The effects of airline alliances: What do the aggregate data say?

We consider an empirical model of worldwide airline alliances that we apply to a large set of companies for the period 1995-2000. Using observations at the companies level, we estimate a cost, capacity, and demand system that accounts for cross-price elasticities. From the estimates, we shed light on the fact that many airlines involved in the same alliances are potential substitutes. We also test for the effects of alliances on airlines’ fares and suggest that airlines inside alliances cut prices by 5% on average compared to airlines outside alliances. Finally, we construct price-cost margins for each airlines and suggest that current pricing habits are not uniform and vary from one alliance to another.alliances, airline, cross-price elasticities, Nash behavior

Viola primulifolia L.

https://thekeep.eiu.edu/herbarium_specimens_byname/20769/thumbnail.jp

Proof-of-concept gene editing for the murine model of inducible arginase-1 deficiency

Arginase-1 deficiency in humans is a rare genetic disorder of metabolism resulting from a loss of arginase-1, leading to impaired ureagenesis, hyperargininemia and neurological deficits. Previously, we generated a tamoxifen-inducible arginase-1 deficient mouse model harboring a deletion of Arg1 exons 7 and 8 that leads to similar biochemical defects, along with a wasting phenotype and death within two weeks. Here, we report a strategy utilizing the Clustered, Regularly Interspaced, Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system in conjunction with piggyBac technology to target and reincorporate exons 7 and 8 at the specific Arg1 locus in attempts to restore the function of arginase-1 in induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iHLCs) and macrophages in vitro. While successful gene targeted repair was achieved, minimal urea cycle function was observed in the targeted iHLCs compared to adult hepatocytes likely due to inadequate maturation of the cells. On the other hand, iPSC-derived macrophages expressed substantial amounts of "repaired" arginase. Our studies provide proof-of-concept for gene-editing at the Arg1 locus and highlight the challenges that lie ahead to restore sufficient liver-based urea cycle function in patients with urea cycle disorders

ER Stress in Diabetic Peripheral Neuropathy: A New Therapeutic Target

Significance: Diabetes and other diseases that comprise the metabolic syndrome have reached epidemic proportions. Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, affecting ?50% of diabetic patients. Characterized by chronic pain or loss of sensation, recurrent foot ulcerations, and risk for amputation, DPN is associated with significant morbidity and mortality. Mechanisms underlying DPN pathogenesis are complex and not well understood, and no effective treatments are available. Thus, an improved understanding of DPN pathogenesis is critical for the development of successful therapeutic options. Recent Advances: Recent research implicates endoplasmic reticulum (ER) stress as a novel mechanism in the onset and progression of DPN. ER stress activates the unfolded protein response (UPR), a well-orchestrated signaling cascade responsible for relieving stress and restoring normal ER function. Critical Issues: During times of extreme or chronic stress, such as that associated with diabetes, the UPR may be insufficient to alleviate ER stress, resulting in apoptosis. Here, we discuss the potential role of ER stress in DPN, as well as evidence demonstrating how ER stress intersects with pathways involved in DPN development and progression. An improved understanding of how ER stress contributes to peripheral nerve dysfunction in diabetes will provide important insight into DPN pathogenesis. Future Directions: Future studies aimed at gaining the necessary insight into ER stress in DPN pathogenesis will ultimately facilitate the development of novel therapies. Antioxid. Redox Signal. 21, 621?633.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140287/1/ars.2013.5807.pd

Superinfection by Discordant Subtypes of HIV-1 Does Not Enhance the Neutralizing Antibody Response against Autologous Virus

Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity. Thus, we investigated whether sequential plasma from these subjects superinfected with discordant HIV-1 subtypes, who exhibit broad nAbs against heterologous viruses, also neutralize their discordant early autologous viruses with increasing potency. Comparing the neutralization capacities of sequential plasma obtained before and after superinfection of 4 subjects to those of matched plasma obtained from 4 singly infected control subjects, no difference in the increase in neutralization capacity was observed between the two groups (p = 0.328). Overall, a higher increase in neutralization over time was detected in the singly infected patients (mean change in IC50 titer from first to last plasma sample: 183.4) compared to the superinfected study subjects (mean change in IC50 titer from first to last plasma sample: 66.5). Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234). These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients

Memory-unit design for real-time-digital-signal-processing applications

The increase in the complexity of signal processing and image algorithms, under the execution time constraint, and taking into consideration the new constraints (area, speed, consumption etc .), makes exploration space a manually unachievable concept . The framework development for design became a necessity at that time, so as to offer estimation tools and semi-automatic synthesis to the designer, allowing the design of different parts of the application . In the last decade, scheduling and resources allocation algorithms (operators, registers etc .) have given rise to a number of synthesis tools of a high level for the designing of operative and control parts . However, if these tools allow the designing of these two units in a more or less automatic way, then it is not the same for the memorisation unit which should, most of the time, be explicitly designed . The evolution of applications, notably in signal processing, applies itself, not only to the operative system part, but also and above all, to the memorisation ; this last point can rapidly become the critical point in the implementation .L'augmentation de complexité des algorithmes de traitement du signal et de l'image, sous contrainte de temps d'exécution, et la prise en compte de nouvelles contraintes (surface, vitesse, consommation, etc) rend l'exploration de l'espace de conception irréalisable de manière manuelle. Le développement de plates-formes de conception est alors devenu une nécessité afin d'offrir aux concepteurs des outils d'estimation et de synthèse semi-automatique permettant de concevoir les différentes parties d'une application. Dans la dernière décennie, les méthodes d'ordonnancement et d'assignation des ressources (opérateurs, registres, ...etc) ont donné naissance à de nombreux outils de synthèse de haut niveau pour la conception des parties opérative et de contrôle. Toutefois, si ces outils permettent de concevoir de manière plus ou moins automatique ces deux unités, il n'en est pas de même pour l'unité de mémorisation qui doit, la plupart du temps, être conçue explicitement. L'évolution des applications, notamment dans le domaine du traitement du signal, s'applique non seulement à la partie opérative du système, mais aussi et surtout à la mémorisation; cette dernière pouvant rapidement devenir le point critique de la mise en œuvre. Ce papier présente une méthodologie de conception de ces unités. Partant d'une description des besoins en terme de mémorisation, nous décomposons la synthèse des mémoires en quatre étapes. Cette synthèse vient alors compléter le flot de conception d'un outil de synthèse d'architectures (par exemple de l'outil Gaut)

Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma

Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise