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BRAF V600E mutations occur frequently in malignant melanoma, but are rare in most malignant glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) and epitheloid glioblastoma (50%) regularly exhibit BRAF mutations. In the present study, we report on three patients with recurrent malignant gliomas harbouring a BRAF V600E mutation. All patients presented with markedly disseminated leptomeningeal disease at recurrence and had progressed after radiotherapy and alkylating chemotherapy. Therefore, estimated life expectancy at recurrence was a few weeks. All three patients received dabrafenib as a single agent and all showed a complete or nearly complete response. Treatment is ongoing and patients are stable for 27 months, 7 months and 3 months, respectively. One patient showed a dramatic radiologic and clinical response after one week of treatment. We were able to generate an ex vivo tumor cell culture from CSF in one patient. Treatment of this cell culture with dabrafenib resulted in reduced cell density and inhibition of ERK phosphorylation in vitro. To date, this is the first series on adult patients with BRAF-mutated malignant glioma and leptomeningeal dissemination treated with dabrafenib monotherapy. All patients showed a dramatic response with one patient showing an ongoing response for more than two years.
Highlights
• PUR, PVC and PLA microplastics affect life-history parameters of Daphnia magna.
• Natural kaolin particles are less toxic than microplastics.
• Microplastic toxicity is material-specific, e.g. PVC is most toxic on reproduction.
• In case of PVC, plastic chemicals are the main driver of microplastic toxicity.
• PLA bioplastics are similarly toxic as conventional plastics.
Abstract
Given the ubiquitous presence of microplastics in aquatic environments, an evaluation of their toxicity is essential. Microplastics are a heterogeneous set of materials that differ not only in particle properties, like size and shape, but also in chemical composition, including polymers, additives and side products. Thus far, it remains unknown whether the plastic chemicals or the particle itself are the driving factor for microplastic toxicity. To address this question, we exposed Daphnia magna for 21 days to irregular polyvinyl chloride (PVC), polyurethane (PUR) and polylactic acid (PLA) microplastics as well as to natural kaolin particles in high concentrations (10, 50, 100, 500 mg/L, ≤ 59 μm) and different exposure scenarios, including microplastics and microplastics without extractable chemicals as well as the extracted and migrating chemicals alone. All three microplastic types negatively affected the life-history of D. magna. However, this toxicity depended on the endpoint and the material. While PVC had the largest effect on reproduction, PLA reduced survival most effectively. The latter indicates that bio-based and biodegradable plastics can be as toxic as their conventional counterparts. The natural particle kaolin was less toxic than microplastics when comparing numerical concentrations. Importantly, the contribution of plastic chemicals to the toxicity was also plastic type-specific. While we can attribute effects of PVC to the chemicals used in the material, effects of PUR and PLA plastics were induced by the mere particle. Our study demonstrates that plastic chemicals can drive microplastic toxicity. This highlights the importance of considering the individual chemical composition of plastics when assessing their environmental risks. Our results suggest that less studied polymer types, like PVC and PUR, as well as bioplastics are of particular toxicological relevance and should get a higher priority in ecotoxicological studies.
The production of Σ0 baryons in the nuclear reaction p (3.5 GeV) + Nb (corresponding to sNN=3.18 GeV) is studied with the detector set-up HADES at GSI, Darmstadt. Σ0s were identified via the decay Σ0→Λγ with subsequent decays Λ→pπ− in coincidence with a e+e− pair from either external (γ→e+e−) or internal (Dalitz decay γ⁎→e+e−) gamma conversions. The differential Σ0 cross section integrated over the detector acceptance, i.e. the rapidity interval 0.5<y<1.1, has been extracted as ΔσΣ0=2.3±(0.2)stat±(−0.6+0.6)sys±(0.2)norm mb, yielding the inclusive production cross section in full phase space σΣ0total=5.8±(0.5)stat±(−1.4+1.4)sys±(0.6)norm±(1.7)extrapol mb by averaging over different extrapolation methods. The Λall/Σ0 ratio within the HADES acceptance is equal to 2.3±(0.2)stat±(−0.6+0.6)sys. The obtained rapidity and momentum distributions are compared to transport model calculations. The Σ0 yield agrees with the statistical model of particle production in nuclear reactions. Keywords: Hyperons, Strangeness, Proton, Nucleus.
Nanoplastics affect the inflammatory cytokine release by primary human monocytes and dendritic cells
(2022)
So far, the human health impacts of nano- and microplastics are poorly understood. Thus, we investigated whether nanoplastics exposure induces inflammatory processes in primary human monocytes and monocyte-derived dendritic cells. We exposed these cells in vitro to nanoplastics of different shapes (irregular vs. spherical), sizes (50–310 nm and polydisperse mixtures) and polymer types (polystyrene; polymethyl methacrylate; polyvinyl chloride, PVC) using concentrations of 30–300 particles cell−1. Our results show that irregular PVC particles induce the strongest cytokine release of these nanoplastics. Irregular polystyrene triggered a significantly higher pro-inflammatory response compared to spherical nanoplastics. The contribution of chemicals leaching from the particles was minor. The effects were concentration-dependent but varied markedly between cell donors. We conclude that nanoplastics exposure can provoke human immune cells to secrete cytokines as key initiators of inflammation. This response is specific to certain polymers (PVC) and particle shapes (fragments). Accordingly, nanoplastics cannot be considered one homogenous entity when assessing their health implications and the use of spherical polystyrene nanoplastics may underestimate their inflammatory effects.
We present first results of a recently started lattice QCD investigation of antiheavy-antiheavy-light-light tetraquark systems including scattering interpolating operators in correlation functions both at the source and at the sink. In particular, we discuss the importance of such scattering interpolating operators for a precise computation of the low-lying energy levels. We focus on the b¯b¯ud four-quark system with quantum numbers I(JP)=0(1+), which has a ground state below the lowest meson-meson threshold. We carry out a scattering analysis using Lüscher's method to extrapolate the binding energy of the corresponding QCD-stable tetraquark to infinite spatial volume. Our calculation uses clover u, d valence quarks and NRQCD b valence quarks on gauge-link ensembles with HISQ sea quarks that were generated by the MILC collaboration.
We present our recent results on antiheavy-antiheavy-light-light tetraquark systems using lattice QCD. Our study of the b¯b¯us four-quark system with quantum numbers JP=1+ and the b¯c¯ud four-quark systems with I(JP)=0(0+) and I(JP)=0(1+) utilizes scattering operators at the sink to improve the extraction of the low-lying energy levels. We found a bound state for b¯b¯us with Ebind,b¯b¯us=(−86±22±10)MeV, but no indication for a bound state in both b¯c¯ud channels. Moreover, we show preliminary results for b¯b¯ud with I(JP)=0(1+), where we used scattering operators both at the sink and the source. We found a bound state and determined its infinite-volume binding energy with a scattering analysis, resulting in Ebind,b¯b¯ud=(−103±8)MeV.
Non-standard errors
(2021)
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
We study tetraquark resonances with lattice QCD potentials computed for two static quarks and two dynamical quarks, the Born-Oppenheimer approximation and the emergent wave method of scattering theory. As a proof of concept we focus on systems with isospin I = 0, but consider different relative angular momenta l of the heavy b quarks. We compute the phase shifts and search for S and T matrix poles in the second Riemann sheet. We predict a new tetraquark resonance for l = 1, decaying into two B mesons, with quantum numbers I(JP) = 0(1−), mass MeV and decay width MeV.
Lattice QCD investigation of a doubly-bottom b̄b̄ud tetraquark with quantum numbers I(JP) = 0(1⁺)
(2019)
We use lattice QCD to investigate the spectrum of the ¯𝑏¯𝑏𝑢𝑑 four-quark system with quantum numbers 𝐼(𝐽𝑃)=0(1+). We use five different gauge-link ensembles with 2+1 flavors of domain-wall fermions, including one at the physical pion mass, and treat the heavy ¯𝑏 quark within the framework of lattice nonrelativistic QCD. Our work improves upon previous similar computations by considering in addition to local four-quark interpolators also nonlocal two-meson interpolators and by performing a Lüscher analysis to extrapolate our results to infinite volume. We obtain a binding energy of (−128±24±10) MeV, corresponding to the mass (10476±24±10) MeV, which confirms the existence of a ¯𝑏¯𝑏𝑢𝑑 tetraquark that is stable with respect to the strong and electromagnetic interactions.
b̄b̄ud tetraquark resonances in the Born-Oppenheimer approximation using lattice QCD potentials
(2019)
We study tetraquark resonances for a pair of static antiquarks b¯b¯ in presence of two light quarks ud based on lattice QCD potentials. The system is treated in the Born-Oppenheimer approximation and we use the emergent wave method. We focus on the isospin I = 0 channel but take different angular momenta l of the heavy antiquarks b¯b¯ into account. Further calculations have already predicted a bound state for the l = 0 case with quantum numbers I(JP) = 0(1+). Performing computations for several angular momenta, we extract the phase shifts and search for T and S matrix poles in the second Riemann sheet. For angular momentum l = 1, we predict a tetraquark resonance with quantum numbers I(JP) = 0(1−), resonance mass m = 10576+4−4 MeV and decay width Γ = 112+90−103 MeV, which decays into two B mesons.
We use lattice QCD to investigate the existence of strong-interaction-stable antiheavy-antiheavy-light-light tetraquarks. We study the ¯𝑏¯𝑏𝑢𝑠 system with quantum numbers 𝐽𝑃=1+ as well as the ¯𝑏¯𝑐𝑢𝑑 systems with quantum numbers 𝐼(𝐽𝑃)=0(0+) and 𝐼(𝐽𝑃)=0(1+). We carry out computations on five gauge-link ensembles with 2+1 flavors of domain-wall fermions, including one at the physical pion mass. The bottom quarks are implemented using lattice nonrelativistic QCD, and the charm quarks using an anisotropic clover action. In addition to local diquark-antidiquark and local meson-meson interpolating operators, we include nonlocal meson-meson operators at the sink, which facilitates the reliable determination of the low-lying energy levels. We find clear evidence for the existence of a strong-interaction-stable ¯𝑏¯𝑏𝑢𝑠 tetraquark with binding energy (−86±22±10) MeV and mass (10609±22±10) MeV. For the ¯𝑏¯𝑐𝑢𝑑 systems we do not find any indication for the existence of bound states, but cannot rule out their existence either.
b̄b̄ud tetraquark resonances in the Born-Oppenheimer approximation using lattice QCD potentials
(2018)
We study tetraquark resonances using lattice QCD potentials for a pair of static antiquarks b¯b¯ in the presence of two light quarks ud. The system is treated in the Born-Oppenheimer approximation and we use the emergent wave method. We focus on the isospin I=0 channel, but consider different orbital angular momenta l of the heavy antiquarks b¯b¯. We extract the phase shifts and search for S and T matrix poles on the second Riemann sheet. For orbital angular momentum l=1 we find a tetraquark resonance with quantum numbers I(JP)=0(1−), resonance mass m=10576+4−4MeV and decay width Γ=112+90−103MeV, which can decay into two B mesons.
In this work we investigate the existence of bound states for doubly heavy tetraquark systems Q¯Q¯′qq′ in a full lattice-QCD computation, where heavy bottom quarks are treated in the framework of non-relativistic QCD. We focus on three systems with quark content b¯b¯ud, b¯b¯us and b¯c¯ud. We show evidence for the existence of b¯b¯ud and b¯b¯us bound states, while no binding appears to be present for b¯c¯ud. For the bound four-quark states we also discuss the importance of various creation operators and give an estimate of the meson-meson and diquark-antidiquark percentages.
In this work we investigate the existence of bound states for doubly heavy tetraquark systems Q¯Q¯′qq′ in a full lattice-QCD computation, where heavy bottom quarks are treated in the framework of non-relativistic QCD. We focus on three systems with quark content b¯b¯ud, b¯b¯us and b¯c¯ud. We show evidence for the existence of b¯b¯ud and b¯b¯us bound states, while no binding appears to be present for b¯c¯ud. For the bound four-quark states we also discuss the importance of various creation operators and give an estimate of the meson-meson and diquark-antidiquark percentages.
We present our recent results on antiheavy-antiheavy-light-light tetraquark systems using lattice QCD. Our study of the b¯b¯us four-quark system with quantum numbers JP=1+ and the b¯c¯ud four-quark systems with I(JP)=0(0+) and I(JP)=0(1+) utilizes scattering operators at the sink to improve the extraction of the low-lying energy levels. We found a bound state for b¯b¯us with Ebind,b¯b¯us=(−86±22±10)MeV, but no indication for a bound state in both b¯c¯ud channels. Moreover, we show preliminary results for b¯b¯ud with I(JP)=0(1+), where we used scattering operators both at the sink and the source. We found a bound state and determined its infinite-volume binding energy with a scattering analysis, resulting in Ebind,b¯b¯ud=(−103±8)MeV.