One specific instantiation of the storm-and-stress view of adolescence is the idea that “normal” adolescence involves high-risk substance use behaviors. However, although uptake of some substance use behaviors is more common during adolescence than other life stages, it is clear that not all adolescents engage in risky substance use—and among those who do, there is much variation in emotional, behavioral, and contextual precursors of this behavior. One such set of predictors forms the internalizing pathway to substance use disorder, whereby internalizing (...) symptoms in childhood such as negative affect and anxiety set off a chain of consequences culminating in high-risk substance use in late adolescence. However, findings linking internalizing symptoms to substance use are mixed, and it is clear that this link varies across adolescents and contexts. One heretofore unanswered question is whether and how geographic location, specifically whether the adolescent lives in an urban or rural location, moderates this link. The current report is a secondary analysis of data from the Longitudinal Study of Australian Children, in which we examined the link between internalizing symptoms in childhood and initiation of substance use through age 19. Using a multiple event process survival mixture model, we identified three trajectories of substance use initiation in adolescence: one characterized by near-complete abstinence until late adolescence, another by earlier initiation of alcohol, nicotine, and cannabis, and another by early initiation of these substances and later initiation of more hazardous drugs such as cocaine and methamphetamine. Although childhood externalizing symptoms increased the risk of being in the second or third class, internalizing symptoms decreased risk when rural and non-rural adolescents were considered together. Few effects of rurality were found, but the negative relationship between internalizing at age 10 and high-risk substance use was only observed among non-rural adolescents. This finding, which was inconsistent with our initial predictions that rurality might confer higher risk for substance use, instead suggests a potentially protective effect of internalizing symptoms for engagement in risky substance use which may differ based on an adolescent’s geographical context. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)

© 2017. The American Astronomical Society. All rights reserved.We present new observations of the low-mass companion to HD 984 taken with the Gemini Planet Imager as a part of the GPI Exoplanet Survey campaign. Images of HD 984 B were obtained in the J and H bands. Combined with archival epochs from 2012 and 2014, we fit the first orbit to the companion to find an 18 au orbit with a 68% confidence interval between 14 and 28 au, an eccentricity (...) of 0.18 with a 68% confidence interval between 0.05 and 0.47, and an inclination of 119°with a 68% confidence interval between 114°and 125°. To address the considerable spectral covariance in both spectra, we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation. Using the split spectra, we compare them to known spectral types using field brown dwarf and low-mass star spectra and find a best-fit match of a field gravity M6.5 ±1.5 spectral type with a corresponding temperature of K. Photometry of the companion yields a luminosity of log=2.88 ± 0.07 dex with DUSTY models. Mass estimates, again from DUSTY models, find an age-dependent mass of 34 ±1 to 95 ±4 M Jup. These results are consistent with previous measurements of the object. (shrink)

In 1898 men and women from all over the world converged on Alaska. Gold had been discovered. In the Yukon Territory, all winter long eager gold seekers struggled over the mountain passes connecting Canada with the United States. A small group of photographers chronicled this epic, creating images of men and women laboring through blinding snowstorms over the windswept, ice-covered mountains. One of that group was a young Swedish immigrant by the name of P. E. Larson. Frozen in Silver documents (...) how this man used the recent medium of photography to earn a living as a merchant and tradesman. From the relative tranquility of a Minnesota photographic studio, he moved westward. And, like thousands of others, he made his way to the Klondike Gold Rush, although with camera in hand. In addition to preserving the rich photographic record of the Great Stampede to the Klondike, Larson recorded contemporary Western life and culture, including that of the hard rock mining community of Goldfield, Nevada. Frozen in Silver is a riveting story of one man's trek through a time and place that have been captured on film and now in print. (shrink)

Study on empirical reality (vyāvahārika).

Sed quid ego Graecorum: nescio quo modo me magis nostra delectant. Omnes hoc historici, Fabii Gellii sed proxume Coelius: cum bello Latino ludi votivi maxumi primum fierent, civitas ad arma repente est excitata … Quintus goes on to tell the story of the countryman's dream, with its divine warning about the ominous praesul, which is also related by Livy, Dionysius, Valerius Maximus, and Macrobius.

Asconius 63 , commenting on the pro Cornelio: Fuerunt enim plures Quinti Metelli, ex quibus duo consulares, Pius et Creticus, de quibus apparet eum non dicere, duo autem adulescentes, Nepos et Celer, ex quibus nunc Nepotem significat. Eius enim patrem Q.Metellum Nepotem, Baliarici filium, Macedonici nepotem qui consul fuit cum T. Didio, Curio is de quo loquitur accusavit … Cicero and his scholiast refer to ‘duo Metelli, Celer et Nepos’ but like Asconius do not specify their relationship. Celer himself, followed (...) by Cicero in correspondence with him, calls Nepos his frater, but since both bore the praenomen Q., this cannot be the whole story. Celer's career shows that he was the elder, yet Nepos senior, according to Asconius, entrusted his feud with Curio not to him but to Nepos iunior. (shrink)

I Should like to draw attention to two little-known inscriptions of republican senators; both men deserve notice in that each of them may illustrate the early stages of the recruitment of provincial senators, from Transpadane and Narbonese Gaul respectively.

Nothing is known of the poet Grattius except that he was a contemporary of Ovid. However, certain peculiarities in the text of hisCynegeticasuggest that he wrote for public performance, that the poem was presented atludi scaeniciwhere dancers and singers were performing too, that the Palatine temple of Apollo was probably where the event took place, and that the most likely occasion for it was one of the ‘quinquennial’ games celebrating the defeat of Cleopatra.

Some say that only 30 were seized, and that the Curiae were named after them, but Valerius Antias [fr. 3P] says there were 527, Juba [FGrH275F23] that there were 683. They were virgins, which was Romulus' main justification: no married women were taken – except one, Hersilia, by mistake - since it was not in wanton violence or injustice that they resorted to rape, but with the intention of bringing the two peoples together and uniting them with the strongest ties. (...) As for Hersilia, some say she was married to Hostilius, a very distinguished Roman, others that she was married to Romulus himself and even bore him children: one daughter, Prima, so called from the order of birth, and a single son, whom Romulus named Aollios after the crowd of citizens under his rule, though he was subsequently called Abillios [i.e. Avillius]. Many authors, however, contradict this account, which is given by Zenodotus of Troezen [FGrH 821F2]. (shrink)

The question of form and content is one of the fundamental questions of esthetics and the theory of art. However, it remains unresolved in many respects. Certain of its aspects still have not been investigated, and others have been treated only very sketchily.

Artist Leonid Filatov. Kakimi raznorodnymi talantami on odaren! YArkij kinorezhisser. Blistatel'nyj parodist. Skazochnik. I vse, chto on delal - pechal'noe i mudroe - na radost' nam. Ego poeziya sozdaet obrazy dushevnoj zhizni lyudej, nepohozhih drug na druga, dazhe protivostoyaschih drug drugu. Eto svojstvo istinnogo iskusstva. Komedijnaya p'esa po motivam bessmertnogo romana Dyuma otkryla nam esche odnu storonu ego darovanij.