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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.
In this paper, we argue that by making a more detailed distinction of theta-roles, while at the same time investigating the correlation of case marking, theta-role assignment, and eventuality types, we can describe different psych-verb subclasses and explain their alignment patterns in Spanish and Korean. We propose a neo-Davidsonian treatment of psych-verbs in HPSG that allows us to account for the underspecification of theta-roles which are modeled in an inheritance hierarchy for semantic relations. By assuming linking properties modeled lexically, we can constrain the properties for psych-verbs which shows the mapping of semantic arguments (i.e. experiencer, stimulus-causer, subject matter and target) to the elements in the argument structure. The type hierarchy and lexical rules proposed here capture the alternation in case marking not only of the experiencer (as traditionally assumed in the literature), but also of the stimulus. This analysis leads us to a new fourfold classification of psych-verbs for both languages.
The paper shows how the plural semantic ideas of (Sternefeld, 1998) can be captured in Lexical Resource Semantics, a system of underspecied semantics. It is argued that Sternefeld's original approach, which allows for the unrestricted insertion of pluralisation into Logical Form, suffers from a problem originally pointed out by Lasersohn (1989) with respect to the analysis offered by Gillon (1987). The problem is shown to stem from repeated pluralisation of the same verbal argument and to be amenable to a simple solution in the proposed lexical analysis, which allows for restricting the pluralisations that can be inserted. The paper further develops an account of maximalisation of pluralities as needed to obtain the correct readings for sentences with quantiers that are not upward monotone. Such an account is absent in the orginal system in (Sternefeld, 1998). The present account makes crucial use of the possibility to have distinct constituents contribute identical semantic material offered by LRS and employs it in an analysis of maximalisation in terms of polyadic quantication.
We present an analysis of clausal nominalization developed in the context of the LinGO Grammar Matrix (Bender et al., 2002, 2010) to support the addition of subordinate clauses to the grammar customization framework. In particular, we examine the typological variation of nominalized clausal complements and nominalized clausal modifiers. To account for the range of variation in nominalized clauses across the world's languages and to support linguists in exploring alternative analyses, we propose a flexible library of analyses, allowing nominalization of the clause to occur at the V, VP or S level.
The paper addresses verbal agreement in German sign language from a constraint-based perspective. Based on Meir's Agreement Morphology Principles it presents an HPSG analysis of plain, regular and backwards agreement verbs that models the interaction between phonological (manual) features and syntactico-semantic relationships within a verbal sign by well-defined lexical restrictions. We argue that a sign-based declarative analysis can provide an elegant approach to agreement in sign language since it allows to exploit cross-modular constraints within grammar, and hence permits a direct manipulation of all relevant phonological features of a verb depending on its syntactic and semantic properties.
I describe an analysis of valence-changing verbal morphology implemented as a library extending the LinGO Grammar Matrix customization system. This analysis is based on decomposition of these operations into rule components, which in turn are expressed as lexical rule supertypes that implement specific, isolatable constraints. I also show how common variations of these constraints can be abstracted and parameterized by their axes of variation. I then demonstrate how these constraints can be recomposed in various combinations to provide broad coverage of the typological variation of valence change found in the world's languages. I evaluate the coverage of this library on five held-out world languages that exhibit these phenomena, achieving 79% coverage and 2% overgeneration.
In this paper, we study Old French declension, a system which exhibits the theoretically challenging phenomenon of morphological reversal (Baerman, 2007). Furthermore, the declension system of Old French only recognises a single exponent -s, which marks different case/number combinations in different paradigms, contrasting with the unmarked form. We show that reversal is only one of several syncretism patterns found in the language and propose that Old French declension is best understood in terms of two systematic syncretisms: a natural split between singular and plural for feminines, and a Paninian split for masculines that systematically marks the objective plural. Reversal, and other seemingly morphomic splits arise as a result of idiosyncrasy in the NOM.SG cell, comprising inflection class-specific s-marking, as well as stem alternation and overabundance. We provide a formal analysis in terms of Information-based Morphology (Crysmann & Bonami, 2016) that effortlessly captures the systematic splits, as well as the variation in the nominative singular. We suggest that the high degree of idiosyncrasy in this cell paired with the reduced frequency of overt nominative NPs when compared to objective NPs may serve to explain why the system was actually quite short-lived.
Dutch is well-known for the formation of verb clusters. A characteristic aspect of such constructions is that the order of the verbs may differ from the order in which they are selected. Across the Dutch language area verb clusters show different types of word order variation. This paper proposes a constructivist account of word order variation in Dutch verb clusters. Linearization is not modelled in terms of the GVOR feature, after Kathol (2000). Instead, it relies on the bidimensional phrase hierarchy initiated by Ginzburg & Sag (2000), which is extended for the analysis of constructions with verb clusters. This proposal accounts for the most common instances of word order variation in Dutch verb clusters, and it can be easily adapted to model a specific variety or dialect.
Rapidity-odd directed flow measurements at midrapidity are presented for Λ, Λ¯, K±, K0s and ϕ at sNN−−−−√= 7.7, 11.5, 14.5, 19.6, 27, 39, 62.4 and 200 GeV in Au+Au collisions recorded by the STAR detector at the Relativistic Heavy Ion Collider. These measurements greatly expand the scope of data available to constrain models with differing prescriptions for the equation of state of quantum chromodynamics. Results show good sensitivity for testing a picture where flow is assumed to be imposed before hadron formation and the observed particles are assumed to form via coalescence of constituent quarks. The pattern of departure from a coalescence-inspired sum-rule can be a valuable new tool for probing the collision dynamics.
Transverse spin transfer to Λ and ¯Λ hyperons in polarized proton-proton collisions at √𝑠=200 GeV
(2018)
The transverse spin transfer from polarized protons to Λ and Λ¯ hyperons is expected to provide sensitivity to the transversity distribution of the nucleon and to the transversely polarized fragmentation functions. We report the first measurement of the transverse spin transfer to Λ and Λ¯ along the polarization direction of the fragmenting quark, DTT, in transversely polarized proton-proton collisions at s√=200GeV with the STAR detector at RHIC. The data correspond to an integrated luminosity of 18pb−1 and cover the pseudorapidity range |η|<1.2 and transverse momenta pT up to 8GeV/c. The dependence on pT and η are presented. The DTT results are found to be comparable with a model prediction, and are also consistent with zero within uncertainties.