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Afghanistan-Krieg
(2021)
Retinol-binding protein 4 (RBP4) is the major transport protein for retinol in blood. Recent evidence from genetic mouse models shows that circulating RBP4 derives exclusively from hepatocytes. Because RBP4 is elevated in obesity and associates with the development of glucose intolerance and insulin resistance, we tested whether a liver-specific overexpression of RBP4 in mice impairs glucose homeostasis. We used adeno-associated viruses (AAV) that contain a highly liver-specific promoter to drive expression of murine RBP4 in livers of adult mice. The resulting increase in serum RBP4 levels in these mice was comparable with elevated levels that were reported in obesity. Surprisingly, we found that increasing circulating RBP4 had no effect on glucose homeostasis. Also during a high-fat diet challenge, elevated levels of RBP4 in the circulation failed to aggravate the worsening of systemic parameters of glucose and energy homeostasis. These findings show that liver-secreted RBP4 does not impair glucose homeostasis. We conclude that a modest increase of its circulating levels in mice, as observed in the obese, insulin-resistant state, is unlikely to be a causative factor for impaired glucose homeostasis.
Leveraging large-deviation statistics to decipher the stochastic properties of measured trajectories
(2021)
Extensive time-series encoding the position of particles such as viruses, vesicles, or individualproteins are routinely garnered insingle-particle tracking experiments or supercomputing studies.They contain vital clues on how viruses spread or drugs may be delivered in biological cells.Similar time-series are being recorded of stock values in financial markets and of climate data.Such time-series are most typically evaluated in terms of time-averaged mean-squareddisplacements (TAMSDs), which remain random variables for finite measurement times. Theirstatistical properties are different for differentphysical stochastic processes, thus allowing us toextract valuable information on the stochastic process itself. To exploit the full potential of thestatistical information encoded in measured time-series we here propose an easy-to-implementand computationally inexpensive new methodology, based on deviations of the TAMSD from itsensemble average counterpart. Specifically, we use the upper bound of these deviations forBrownian motion (BM) to check the applicability of this approach to simulated and real data sets.By comparing the probability of deviations fordifferent data sets, we demonstrate how thetheoretical bound for BM reveals additional information about observed stochastic processes. Weapply the large-deviation method to data sets of tracer beads tracked in aqueous solution, tracerbeads measured in mucin hydrogels, and of geographic surface temperature anomalies. Ouranalysis shows how the large-deviation properties can be efficiently used as a simple yet effectiveroutine test to reject the BM hypothesis and unveil relevant information on statistical propertiessuch as ergodicity breaking and short-time correlations.
Coordinated subjects often show variable number agreement with the finite verb, but linguistic approaches to this phenomenon have rarely been informed by systematically collected data. We report the results from three experiments investigating German speakers' agreement preferences with complex subjects joined by the correlative conjunctions sowohl horizontal ellipsis als auch ('both horizontal ellipsis and'), weder horizontal ellipsis noch ('neither horizontal ellipsis nor') or entweder horizontal ellipsis oder ('either horizontal ellipsis or'). We examine to what extent conjunction type and a conjunct's relative proximity to the verb affect the acceptability and processibility of singular vs. plural agreement. Experiment 1 was an untimed acceptability rating task, Experiment 2 a timed sentence completion task, and Experiment 3 was a self-paced reading task. Taken together, our results show that number agreement with correlative coordination in German is primarily determined by a default constraint triggering plural agreement, which interacts with linear order and semantic factors. Semantic differences between conjunctions only affected speakers' agreement preferences in the absence of processing pressure but not their initial agreement computation. The combined results from our offline and online experimental measures of German speakers' agreement preferences suggest that the constraints under investigation do not only differ in their relative weighting but also in their relative timing during agreement computation.
Un dandy de zapatos gastados
(2021)
El comienzo podrían ser dos imágenes de Vallejo en París. La primera la extraigo de la más reciente biografía del escritor peruano, César Vallejo: A Literary Biography, obra del hispanista británico Stephen Hart. Refiere Hart que en sus primeros años en París la situación de Vallejo era tan precaria que cuando viajaba en tren evitaba descender del vagón hasta que no se hubiera detenido del todo para no desgastar su único par de zapatos. En cierta ocasión, yendo con unos amigos y topándose con una acera encharcada por la ruptura de una boca de riego, Vallejo prefirió dar media vuelta y despedirse de sus amigos antes que arriesgarse a arruinar sus zapatos atravesando el charco (108). Quisiera contrastar esta imagen, que sintetiza la penuria económica que marcó la vida de Vallejo en París y en general los quince años que pasó en Europa desde que abandonó el Perú en 1923 hasta su muerte en 1938, con la imagen que propone una fotografía (véase Fig. 1).
Es una fotografía muy conocida: tomada en 1929 por Juan Domingo Córdoba en el curso de un paseo veraniego por Versalles, se ha convertido en una suerte de imagen emblemática, reproducida en numerosas reediciones de la obra de Vallejo. De hecho, lo que a mí siempre me llamó la atención en esta imagen es la pose. La pose, y la elegancia del atuendo. Consideremos por un momento lo atildado del traje, el coqueto pañuelo que asoma del bolsillo superior de la chaqueta, el anillo con un ágata negra engastada en el dedo corazón, el sombrero de fieltro dejado al desgaire en la pierna, el señorial bastón—o la corbata anudada en pajarita con que aparece en otra fotografía contemporánea (véase Fig. 2). Si hubiera que definir en una palabra la elegancia de esa pose, yo diría que es la pose de un dandy. Un dandy de zapatos gastados.
En los múltiples transtierros de Vallejo, y en particular en los quince años que vivió en París, coexisten así pues la precariedad económica del emigrante y el cosmopolitismo del viajero culto.
A convenient method for the synthesis of gamma-spirolactams in only three steps is described. Birch reduction of inexpensive and commercially available aromatic carboxylic acids in the presence of chloroacetonitrile affords nitriles in moderate to good yields. Suitable precursors are methyl-substituted benzoic acids, naphthoic, and anthroic acid. Subsequent catalytic hydrogenation proceeds smoothly with PtO2 or Raney Ni as catalysts and lactams are isolated in excellent yields and stereoselectivities. Thus, up to 3 new stereogenic centers can be constructed as sole diastereomers from achiral benzoic acids. Furthermore, it is possible to control the degree of saturation at different pressures, affording products with 0, 1, or 2 double bonds. Overall, more than 15 new gamma-spirolactams have been synthesized in analytically pure form.
Influence of functional groups on the ene reaction of singlet oxygen with 1,4-cyclohexadienes
(2021)
The photooxygenation of 1,4-cyclohexadienes has been studied with a special focus on regio- and stereoselectivities. In all examples, only the methyl-substituted double bond undergoes an ene reaction with singlet oxygen, to afford hydroperoxides in moderate to good yields. We explain the high regioselectivities by a "large-group effect" of the adjacent quaternary stereocenter. Nitriles decrease the reactivity of singlet oxygen, presumably by quenching, but can stabilize proposed per-epoxide intermediates by polar interactions resulting in different stereoselectivities. Spiro lactams and lactones show an interesting effect on regio- and stereoselectivities of the ene reactions. Thus, singlet oxygen attacks the double bond preferentially anti to the carbonyl group, affording only one regioisomeric hydroperoxide. If the reaction occurs from the opposite face, the other regioisomer is exclusively formed by severe electrostatic repulsion in a perepoxide intermediate. We explain this unusual behavior by the fixed geometry of spiro compounds and call it a "spiro effect" in singlet oxygen ene reactions.
In the absence of a stranded auxiliary or modal, VP-topicalization in most Germanic languages gives rise to the presence of a dummy verb meaning 'do'. Cross-linguistically, this is a rather uncommon strategy as comparable VP-fronting constructions in other languages, e.g. Hebrew, Polish, and Portuguese, among many others, exhibit verb doubling. A comparison of several recent approaches to verb doubling in VP-fronting reveals that it is the consequence of VP-evacuating head movement of the verb to some higher functional head, which saves the (low copy of the) verb from undergoing copy deletion as part of the low VP copy in the VP-topicalization dependency. Given that almost all Germanic languages have such V-salvaging head movement, namely V-to-C movement, but do not show verb doubling, this paper suggests that V-raising is exceptionally impossible in VP-topicalization clauses and addresses the question of why it is blocked. After discussing and rejecting some conceivable explanations for the lack of verb doubling, I propose that the blocking effect arises from a bleeding interaction between V-to-C movement and VP-to-SpecCP movement. As both operations are triggered by the same head, i.e. C, the VP is always encountered first by a downward search algorithm. Movement of VP then freezes it and its lower copies for subextraction precluding subsequent V-raising. Crucially, this implies that there is no V-to-T raising in most Germanic languages. V2 languages with V-to-T raising, e.g. Yiddish, are correctly predicted to not exhibit the blocking effect.