Charm mixing in the Standard Model

In this talk we report on a study on the mixing of neutral charmed mesons and argue that, at the present stage, a CP violating weak phase of the order of some per mille can not be excluded in the Standard Model. It is shown how some, seemingly reasonable, simplifying assumptions about CKM couplings lead to the wrong conclusion that CP violation of this amount is an unambiguous indication of new physics. The presented results rely on a recent short-distance analysis of the ∆C = 2 transition, which con- firms the expectation that the dominant contribution is due to effects of flavour symmetry breaking appearing in higher orders of the Heavy Quark Expansion. We investigate meson-antimeson transitions with an intermediate state coupling to the meson’s sea quark background, present in dimension 10 and 12, using a factorisation approach to simplify the operator basis. On account of a lifting of GIM suppression by one power of ms/mc, the contribution to y = ∆Γ/2Γ is found to exceed that of the formally leading dimension six by a factor close to ten

Memory Bounded Open-Loop Planning in Large POMDPs using Thompson Sampling

State-of-the-art approaches to partially observable planning like POMCP are based on stochastic tree search. While these approaches are computationally efficient, they may still construct search trees of considerable size, which could limit the performance due to restricted memory resources. In this paper, we propose Partially Observable Stacked Thompson Sampling (POSTS), a memory bounded approach to open-loop planning in large POMDPs, which optimizes a fixed size stack of Thompson Sampling bandits. We empirically evaluate POSTS in four large benchmark problems and compare its performance with different tree-based approaches. We show that POSTS achieves competitive performance compared to tree-based open-loop planning and offers a performance-memory tradeoff, making it suitable for partially observable planning with highly restricted computational and memory resources.Comment: Presented at AAAI 201

The drug development pipeline for glioblastoma: a cross sectional assessment of the FDA orphan drug product designation database

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumour among adult patients and represents an almost universally fatal disease. Novel therapies for GBM are being developed under the orphan drug legislation and the knowledge on the molecular makeup of this disease has been increasing rapidly. However, the clinical outcomes in GBM patients with currently available therapies are still dismal. An insight into the current drug development pipeline for GBM is therefore of particular interest. OBJECTIVES: To provide a quantitative clinical-regulatory insight into the status of FDA orphan drug designations for compounds intended to treat GBM. METHODS: Quantitative cross-sectional analysis of the U.S. Food and Drug Administration Orphan Drug Product database between 1983 and 2020. STROBE criteria were respected. RESULTS: Four orphan drugs out of 161 (2,4%) orphan drug designations were approved for the treatment for GBM by the FDA between 1983 and 2020. Fourteen orphan drug designations were subsequently withdrawn for unknown reasons. The number of orphan drug designations per year shows a growing trend. In the last decade, the therapeutic mechanism of action of designated compounds intended to treat glioblastoma shifted from cytotoxic drugs (median year of designation 2008) to immunotherapeutic approaches and small molecules (median year of designation 2014 and 2015 respectively) suggesting an increased focus on precision in the therapeutic mechanism of action for compounds the development pipeline. CONCLUSION: Despite the fact that current pharmacological treatment options in GBM are sparse, the drug development pipeline is steadily growing. In particular, the surge of designated immunotherapies detected in the last years raises the hope that elaborate combination possibilities between classical therapeutic backbones (radiotherapy and chemotherapy) and novel, currently experimental therapeutics may help to provide better therapies for this deadly disease in the future

Short distance D-Dbar mixing

We review the status of Standard Model predictions for lifetimes and mixing rates of charmed mesons. It is shown that the short distance approach is able to reproduce τ (D+)/τ (D0) at leading order in the 1/mc expansion. SU(3) violating effects from interactions with the soft hadronic background are identified as the dominant contribution to the D–D mixing rate. We discuss the contribution from operators of dimension nine, which is able to enhance the neutral charm width splitting by a factor of order ten and comment on possible CP violation in mixing

Recognition of two distinct elements in the RNA substrate by the RNA-binding domain of the T. thermophilus DEAD box helicase Hera

DEAD box helicases catalyze the ATP-dependent destabilization of RNA duplexes. Whereas duplex separation is mediated by the helicase core shared by all members of the family, flanking domains often contribute to binding of the RNA substrate. The Thermus thermophilus DEAD-box helicase Hera (for “heat-resistant RNA-binding ATPase”) contains a C-terminal RNA-binding domain (RBD). We have analyzed RNA binding to the Hera RBD by a combination of mutational analyses, nuclear magnetic resonance and X-ray crystallography, and identify residues on helix α1 and the C-terminus as the main determinants for high-affinity RNA binding. A crystal structure of the RBD in complex with a single-stranded RNA resolves the RNA–protein interactions in the RBD core region around helix α1. Differences in RNA binding to the Hera RBD and to the structurally similar RBD of the Bacillus subtilis DEAD box helicase YxiN illustrate the versatility of RNA recognition motifs as RNA-binding platforms. Comparison of chemical shift perturbation patterns elicited by different RNAs, and the effect of sequence changes in the RNA on binding and unwinding show that the RBD binds a single-stranded RNA region at the core and simultaneously contacts double-stranded RNA through its C-terminal tail. The helicase core then unwinds an adjacent RNA duplex. Overall, the mode of RNA binding by Hera is consistent with a possible function as a general RNA chaperone

Krise der Männlichkeit als identitäres Spielfeld: zum Sammelband ‚Der verfasste Mann: Männlichkeiten in der Literatur und Kultur um 1900‘ von Gregor Schuhen

Rez. Gregor Schuhen, Hrsg., Der verfasste Mann: Männlichkeiten in der Literatur und Kultur um 1900 (Bielefeld: transcript Verlag, 2014)