Geometry acquisition and grid generation: Recent experiences with complex aircraft configurations

Important issues involved in working with complex geometries are discussed. Approaches taken to address complex geometry issues in the McDonnell Aircraft Computational Grid System and related geometry processing tools are discussed. The efficiency of acquiring a suitable geometry definition, the need to manipulate the geometry, and the time and skill level required to generate the grid while preserving geometric fidelity are discussed

Dediščina izjemnih osebnosti kot potencial za razvoj kulturnega turizma v Romuniji

This article investigates how domestic tourists perceive the possibilities of boosting cultural heritage tourism in Romania, through the capitalization of national genius personalities. The methodology is based on the survey method. The research identified 22 geniuses, largely represented in national culture, and acknowledged and demanded by the market. The vast majority have been converted into tourist attractions, however those of international visibility are missing or are underrepresented in Romanian heritage tourism. An increased focus on geniuses would be highly valued by tourists and could reinforce the value of cultural heritage, consequently, boosting tourism resources. This would lead to multiple and sustainable benefits for destinations’ development, but certain infrastructure and management gaps would need to be filled.Avtorji v članku proučujejo mnenja domačih turistov o možnostih spodbujanja razvoja kulturnega turizma v Romuniji na podlagi izjemnih osebnosti iz romunske kulturne zgodovine. Uporabljena metodologija temelji na anketi, v kateri so vprašani izpostavili 22 romunskih kulturnih osebnosti, prepoznanih na trgu. Večina je bila preobražena v turistične zanimivosti, pri čemer pa v romunskem dediščinskem turizmu manjkajo mednarodno prepoznavne osebnosti ali so te slabo zastopane. Večji poudarek na tovrstnih osebnostih bi turisti zelo dobro sprejeli, hkrati bi se s tem povečala vrednost kulturne dediščine, kar bi posledično spodbudilo razvoj novih turističnih virov. Navedeno bi imelo različne trajnostne koristi za razvoj destinacij, treba pa bi bilo zapolniti nekatere vrzeli v infrastrukturi in upravljanju

Empirical Evidence on Inflation and Unemployment in the Long Run

We examine the relationship between inflation and unemployment in the long run, using quarterly US data from 1952 to 2010. Using a band-pass filter approach, we find strong evidence that a positive relationship exists, where inflation leads unemployment by some 3 to 3 1/2 years, in cycles that last from 8 to 25 or 50 years. Our statistical approach is atheoretical in nature, but provides evidence in accordance with the predictions of Friedman (1977) and the recent New Monetarist model of Berentsen, Menzio, and Wright (2011): the relationship between inflation and unemployment is positive in the long run

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study

Patients with cancer and HIV are an underserved population. Paclitaxel and carboplatin is an active regimen against a variety of solid tumors, including several seen in excess in patients with HIV infection. This pilot trial evaluated the safety of full dose paclitaxel and carboplatin in people living with HIV and cancer

Boletín del Servicio Meteorológico Español: Año XXXV Número 148 - 1927 Mayo 28

Imbalances in endoplasmic reticulum (ER) proteostasis are associated with etiologically-diverse degenerative diseases linked to excessive extracellular protein misfolding and aggregation. Reprogramming of the ER proteostasis environment through genetic activation of the Unfolded Protein Response (UPR)-associated transcription factor ATF6 attenuates secretion and extracellular aggregation of amyloidogenic proteins. Here, we employed a screening approach that included complementary arm-specific UPR reporters and medium-throughput transcriptional profiling to identify non-toxic small molecules that phenocopy the ATF6-mediated reprogramming of the ER proteostasis environment. The ER reprogramming afforded by our molecules requires activation of endogenous ATF6 and occurs independent of global ER stress. Furthermore, our molecules phenocopy the ability of genetic ATF6 activation to selectively reduce secretion and extracellular aggregation of amyloidogenic proteins. These results show that small molecule-dependent ER reprogramming, achieved through preferential activation of the ATF6 transcriptional program, is a promising strategy to ameliorate imbalances in ER function associated with degenerative protein aggregation diseases