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We search for rare decays of D mesons to hadrons accompany with an electron-positron pair (h(h')e+e−), using an e+e− collision sample corresponding to an integrated luminosity of 2.93 fb−1 collected with the BESIII detector at s√ = 3.773 GeV. No significant signals are observed, and the corresponding upper limits on the branching fractions at the 90% confidence level are determined. The sensitivities of the results are at the level of 10−5∼10−6, providing a large improvement over previous searches.
In integrative structural biology/hybrid modeling approaches, we integrate structural models of macromolecules and experimental data to obtain faithful representations of the structures underlying the data. For example, in ensemble refinement by reweighting we first generate structural ensembles of flexible and dynamic biological macromolecules in molecular simulations. In a subsequent reweighting step, we refine the statistical weights of the structures to strike a balance between the information provided by simulations and by experimental data. For the "Bayesian inference of ensembles" approach (BioEn), we present two complementary methods to solve the underlying challenging high-dimensional optimization problem. We systematically investigate reliability, accuracy, and efficiency of these methods and integrate molecular dynamics simulations of the disordered peptide Ala-5 and NMR J-couplings. We provide an open-source library free of charge at https://github.com/bio-phys/BioEn.
Tubulogenesis is essential for the formation and function of internal organs. One such organ is the trachea, which allows gas exchange between the external environment and the lungs. However, the cellular and molecular mechanisms underlying tracheal tube development remain poorly understood. Here, we show that the potassium channel KCNJ13 is a critical modulator of tracheal tubulogenesis. We identify Kcnj13 in an ethylnitrosourea forward genetic screen for regulators of mouse respiratory organ development. Kcnj13 mutants exhibit a shorter trachea as well as defective smooth muscle (SM) cell alignment and polarity. KCNJ13 is essential to maintain ion homeostasis in tracheal SM cells, which is required for actin polymerization. This process appears to be mediated, at least in part, through activation of the actin regulator AKT, as pharmacological increase of AKT phosphorylation ameliorates the Kcnj13 mutant trachea phenotypes. These results provide insights into the role of ion homeostasis in cytoskeletal organization during tubulogenesis.
Abstract
Inhibition of midbrain dopamine neurons is thought to underlie the signaling of events that are less rewarding than expected and drive learning based on these negative prediction errors. It has recently been shown that Kv4.3 channels influence the integration of inhibitory inputs in specific subpopulations of dopamine neurons. The functional properties of Kv4.3 channels are themselves strongly determined by the binding of auxiliary β-subunits; among them KChIP4a stands-out for its unique combination of modulatory effects. These include decreasing surface membrane trafficking and slowing inactivation kinetics. Therefore, we hypothesized that KChIP4a expression in dopamine neurons could play a crucial role in behavior, in particular by affecting the computation of negative prediction errors. We developed a mouse line where the alternative exon that codes for the KChIP4a splice variant was selectively deleted in midbrain dopamine neurons. In a reward-based reinforcement learning task, we observed that dopamine neuron-specific KChIP4a deletion selectively accelerated the rate of extinction learning, without impacting the acquisition of conditioned responses. We further found that this effect was due to a faster decrease in the initiation rate of goal-directed behaviors, and not faster increases in action disengagement. Furthermore, computational fitting of the behavioral data with a Rescorla-Wagner model confirmed that the observed phenotype was attributable to a selective increase in the learning rate from negative prediction errors. Finally, KChIP4a deletion did not affect performance in other dopamine-sensitive behavioral tasks that did not involve learning from disappointing events, including an absence of effects on working memory, locomotion and novelty preference. Taken together, our results demonstrate that an exon- and midbrain dopamine neuron-specific deletion of an A-type K+ channel β-subunit leads to a selective gain of function in extinction learning.
One Sentence Summary
Exon- and midbrain dopamine neuron-specific deletion of the Kv4 channel β-subunit KChIP4a selectively accelerates extinction learning
We examine the fine structure of clausal right-node raising constructions in Japanese, and argue that there are sentences in which a tensed verb is right-node-raised out of coordinated tensed clauses as well as sentences in which a verb stem is right-node-raised out of coordinated tenseless phrases. In the latter case, the tense morpheme has to be assumed to take a tenseless complement clause, and we note that the existence of such a structure contradicts the so-called lexicalist hypothesis, according to which a verb stem and the tense morpheme immediately following it always form a morphosyntactic constituent.
In this paper we describe insights gained from building an extension to the LinGO Grammar Matrix customization system to cover adnominal possessive phrases. We show how the wide range of such constructions attested in the world's languages can be handled with the typical major phrase types used in HPSG and discuss the value of feature bundling in the multilingual grammar engineering context.
This study aims to analyze and develop a detailed model of syntax and semantics of passive sentences in standard Indonesian in the framework of Head-Driven Phrase Structure Grammar (HPSG) (Pollard & Sag, 1994; Sag et al., 2003) and Minimal Recursion Semantics (MRS) (Copestake et al., 2005), explicit enough to be interpreted by a computer, focusing on implementation rather than theory. There are two main types of passive in Indonesian, following Sneddon et al. (2010, pp. 256-260) and Alwi et al. (2014, pp. 352-356), called 'passive type 1' (P1) and 'passive type 2' (P2). Both types were analyzed and implemented in the Indonesian Resource Grammar (INDRA), a computational grammar for Indonesian (Moeljadi et al., 2015).
The copula construction in Hebrew has received much attention in the linguistic literature. Nevertheless, one non-canonical variant has been largely neglected. In this variant the copula, flanked by two NPs, exhibits agreement with the post-copular NP, contrary to the canonical variant, where the agreement controller is the initial NP. This phenomenon challenges the notion of subject and its relation to agreement. The current corpus-based study investigates the word order and agreement patterns exhibited by the Hebrew copular constructions and shows that their distribution is largely motivated by information structure considerations. The proposed analysis accounts for the syntactic symmetry and semantic asymmetry between the two NPs.