Refine
Has Fulltext
- yes (52)
Is part of the Bibliography
- no (52)
Keywords
- e +-e − Experiments (6)
- BESIII (3)
- Particle and Resonance Production (3)
- Charm Physics (2)
- Electroweak Interaction (2)
- Exotics (2)
- Quarkonium (2)
- Spectroscopy (2)
- Born cross section measurement (1)
- Branching fraction (1)
Institute
- Physik (46)
- Medizin (4)
- Biochemie, Chemie und Pharmazie (1)
- Geschichtswissenschaften (1)
Background: As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response.
Methods: This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively.
Results: Overall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70–1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50–1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed.
Conclusions: Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted.
Trial registration: This study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland-Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009.
The family of phytochrome photoreceptors contains proteins with different domain architectures and spectral properties. Knotless phytochromes are one of the three main subgroups classified by their distinct lack of the PAS domain in their photosensory core module, which is in contrast to the canonical PAS-GAF-PHY array. Despite intensive research on the ultrafast photodynamics of phytochromes, little is known about the primary kinetics in knotless phytochromes. Here, we present the ultrafast Pr ⇆ Pfr photodynamics of SynCph2, the best-known knotless phytochrome. Our results show that the excited state lifetime of Pr* (~200 ps) is similar to bacteriophytochromes, but much longer than in most canonical phytochromes. We assign the slow Pr* kinetics to relaxation processes of the chromophore-binding pocket that controls the bilin chromophore’s isomerization step. The Pfr photoconversion dynamics starts with a faster excited state relaxation than in canonical phytochromes, but, despite the differences in the respective domain architectures, proceeds via similar ground state intermediate steps up to Meta-F. Based on our observations, we propose that the kinetic features and overall dynamics of the ultrafast photoreaction are determined to a great extent by the geometrical context (i.e., available space and flexibility) within the binding pocket, while the general reaction steps following the photoexcitation are most likely conserved among the red/far-red phytochromes.
Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation and MGMT promoter methylation status. Finally, the role of HOTAIRM1 in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identified HOTAIRM1 as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation and MGMT promoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity upon HOTAIRM1 down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels upon HOTAIRM1 knock-down. HOTAIRM1 knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down of TGM2 mimicked the phenotype of HOTAIRM1 down-regulation in glioblastoma cells. Moreover, HOTAIRM1 modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role for HOTAIRM1 as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. Targeting HOTAIRM1 may be a promising new therapeutic approach.
The Born cross sections of the e+e− → D*+D*− and e+e− → D*+D− processes are measured using e+e− collision data collected with the BESIII experiment at center-of-mass energies from 4.085 to 4.600 GeV, corresponding to an integrated luminosity of 15.7 fb−1. The results are consistent with and more precise than the previous measurements by the Belle, Babar and CLEO collaborations. The measurements are essential for understanding the nature of vector charmonium and charmonium-like states.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Using 7.33 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.128 and 4.226~GeV, we observe for the first time the decay D±s→ωπ±η with a statistical significance of 7.6σ. The measured branching fraction of this decay is (0.54±0.12±0.04)%, where the first uncertainty is statistical and the second is systematic.
We report the first measurements of the absolute branching fractions of D0 → K0 Lϕ, D0 → K0Lη, D0 → K0Lω, and D0 → K0Lη0, by analyzing 2.93 fb−1 of eþe− collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector. Taking the world averages of the branching fractions of D0 → K0Sϕ, D0 → K0Sη, D0 → K0Sω, and D0 → K0Sη0, the K0S − K0L asymmetries RðD0; XÞ in these decay modes are obtained. The CP asymmetries in these decays are also determined. No significant CP violation is observed
We search for the semi-leptonic decays Λ + c → Λπ+π−e+νe and Λ + c → pK0 Sπ−e+νe in a sample of 4.5 fb−1 of e+e− annihilation data collected in the center-of-mass energy region between 4.600 GeV and 4.699 GeV by the BESIII detector at the BEPCII. No significant signals are observed, and the upper limits on the decay branching fractions are set to be B(Λ+c → Λπ+π−e+νe ) < 3.9 × 10−4 and B(Λ + c → pK0Sπ−e+νe ) < 3.3 × 10−4 at the 90% confidence level, respectively.
Based on 4.5 fb−1 data taken at seven center-of-mass energies ranging from 4.600 to 4.699 GeV with the BESIII detector at the BEPCII collider, we measure the branching fractions of Λ + c → Σ + + hadrons relative to Λ + c → Σ +π +π −. Combining with the world average branching fraction of Λ + c → Σ +π +π −, their branching fractions are measured to be (0.377 ± 0.042 ± 0.020 ± 0.021)% for Λ + c → Σ +K+K−, (0.200 ± 0.023 ± 0.011 ± 0.011)% for Λ + c → Σ+K+π−, (0.414 ± 0.080 ± 0.030 ± 0.023)% for Λ + c → Σ +φ and (0.197 ± 0.036 ± 0.009 ± 0.011)% for Λ + c → Σ +K+K−(non-φ). In all the above results, the first uncertainties are statistical, the second are systematic and the third are from external input of the branching fraction of Λ + c → Σ +π +π −. Since no signal for Λ + c → Σ +K+π−π 0 is observed, the upper limit of its branching fraction is determined to be 0.13% at the 90% confidence level.
With data samples collected with the BESIII detector at seven energy points at √s = 3.68 − 3.71 GeV, corresponding to an integrated luminosity of 333 pb−1, we present a study of the Λ transverse polarization in the e+e− → ΛΛ¯ reaction. The signifcance of polarization by combining the seven energy points is found to be 2.6σ including the systematic uncertainty, which implies a non-zero phase between the transition amplitudes of the ΛΛ¯ helicity states. The modulus ratio and the relative phase of EM-psionic form factors combined with all energy points are measured to be RΨ = 0.71+0.10−0.10 ± 0.03 and ∆ΦΨ = 23+8.8−8.0 ± 1.6◦, where the frst uncertainties are statistical and the second systematic.
Using (1.0087±0.0044)×1010 𝐽/𝜓 events collected by the BESIII detector at the BEPCII collider, we report the first search for the baryon and lepton number violating decays Ξ0→𝐾−𝑒+ with Δ(𝐵−𝐿)=0 and Ξ0→𝐾+𝑒− with |Δ(𝐵−𝐿)|=2, where 𝐵 (𝐿) is the baryon (lepton) number. While no signal is observed, the upper limits on the branching fractions of these two decays are set to ℬ(Ξ0→𝐾−𝑒+)<3.6×10−6 and ℬ(Ξ0→𝐾+𝑒−)<1.9×10−6 at the 90% confidence level, respectively. These results offer a direct probe of baryon number violating interactions involving a strange quark.
The singly Cabibbo-suppressed decay D+s → K+π+π−π0 is observed by using a data set corresponding to an integrated luminosity of 6.32 fb−1 recorded by the BESIII detector at the centre-of-mass energies between 4.178 and 4.226 GeV. The first amplitude analysis of D+s → K+π+π−π0 reveals the sub-structures in this decay and determines the fractions and relative phases of different intermediate processes. The dominant intermediate process is D+s → K∗0ρ+, with a fit fraction of (40.5 ± 2.8stat. ± 1.5syst.)%. With the detection efficiency based on our amplitude analysis, the absolute branching fraction forD+s → K+π+π−π0 is measured to be (9.75 ± 0.54stat. ± 0.17syst.) × 10−3.
We report a search for a dark photon using 14.9~fb−1 of e+e− annihilation data taken at center-of-mass energies from 4.13 to 4.60~GeV with the BESIII detector operated at the BEPCII storage ring. The dark photon is assumed to be produced in the radiative annihilation process of e+e− and to predominantly decay into light dark matter particles, which escape from the detector undetected. The mass range from 1.5 to 2.9~GeV is scanned for the dark photon candidate, and no significant signal is observed. The mass dependent upper limits at the 90% confidence level on the coupling strength parameter ϵ for a dark photon coupling with an ordinary photon vary between 1.6×10−3 and 5.7×10−3.
Precision measurements of the semileptonic decays 𝐷+𝑠→𝜂𝑒+𝜈𝑒 and 𝐷+𝑠→𝜂′𝑒+𝜈𝑒 are performed with 7.33 fb−1 of 𝑒+𝑒− collision data collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector. The branching fractions obtained are ℬ(𝐷+𝑠→𝜂𝑒+𝜈𝑒) = (2.255±0.039stat±0.051syst)% and ℬ(𝐷+𝑠→𝜂′𝑒+𝜈𝑒)=(0.810±0.038stat±0.024syst)%. Combining these results with the ℬ(𝐷+→𝜂𝑒+𝜈𝑒) and ℬ(𝐷+→𝜂′𝑒+𝜈𝑒) obtained from previous BESIII measurements, the 𝜂−𝜂′ mixing angle in the quark flavor basis is determined to be 𝜙P=(40.0±2.0stat±0.6syst)°. Moreover, from the fits to the partial decay rates of 𝐷+𝑠→𝜂𝑒+𝜈𝑒 and 𝐷+𝑠→𝜂′𝑒+𝜈𝑒, the products of the hadronic transition form factors 𝑓𝜂(′)+(0) and the modulus of the 𝑐→𝑠 Cabibbo-Kobayashi-Maskawa matrix element |𝑉𝑐𝑠| are determined by using different hadronic transition form factor parametrizations. Based on the two-parameter series expansion, the products 𝑓𝜂+(0)|𝑉𝑐𝑠| = 0.4519±0.0071stat±0.0065syst and 𝑓𝜂′+(0)|𝑉𝑐𝑠| = 0.525±0.024stat±0.009syst are extracted. All results determined in this work supersede those measured in the previous BESIII analyses based on the 3.19 fb−1 subsample of data at 4.178 GeV.
First study of reaction Ξ⁰n → Ξ⁻ p using Ξ⁰-nucleus scattering at an electron-positron collider
(2023)
Using ð1.0087 0.0044Þ × 1010 J=ψ events collected with the BESIII detector at the BEPCII storage ring, the process Ξ0n → Ξ−p is studied, where the Ξ0 baryon is produced in the process J=ψ → Ξ0Ξ¯ 0 and the neutron is a component of the 9 Be, 12C, and 197Au nuclei in the beam pipe. A clear signal is observed with a statistical significance of 7.1σ. The cross section of the reaction Ξ0 þ 9 Be → Ξ− þ p þ 8 Be is determined to be σðΞ0 þ 9 Be → Ξ− þ p þ 8 BeÞ¼ð22.1 5.3stat 4.5sysÞ mb at the Ξ0 momentum of 0.818 GeV=c, where the first uncertainty is statistical and the second is systematic. No significant H-dibaryon signal is observed in the Ξ−p final state. This is the first study of hyperon-nucleon interactions in electron-positron collisions and opens up a new direction for such research.
Using an 𝑒+𝑒− collision data sample of (27.08±0.14)×108 𝜓(3686) events collected by the BESIII detector, we report the first observation of 𝜒𝑐𝐽→Ω−¯Ω+ (𝐽=0, 1, 2) decays with significances of 5.6𝜎, 6.4𝜎, and 18𝜎, respectively, where the 𝜒𝑐𝐽 mesons are produced in the radiative 𝜓(3686) decays. The branching fractions are determined to be ℬ(𝜒𝑐0→Ω−¯Ω+) = (3.51±0.54±0.29)×10−5, ℬ(𝜒𝑐1→Ω−¯Ω+)=(1.49±0.23±0.10)×10−5, and ℬ(𝜒𝑐2→Ω−¯Ω+)=(4.52±0.24±0.18)×10−5, where the first and second uncertainties are statistical and systematic, respectively.
Using a data sample corresponding to an integrated luminosity of 11.3 fb−1 collected at center-of-mass energies from 4.23 to 4.70 GeV with the BESIII detector, we observe the process e+e− → π0π0ψ2(3823) for the first time with a statistical significance of 6.0 standard deviations. The ratio of average cross sections for e+e− → π0π0ψ2(3823) and π+π−ψ2(3823) is determined to be R = σ[e+e− → π0π0ψ2(3823)] σ[e+e−→π+π−ψ2(3823)] = 0.57 ± 0.14 ± 0.05, which is consistent with expectations from isospin symmetry. Here and below, the first uncertainties are statistical and the second are systematic. The mass of the ψ2(3823) is measured to be M[ψ2(3823)] = 3824.5±2.4±1.0 MeV/c2. Due to the limited data sample, an upper limit of 18.8 MeV at 90% confidence level is set on the intrinsic width of ψ2(3823).