3±0.8±1.8)×10−4, where the first and second uncertainties are statistical and systematic, respectively. Combining with the exclusive decay width of ηc→KK¯π, our result indicates inconsistencies with both pQCD and NRQCD predictions.
Six C-even states, denoted as X, with quantum numbers JPC=0−+, 1±+, or 2±+, are searched for via the e+e−→γD±sD∗∓s process using (1667.39±8.84) pb−1 of e+e− collision data collected with the BESIII detector operating at the BEPCII storage ring at center-of-mass energy of s√=(4681.92±0.30) MeV. No statistically significant signal is observed in the mass range from 4.08 to 4.32 GeV/c2. The upper limits of σ[e+e−→γX]⋅B[X→D±sD∗∓s] at a 90% confidence level are determined.
The processes hc→γP(P=η′, η, π0)) are studied with a sample of (27.12±0.14)×108 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The branching fractions of hc→γη′ and hc→γη are measured to be (1.40±0.11±0.04±0.10)×10−3 and (3.77±0.55±0.13±0.26)×10−4, respectively, where the first uncertainties are statistical, the second systematic, and the third from the branching fraction of ψ(3686)→π0hc. The ratio Rhc=B(hc→γη)B(hc→γη′) is calculated to be (27.0±4.4±1.0)%. The measurements are consistent with the previous results with improved precision by a factor of 2. The results are valuable for gaining a deeper understanding of η−η′ mixing, and its manifestation within quantum chromodynamics. No significant signal is found for the decay hc→γπ0, and an upper limit is placed on its branching fraction of B(hc→γπ0)<5.0×10−5, at the 90\% confidence level.
Based on 4.5 fb−1 of e+e− collision data accumulated at center-of-mass energies between 4599.53 MeV and 4698.82 MeV with the BESIII detector, the decay Λ+c→nK0Sπ+π0 is observed for the first time with a significance of 9.2σ. The branching fraction is measured to be (0.85±0.13±0.03)%, where the first uncertainty is statistical and the second systematic, which differs from the theoretical prediction based on isospin by 4.4σ. This indicates that there may be resonant contributions or some unknown dynamics in this decay.
The process 𝑒+𝑒−→Σ+¯Σ− is studied from threshold up to 3.04 GeV/𝑐2 via the initial-state radiation technique using data with an integrated luminosity of 12.0 fb−1, collected at center-of-mass energies between 3.773 and 4.258 GeV with the BESIII detector at the BEPCII collider. The pair production cross sections and the effective form factors of Σ are measured in eleven Σ+¯Σ− invariant mass intervals from threshold to 3.04 GeV/𝑐2. The results are consistent with the previous results from Belle and BESIII. Furthermore, the branching fractions of the decays 𝐽/𝜓→Σ+¯Σ− and 𝜓(3686)→Σ+¯Σ− are determined and the obtained results are consistent with the previous results of BESIII.
Using (2712.4±14.3)×106 ψ(3686) events collected with the BESIII detector operating at the BEPCII collider, we search for the hadronic transition hc→π+π−J/ψ via ψ(3686)→π0hc. No significant signal is observed. We set the most stringent upper limits to date on the branching fractions B(ψ(3686)→π0hc)×B(hc→π+π−J/ψ) and B(hc→π+π−J/ψ) at the 90% confidence level, which are determined to be 6.7×10−7 and 9.4×10−4, respectively.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative J/ψ decays, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a signal and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.7−48.5)×10−8 and (2.2−101.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
Observation of η_(c)(1S, 2S) and χ_(cJ) decays to 2(π⁺π^(−))η via ψ(3686) radiative transitions
(2024)
Based on 2.7×109 ψ(3686) decays collected with the BESIII detector, the radiative decay ψ(3686)→γ2(π+π−)η is investigated to measure properties of S- and P-wave charmonium states. The branching fraction of the decay ηc(1S)→2(π+π−)η, which is found to have a strong dependence on the interference pattern between ηc(1S) and non-ηc(1S) processes, is measured in both destructive and constructive interference scenarios for the first time. The mass and width of the ηc(1S) are measured to be M=(2984.14±0.13±0.38) MeV/c2 and Γ=(28.82±0.11±0.82) MeV, respectively. Clear signals for the decays of the χcJ(J=0,1,2) and the ηc(2S) to 2(π+π−)η are also observed for the first time, and the corresponding branching fractions are measured. The ratio of the branching fractions between the ηc(2S) and ηc(1S) decays is significantly lower than the theoretical prediction, which might suggest different dynamics in their decays.
Based on (2712.4±14.3)×106 ψ(3686) events, we investigate four hadronic decay modes of the P-wave charmonium spin-singlet state hc(1P1)→h+h−π0/η (h=π or K) via the process ψ(3686)→π0hc at BESIII. The hc→π+π−π0 decay is observed with a significance of 9.6σ after taking into account systematic uncertainties. Evidences for hc→K+K−π0 and hc→K+K−η are found with significances of 3.5σ and 3.3σ, respectively, after considering the systematic uncertainties. The branching fractions of these decays are measured to be B(hc→π+π−π0)=(1.36±0.16±0.14)×10−3, B(hc→K+K−π0)=(3.26±0.84±0.36)×10−4, and B(hc→K+K−η)=(3.13±1.08±0.38)×10−4, where the first uncertainties are statistical and the second are systematic. No significant signal of hc→π+π−η is found, and the upper limit of its decay branching fraction is determined to be B(hc→π+π−η)<4.0×10−4 at 90% confidence level.
Using 7.93 fb−1 of e+e− collision data collected at the center-of-mass energy of 3.773 GeV with the BESIII detector, we measure the absolute branching fractions of D0→K−e+νe, D0→K−μ+νμ, D+→K¯0e+νe, and D+→K¯0μ+νμ to be (3.509±0.009stat.±0.013syst.)%, (3.408±0.011stat.±0.013syst.)%, (8.856±0.039stat.±0.078syst.)%, and (8.661±0.046stat.±0.080syst.)%, respectively. By performing a simultaneous fit to the partial decay rates of these four decays, the product of the hadronic form factor fK+(0) and the modulus of the c→s CKM matrix element |Vcs| is determined to be fK+(0)|Vcs|=0.7162±0.0011stat.±0.0012syst.. Taking the value of |Vcs|=0.97349±0.00016 from the standard model global fit or that of fK+(0)=0.7452±0.0031 from the LQCD calculation as input, we derive the results fK+(0)=0.7357±0.0011stat.±0.0012syst. and |Vcs|=0.9611±0.0015stat.±0.0016syst.±0.0040LQCD.
We measure the Born cross section for the reaction e+e−→ηhc from s√=4.129 to 4.600~GeV using data sets collected by the BESIII detector running at the BEPCII collider. A resonant structure in the cross section line shape near 4.200~GeV is observed with a statistical significance of 7σ. The parameters of this resonance are measured to be \MeasMass\ and \MeasWidth, where the first uncertainties are statistical and the second systematic.
Background: Obesity and depression are both associated with changes in sleep/wake regulation, with potential implications for individualized treatment especially in comorbid individuals suffering from both. However, the associations between obesity, depression, and subjective, questionnaire-based and objective, EEG-based measurements of sleepiness used to assess disturbed sleep/wake regulation in clinical practice are not well known.
Objectives: The study investigates associations between sleep/wake regulation measures based on self-reported subjective questionnaires and EEG-derived measurements of sleep/wake regulation patterns with depression and obesity and how/whether depression and/or obesity affect associations between such self-reported subjective questionnaires and EEG-derived measurements.
Methods: Healthy controls (HC, NHC = 66), normal-weighted depressed (DEP, NDEP = 16), non-depressed obese (OB, NOB = 68), and obese depressed patients (OBDEP, NOBDEP = 43) were included from the OBDEP (Obesity and Depression, University Leipzig, Germany) study. All subjects completed standardized questionnaires related to daytime sleepiness (ESS), sleep quality and sleep duration once as well as questionnaires related to situational sleepiness (KSS, SSS, VAS) before and after a 20 min resting state EEG in eyes-closed condition. EEG-based measurements of objective sleepiness were extracted by the VIGALL algorithm. Associations of subjective sleepiness with objective sleepiness and moderating effects of obesity, depression, and additional confounders were investigated by correlation analyses and regression analyses.
Results: Depressed and non-depressed subgroups differed significantly in most subjective sleepiness measures, while obese and non-obese subgroups only differed significantly in few. Objective sleepiness measures did not differ significantly between the subgroups. Moderating effects of obesity and/or depression on the associations between subjective and objective measures of sleepiness were rarely significant, but associations between subjective and objective measures of sleepiness in the depressed subgroup were systematically weaker when patients comorbidly suffered from obesity than when they did not.
Conclusion: This study provides some evidence that both depression and obesity can affect the association between objective and subjective sleepiness. If confirmed, this insight may have implications for individualized diagnosis and treatment approaches in comorbid depression and obesity.
Treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute leukemia (Ph+ ALL) has been revolutionized with the advent of tyrosine kinase inhibitors (TKIs). Most patients with CML achieve long-term survival similar to individuals without CML due to treatment with TKIs not only in frontline but also in further lines of therapy. The third-generation TKI ponatinib has demonstrated efficacy in patients with refractory CML and Ph+ ALL. Ponatinib is currently the most potent TKI in this setting demonstrating activity against T315I mutant clones. However, ponatinib’s safety data revealed a dose-dependent, increased risk of serious cardiovascular (CV) events. Guidance is needed to evaluate the benefit–risk profile of TKIs, such as ponatinib, and safety measures to prevent treatment-associated CV events. An expert panel of German hematologists and cardiologists summarize current evidence regarding ponatinib’s efficacy and CV safety profile. We propose CV management strategies for patients who are candidates for ponatinib.
The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). Seventy seven (77) cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Systematic protein localization and protein-protein interaction studies to characterize specific protein functions are most effectively performed using tag-based assays. Ideally, protein tags are introduced into a gene of interest by homologous recombination to ensure expression from endogenous control elements. However, inefficient homologous recombination makes this approach difficult in mammalian cells. Although gene targeting efficiency by homologous recombination increased dramatically with the development of designer endonuclease systems such as CRISPR/Cas9 capable of inducing DNA double-strand breaks with unprecedented accuracy, the strategies still require synthesis or cloning of homology templates for every single gene. Recent developments have shown that endogenous protein tagging can be achieved efficiently in a homology independent manner. Hence, combinations between CRISPR/Cas9 and generic tag-donor plasmids have been used successfully for targeted gene modifications in mammalian cells. Here, we developed a tool kit comprising a CRISPR/Cas9 expression vector with several EGFP encoding plasmids that should enable tagging of almost every protein expressed in mammalian cells. By performing protein-protein interaction and subcellular localization studies of mTORC1 signal transduction pathway-related proteins expressed in HEK293T cells, we show that tagged proteins faithfully reflect the behavior of their native counterparts under physiological conditions.
In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.
Chondrules are thought to play a crucial role in planet formation, but the mechanisms leading to their formation are still a matter of unresolved discussion. So far, experiments designed to understand chondrule formation conditions have been carried out only under the influence of terrestrial gravity. In order to introduce more realistic conditions, we developed a chondrule formation experiment, which was carried out at long-term microgravity aboard the International Space Station. In this experiment, freely levitating forsterite (Mg2SiO4) dust particles were exposed to electric arc discharges, thus simulating chondrule formation via nebular lightning. The arc discharges were able to melt single dust particles completely, which then crystallized with very high cooling rates of >105 K h−1. The crystals in the spherules show a crystallographic preferred orientation of the [010] axes perpendicular to the spherule surface, similar to the preferred orientation observed in some natural chondrules. This microstructure is probably the result of crystallization under microgravity conditions. Furthermore, the spherules interacted with the surrounding gas during crystallization. We show that this type of experiment is able to form spherules, which show some similarities with the morphology of chondrules despite very short heating pulses and high cooling rates.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis
(2020)
Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
We performed an experiment under long-term microgravity conditions aboard the International Space Station (ISS) to obtain information on the energetics and experimental constraints required for the formation of chondrules in the solar nebula by ’nebular lightning’. As a simplified model system, we exposed porous forsterite (Mg2 SiO4) dust particles to high-energetic arc discharges. The characterization of the samples after their return by synchrotron microtomography and scanning electron microscopy revealed that aggregates had formed, consisting of several fused Mg2SiO4 particles. The partial melting and fusing of Mg2SiO4 dust particles under microgravity conditions leads to a strong reduction of their porosity. The experimental outcomes vary strongly in their appearance from small spherical melt-droplets (∅≈90 µm) to bigger and irregularly shaped aggregates (∅≈350 µm). Our results provided new constraints with respect to energetic aspects of chondrule formation and a roadmap for future and more complex experiments on Earth and in microgravity conditions.
Eisnukleierende Partikel (INP) sind ein wichtiger Bestandteil des atmosphärischen Aerosols. Trotz ihrer geringen Konzentrationen in der Atmosphäre haben sie Einfluss auf die Bildung von Eiskristallen und auf den Niederschlag. Durch Änderungen in Anzahlkonzentration oder anderer Eigenschaften der INP können sich Wolkenparameter wie Lebensdauer und Tröpfchendichte ändern, was weiter eine Ursache für Änderungen im globalen Strahlungshaushalt sein kann.
Der Anteil zum globalen Strahlungshaushalt durch „Wolken-Anpassungen aufgrund von Aerosolen“, stellt weiterhin die größte Unsicherheit des Strahlungsantriebes dar. Aus diesem Grund sind Messungen und Studien über atmosphärische Aerosole und INP notwendig. Im Rahmen dieser Arbeit wurde der Eiskeimzähler FINCH („fast ice nucleus chamber“) grundlegend überholt und für Messungen von INP optimiert. FINCH ist ein in-situ Eiskeimzähler der durch Mischung unterschiedlicher Luftströme eine Übersättigung der Probeluft mit Wasserdampf erzeugt, um auf diese Weise die zu untersuchenden Aerosolpartikel zu Eiskristallen wachsen zu lassen. Am Ende einer Wachstumskammer werden die Partikel durch eine Optik, dem FINCH-OPS, anhand von Streueigenschaften klassifiziert und ausgewertet. Um FINCH im erwarteten Umfang benutzen zu können, wurden am F-OPS der Laser und die zur Detektion des Streulichts benutzen Photomultiplier ersetzt. Weiter wurde die Software zur Detektion der Partikel neu entwickelt. Durch diese Änderungen ist es möglich Partikelanzahl, Partikelgröße sowie eine Information über die Form der Partikel abzuleiten. Über einen weiteren Photomultiplier im F-OPS ist es zudem möglich eine Information über Fluoreszenz des Partikels zu gewinnen, um so auf einen biologischen Ursprung des Partikels zu schließen. Vorangegangene Probleme durch elektromagnetische Einstrahlung und dadurch entstandene Inkonsistenzen während Messungen konnten im Rahmen dieser Arbeit identifiziert und ausgeschlossen werden. Ebenfalls konnten die zur Flusskühlung benutzen Wärmetaucher als Ursache für Verunreinigungen und Kontamination ausgemacht werden. Auch dieser, für Messungen ungeeignete Zustand, wurde im Rahmen dieser Arbeit behoben.
Ausführliche Charakterisierungsmessungen konnte die Funktionsfähigkeit des F-OPS, als einzelnes Messgerät ohne FINCH-Kammer, belegen. Durch Messungen mit einer steuerbaren Lichtquelle in der Optik konnte zudem die elektrische Verarbeitung sowie die Zählqualität der Optik verifiziert werden. Weiter kann durch diese Experimente gezeigt werden, dass mit dem F-OPS größenaufgelöst gemessen werden kann.
Auch in den ersten Streulichtexperimenten mit Testaerosol kann die Funktionsfähigkeit der Optik gezeigt werden. Für Partikelgröße von Dp > 400 nm wird eine Zähleffizienz von 25% eines TSI 3025 CPCs erreicht. Die über den F-OPS abgeleitete Partikelgröße kann durch Messungen mit monodispersen Aerosolpartikeln und einer parallelen Messung mit einem TSI 3330 OPS parametrisiert werden. Weiter kann die Fluoreszenz von ausgewählten Referenzstoffen gezeigt werden.
Im Betrieb von F-OPS hinter der FINCH-Kammer, also FINCH als Komplettsystem, wurden weitere Charakterisierungsmessungen durchgeführt. Es wurde festgestellt, dass die Anzahlkonzentration der Partikel nach Schließen eines Ventils exponentiell abfällt. Die Partikel folgen demnach nicht nur einem laminaren Fluss durch die Kammer. 50% der Partikel haben nach ca. 13 s die Kammer verlassen. Auch wurde ermittelt, dass ca. 40% der Partikel in der Kammer verloren gehen.
Erste Aktivierungsexperimente zeigen, dass Eispartikel in der Kammer auf eine Größe von Dp > 6 µm anwachsen. Durch Nullfiltermessungen in Aktivierungsphasen, sowie Ändern des zur Aktivierung notwendigen feuchten Flusses, wird zudem gezeigt, dass die Aktivierung der INP durch Mischung erfolgt und außerdem keine Fremdpartikel aktiviert werden. Die neue Steuerung der Kammer lässt es zu Temperaturen in etwa einer Stunde gezielt anzusteuern. Es wird gezeigt, dass Schwankungen in der Sättigung hauptsächlich durch Temperaturphänomene beeinflusst werden.
Abschließend wurden beispielhaft Laborexperimente mit Snomax© durchgeführt, welche sehr gut mit Werten aus der Literatur verglichen werden konnten. Auch eine erste Außenluftmessung am Jungfraujoch (Schweiz) wird in dieser Arbeit präsentiert. Die gemessenen INP-Konzentrationen im gezeigten Zeitraum liegen zwischen 1,4 ± 4,1 L-1 und 53 ± 30 L-1 und entsprechen somit wiederum bekannten Literaturwerten.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice-nucleating particles. However, an intercomparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nuclei Research Unit), we distributed an illite-rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. A total of 17 measurement methods were involved in the data intercomparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while 10 other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing data set was evaluated using the ice nucleation active surface-site density, ns, to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers 9 orders of magnitude in ns.
In general, the 17 immersion freezing measurement techniques deviate, within a range of about 8 °C in terms of temperature, by 3 orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency expressed in ns of illite NX particles is relatively independent of droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature dependence and weak time and size dependence of the immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns(T) spectra and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. While the agreement between different instruments was reasonable below ~ −27 °C, there seemed to be a different trend in the temperature-dependent ice nucleation activity from the suspension and dry-dispersed particle measurements for this mineral dust, in particular at higher temperatures. For instance, the ice nucleation activity expressed in ns was smaller for the average of the wet suspended samples and higher for the average of the dry-dispersed aerosol samples between about −27 and −18 °C. Only instruments making measurements with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −27 and −18 °C is discussed. Multiple exponential distribution fits in both linear and log space for both specific surface area-based ns(T) and geometric surface area-based ns(T) are provided. These new fits, constrained by using identical reference samples, will help to compare IN measurement methods that are not included in the present study and IN data from future IN instruments.
CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Post‐traumatic stress disorder (PTSD) is associated with a hypersensitivity to potential threat. This hypersensitivity manifests through differential patterns of emotional information processing and has been demonstrated in behavioral and neurophysiological experimental paradigms. However, the majority of research has been focused on adult patients with PTSD. To examine possible differences in underlying neurophysiological patterns for adolescent patients with PTSD after childhood sexual and/or physical abuse (CSA/CPA), ERP correlates of emotional word processing in 38 healthy participants and 40 adolescent participants with PTSD after experiencing CSA/CPA were studied. The experimental paradigm consisted of a passive reading task with neutral, positive (e.g., paradise), physically threatening (e.g., torment), and socially threatening (i.e., swearing, e.g., son of a bitch) words. A modulation of P3 amplitudes by emotional valence was found, with positive words inducing less elevated amplitudes over both groups. Interestingly, in later processing, the PTSD group showed augmented early late positive potential (LPP) amplitudes for socially threatening stimuli, while there were no modulations within the healthy control group. Also, region‐specific emotional modulations for anterior and posterior electrode clusters were found. For the anterior LPP, highest activations have been found for positive words, while socially and physically threatening words led to strongest modulations in the posterior LPP cluster. There were no modulations by group or emotional valence at the P1 and EPN stage. The findings suggest an enhanced conscious processing of socially threatening words in adolescent patients with PTSD after CSA/CPA, pointing to the importance of a disjoined examination of threat words in emotional processing research.
Cardiac reactions to emotional words in adolescents and young adults with PTSD after child abuse
(2019)
Post‐traumatic stress disorder (PTSD) is associated with alterations in cardiac reactivity to threat cues. Meta‐analyses have summarized that adults with PTSD have increased heart rates in response to trauma‐related stimuli. However, the opposite effect (i.e., cardiac hyporeactivity) has recently been reported in subgroups of PTSD patients. In children and adolescents with PTSD, reports of cardiac alterations are rare and ambiguous. So far, most studies in adolescents and young adults are restricted to victims of accidents, even though PTSD is highly prevalent in victims of child maltreatment. The present study aimed at investigating cardiac reactions in adolescents and young adults with PTSD after child abuse. Cardiac responses to standardized emotional words were studied in 39 adolescent and young adult PTSD patients after childhood sexual and/or physical abuse as compared to 39 healthy control subjects (age range: 15–20 years). The experimental paradigm consisted of a passive reading task with neutral, positive, physically threatening, and socially threatening (swear) words. Results showed that cardiac reactions to negative stimuli, particularly physically threatening stimuli, were less pronounced in PTSD patients than in controls. Moreover, cardiac reactions in response to socially threatening words were less variable in the PTSD group. No differences between and within groups were present in reaction to neutral or positive stimuli. Findings suggest that a physiologically blunted subtype of PTSD may already manifest during adolescence and young adulthood. Moreover, the results of the present study emphasize the relevance of individual trauma history for physiological reactions.
Treatment‐related complications contribute substantially to morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Although AML patients are susceptible to fluid overload (FO) (e.g., in the context of chemotherapy protocols, during sepsis treatment or to prevent tumor lysis syndrome), little attention has been paid to its role in AML patients undergoing induction chemotherapy. AML patients receiving induction chemotherapy between 2014 and 2019 were included in this study. FO was defined as ≥5% weight gain on day 7 of induction chemotherapy compared to baseline weight determined on the day of admission. We found FO in 23 (12%) of 187 AML patients undergoing induction chemotherapy. Application of >100 ml crystalloid fluids/kg body weight until day 7 of induction chemotherapy was identified as an independent risk factor for FO. AML patients with FO suffered from a significantly increased 90-day mortality rate and FO was demonstrated as an independent risk factor for 90-day mortality. Our data suggests an individualized, weight-adjusted calculation of crystalloid fluids in order to prevent FO-related morbidity and mortality in AML patients during induction chemotherapy. Prospective trials are required to determine the adequate fluid management in this patient population.
Simple Summary: In patients with myeloproliferative neoplasms (MPN) and in patients with kidney dysfunction, a higher rate of thrombosis has been reported compared with the general population. Furthermore, MPN patients are more prone to develop kidney dysfunction. In our study, we assessed the importance of specific risk factors for kidney dysfunction and thrombosis in MPN patients. We found that the rate of thrombosis is correlated with the degree of kidney dysfunction, especially in myelofibrosis. Significant associations for kidney dysfunction included arterial hypertension, MPN treatment, and increased inflammation, and those for thrombosis comprised arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The identified risk factor associations varied between MPN subtypes. Our data suggest that kidney dysfunction in MPN patients is associated with an increased risk of thrombosis, mandating closer monitoring, and, possibly, early thromboprophylaxis.
Abstract: Inflammation-induced thrombosis represents a severe complication in patients with myeloproliferative neoplasms (MPN) and in those with kidney dysfunction. Overlapping disease-specific attributes suggest common mechanisms involved in MPN pathogenesis, kidney dysfunction, and thrombosis. Data from 1420 patients with essential thrombocythemia (ET, 33.7%), polycythemia vera (PV, 38.5%), and myelofibrosis (MF, 27.9%) were extracted from the bioregistry of the German Study Group for MPN. The total cohort was subdivided according to the calculated estimated glomerular filtration rate (eGFR, (mL/min/1.73 m2)) into eGFR1 (≥90, 21%), eGFR2 (60–89, 56%), and eGFR3 (<60, 22%). A total of 29% of the patients had a history of thrombosis. A higher rate of thrombosis and longer MPN duration was observed in eGFR3 than in eGFR2 and eGFR1. Kidney dysfunction occurred earlier in ET than in PV or MF. Multiple logistic regression analysis identified arterial hypertension, MPN treatment, increased uric acid, and lactate dehydrogenase levels as risk factors for kidney dysfunction in MPN patients. Risk factors for thrombosis included arterial hypertension, non-excessive platelet counts, and antithrombotic therapy. The risk factors for kidney dysfunction and thrombosis varied between MPN subtypes. Physicians should be aware of the increased risk for kidney disease in MPN patients, which warrants closer monitoring and, possibly, early thromboprophylaxis.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice nucleating particles (INPs). However, an inter-comparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nucleation research UnIT), we distributed an illite rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. Seventeen measurement methods were involved in the data inter-comparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while ten other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing dataset was evaluated using the ice nucleation active surface-site density (ns) to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers nine orders of magnitude in ns.
Our inter-comparison results revealed a discrepancy between suspension and dry-dispersed particle measurements for this mineral dust. While the agreement was good below ~ −26 °C, the ice nucleation activity, expressed in ns, was smaller for the wet suspended samples and higher for the dry-dispersed aerosol samples between about −26 and −18 °C. Only instruments making measurement techniques with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −26 and −18 °C is discussed. In general, the seventeen immersion freezing measurement techniques deviate, within the range of about 7 °C in terms of temperature, by three orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency (i.e., ns) of illite NX particles is relatively independent on droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature-dependence and weak time- and size-dependence of immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns (T) spectra, and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. A multiple exponential distribution fit is expressed as ns(T) = exp(23.82 × exp(−exp(0.16 × (T + 17.49))) + 1.39) based on the specific surface area and ns(T) = exp(25.75 × exp(−exp(0.13 × (T + 17.17))) + 3.34) based on the geometric area (ns and T in m−2 and °C, respectively). These new fits, constrained by using an identical reference samples, will help to compare IN measurement methods that are not included in the present study and, thereby, IN data from future IN instruments.
In the present work, three different techniques are used to separate ice-nucleating particles (INP) and ice particle residuals (IPR) from non-ice-active particles: the Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI), which sample ice particles from mixed phase clouds and allow for the analysis of the residuals, as well as the combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Virtual Impactor (IN-PCVI), which provides ice-activating conditions to aerosol particles and extracts the activated ones for analysis. The collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine their size, chemical composition and mixing state. Samples were taken during January/February 2013 at the High Alpine Research Station Jungfraujoch. All INP/IPR-separating techniques had considerable abundances (median 20–70%) of contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH + IN-PCVI: steel particles). Also, potential measurement artifacts (soluble material) occurred (median abundance < 20%). After removal of the contamination particles, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Minor types include soot and Pb-bearing particles. Sea-salt and sulfates were identified by all three methods as INP/IPR. Lead was identified in less than 10% of the INP/IPR. It was mainly present as an internal mixture with other particle types, but also external lead-rich particles were found. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also sampled many submicron particles. Probably owing to the different meteorological conditions, the INP/IPR composition was highly variable on a sample to sample basis. Thus, some part of the discrepancies between the different techniques may result from the (unavoidable) non-parallel sampling. The observed differences of the particles group abundances as well as the mixing state of INP/IPR point to the need of further studies to better understand the influence of the separating techniques on the INP/IPR chemical composition.
During January/February 2013, at the High Alpine Research Station Jungfraujoch a measurement campaign was carried out, which was centered on atmospheric ice-nucleating particles (INP) and ice particle residuals (IPR). Three different techniques for separation of INP and IPR from the non-ice-active particles are compared. The Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI) sample ice particles from mixed phase clouds and allow for the analysis of the residuals. The combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Counterflow Virtual Impactor (IN-PCVI) provides ice-activating conditions to aerosol particles and extracts the activated INP for analysis.Collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine size, chemical composition and mixing state. All INP/IPR-separating techniques had considerable abundances (median 20 – 70 %) of instrumental contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH+IN-PCVI: steel particles). Also, potential sampling artifacts (e.g., pure soluble material) occurred with a median abundance of < 20 %. While these could be explained as IPR by ice break-up, for INP their IN-ability pathway is less clear. After removal of the contamination artifacts, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Soot was a minor contributor. Lead was detected in less than 10 % of the particles, of which the majority were internal mixtures with other particle types. Sea-salt and sulfates were identified by all three methods as INP/IPR. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also separated many submicron IPR. As strictly parallel sampling could not be performed, a part of the discrepancies between the different techniques may result from variations in meteorological conditions and subsequent INP/IPR composition. The observed differences in the particle group abundances as well as in the mixing state of INP/IPR express the need for further studies to better understand the influence of the separating techniques on the INP/IPR chemical
composition.
The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
In order to gain further insights into early solar system aggregation processes, we carried out an experiment on board the International Space Station, which allowed us to study the behavior of dust particles exposed to electric arc discharges under long-term microgravity. The experiment led to the formation of robust, elongated, fluffy aggregates, which were studied by scanning electron microscopy, electron backscatter diffraction, and synchrotron micro-computed tomography. The morphologies of these aggregates strongly resemble the typical shapes of fractal fluffy-type calcium-aluminum-rich inclusions (CAIs). We conclude that a small amount of melting could have supplied the required stability for such fractal structures to have survived transportation and aggregation to and compaction within planetesimals. Other aggregates produced in our experiment have a massy morphology and contain relict grains, likely resulting from the collision of grains with different degrees of melting, also observed in some natural CAIs. Some particles are surrounded by igneous rims, which remind in thickness and crystal orientation of Wark–Lovering rims; another aggregate shows similarities to disk-shaped CAIs. These results imply that a (flash-)heating event with subsequent aggregation could have been involved in the formation of different morphological CAI characteristics.
Growing up in cities is associated with increased risk for developing mental health problems. Stress exposure and altered stress regulation have been proposed as mechanisms linking urbanicity and psychopathology, with most research conducted in adult populations. Here, we focus on early childhood, and investigate urbanicity, behavior problems and the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, a central circuit of the stress system, in a sample of N = 399 preschoolers aged 45 months. Urbanicity was coded dichotomously distinguishing between residences with more or less than 100,000 inhabitants. Behavior problems were measured using the Child Behavior Checklist (CBCL) 1½ - 5. Cortisol stress reactivity was assessed using an age-appropriated game-like stress task, and cortisol in the first morning urine was measured to assess nocturnal HPA axis activity. Urbanicity was not associated with behavior problems, urinary cortisol or the cortisol stress response. Neither urinary cortisol nor salivary cortisol response after stress exposure were identified as mediators of the relationship between urbanicity and behavior problems. The findings suggest no strong association of urbanicity with behavior problems and HPA axis regulation in preschool age. To our knowledge, this is the youngest sample to date studying the relationship between urbanicity and behavior problems as well as HPA axis regulation. Future research should examine at which age associations can first be identified and which mechanisms contribute to these relationships.
The survivin suppressant YM155 is a drug candidate for neuroblastoma. Here, we tested YM155 in 101 neuroblastoma cell lines (19 parental cell lines, 82 drug-adapted sublines). 77 cell lines displayed YM155 IC50s in the range of clinical YM155 concentrations. ABCB1 was an important determinant of YM155 resistance. The activity of the ABCB1 inhibitor zosuquidar ranged from being similar to that of the structurally different ABCB1 inhibitor verapamil to being 65-fold higher. ABCB1 sequence variations may be responsible for this, suggesting that the design of variant-specific ABCB1 inhibitors may be possible. Further, we showed that ABCC1 confers YM155 resistance. Previously, p53 depletion had resulted in decreased YM155 sensitivity. However, TP53-mutant cells were not generally less sensitive to YM155 than TP53 wild-type cells in this study. Finally, YM155 cross-resistance profiles differed between cells adapted to drugs as similar as cisplatin and carboplatin. In conclusion, the large cell line panel was necessary to reveal an unanticipated complexity of the YM155 response in neuroblastoma cell lines with acquired drug resistance. Novel findings include that ABCC1 mediates YM155 resistance and that YM155 cross-resistance profiles differ between cell lines adapted to drugs as similar as cisplatin and carboplatin.
Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ~2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the Xchromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87×10-9; odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53×10-9; odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families as well as 438 subjects from an independent, sporadic BD case-control cohort were analysed. Polygenic risk scores (PRS) for BD, schizophrenia, and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had significantly higher PRS for all three psychiatric disorders than the independent controls, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and sporadic BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses, therefore, demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. The PRS explained only part of the observed phenotypic variance and rare variants might have also contributed to disease development.
Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
Objective: Skin and soft tissue infections (SSTI) are a commonly known entity of diseases associated with difficult treatment procedures. The current gold standard when there is a rapidly progressing infection of soft tissues with a risk of sepsis is radical surgical debridement accompanied by systemic antibiotic therapy. In clinical settings, local antibiotics alone or formulated within carrier material are commonly used alongside this therapy regimen. One possibility of local antibiotic application is the fixation of colistin with fibrin glue spray. It is not yet sufficiently researched how the local antibiotic concentrations remain as high as possible over time.
Methods: We conducted an animal study including 29 male Wistar rats inducing sterile back sores reaching the muscle fascia. We sprayed only colistin, simultaneously or consecutively, with fibrin glue in different groups in order to measure the tissue concentration of the antibiotic applied locally.
Results: After liquid chromatography and quadrupole mass spectrometry analysis, it could be demonstrated that in comparison to the colistin group, tissue concentrations of colistin stayed significantly higher in the wound tissue when it was fixed with fibrin glue. This was observed in both groups, the simultaneous as well as in the consecutively fibrin glue sprayed groups after colistin application.
Conclusion: The fixation of colistin with the fibrin-glue-spray technique as a carrier for local antibiotic therapy is an easy and inexpensive method and shows promising potential for the treatment of SSTI.
DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.