Delayed purchase options in single-leg revenue management

Many airline reservation systems offer the commitment option to their potential passengers. This option allows passengers to reserve a seat for a fixed duration before making a final purchase decision. In this study, we develop single-leg revenue management models that consider such contingent commitment decisions. We start with a dynamic programming model of this problem. This model is computationally intractable as it requires storing a multidimensional state space because of bookkeeping of the committed seats. To alleviate this difficulty, we propose an alternate dynamic programming formulation that uses an approximate model of how the contingent commitments behave and we show how to extract a capacity allocation policy from the approximate dynamic programming formulation. In addition, we present a deterministic linear programming model that gives an upper bound on the optimal expected revenue from the intractable dynamic programming model. As the problem size becomes large in terms of flight capacity and the expected number of arrivals, we demonstrate an asymptotic lower bound for the deterministic linear programming model. Our extensive numerical study indicates that offering commitment options can noticeably increase potential revenue even though offering a contingent commitment option may not always be in the best interest of the airline. Also, our results show that the proposed approximate dynamic programming model coordinates capacity allocation and commitment decisions quite well

MEFV mutations in systemic JIA

Background: Systemic form of juvenile idiopathic arthritis (JIA) is regarded as an autoinflammatory disease. Certain genetic polymorphisms in genes coding inflammatory proteins have been associated with the disease. On the other hand mutations of the MEFV gene cause a monogenic autoinflammatory disease, Familial Mediterranean Fever (FMF). In a previous study in adult rheumatoid arthritis 3 out of the 25 British patients who developed secondary amyloidosis had a mutation/polymorphism in the MEFV gene. Aim: To analyse whether mutaions in the MEFV gene had an association with systemic JIA. Patients and methods: MEFV mutations were screened in a total of 32 systemic JIA patients. All had been classified as systemic JIA according to the Durban JIA criteria. None had disease characteristics that met the Tel Hashomer criteria for the diagnosis of FMF. Results: 2 carrier for M694V and two patients who were homozygote for MEFV mutations. Both of these patients were among the most severe patients in the group. One had an excellent response to etanercept whereas the other was resistant to anti-TNF and other conventional treatments and had only a partial response to thalidomide. Although the number of severe mutations were increased in this small group of patients with systemic JIA the difference with the Turkish population did not reach statistical significance, but the disease causing mutation (M694V) was significantly high in the patients with systemic JIA(p = 0.02). Conclusion: However, the severe disease course in the aforementioned patients suggest that MEFV mutations may be a modifying genetic factor in systemic JIA.PubMe

IDENTIFYING EFFECTIVE POLICIES IN APPROXIMATE DYNAMIC PROGRAMMING: BEYOND REGRESSION

ABSTRACT Dynamic programming formulations may be used to solve for optimal policies in Markov decision processes. Due to computational complexity dynamic programs must often be solved approximately. We consider the case of a tunable approximation architecture used in lieu of computing true value functions. The standard methodology advocates tuning the approximation architecture via sample path information and regression to get a good fit to the true value function. We provide an example which shows that this approach may unnecessarily lead to poorly performing policies and suggest direct search methods to find better performing value function approximations. We illustrate this concept with an application from ambulance redeployment

Does unity of Familial Mediterranean fever with juvenile idiopathic arthritis affect the outcome?

PubMe

Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion

Cataloged from PDF version of article.Cerebellar ataxia, mental retardation and dysequilibrium syndrome is a rare and heterogeneous condition. We investigated a consanguineous family from Turkey with four affected individuals exhibiting the condition. Homozygosity mapping revealed that several shared homozygous regions, including chromosome 13q12. Targeted next-generation sequencing of an affected individual followed by segregation analysis, population screening and prediction approaches revealed a novel missense variant, p.I376M, in ATP8A2. The mutation lies in a highly conserved C-terminal transmembrane region of E1 E2 ATPase domain. The ATP8A2 gene is mainly expressed in brain and development, in particular cerebellum. Interestingly, an unrelated individual has been identified, in whom mental retardation and severe hypotonia is associated with a de novo t(10;13) balanced translocation resulting with the disruption of ATP8A2. These findings suggest that ATP8A2 is involved in the development of the cerebro-cerebellar structures required for posture and gait in humans. © 2013 Macmillan Publishers Limited All rights reserved

Epitope tagging of endogenous genes in diverse human cell lines

Epitope tagging is a powerful and commonly used approach for studying the physical properties of proteins and their functions and localization in eukaryotic cells. In the case of Saccharomyces cerevisiae, it has been possible to exploit the high efficiency of homologous recombination to tag proteins by modifying their endogenous genes, making it possible to tag virtually every endogenous gene and perform genome-wide proteomics experiments. However, due to the relative inefficiency of homologous recombination in cultured human cells, epitope-tagging approaches have been limited to ectopically expressed transgenes, with the attendant limitations of their nonphysiological transcriptional regulation and levels of expression. To overcome this limitation, a modification and extension of adeno-associated virus-mediated human somatic cell gene targeting technology is described that makes it possible to simply and easily create an endogenous epitope tag in the same way that it is possible to knock out a gene. Using this approach, we have created and validated human cell lines with epitope-tagged alleles of two cancer-related genes in a variety of untransformed and transformed human cell lines. This straightforward approach makes it possible to study the physical and biological properties of endogenous proteins in human cells without the need for specialized antibodies for individual proteins of interest