Selling and Leasing Software with Network Externality

Previous studies suggested that a monopoly durable goods seller can use leasing to effectively avoid the time-inconsistent problem raised by Coase Conjecture. This paper extends those previous works by examining the monopoly seller's selling and leasing strategy for a special type of durable good --- software. We look at a software vendor that can sell (at a posted price) or lease his product where as a lesser he guarantees that the lessees will always have the latest version of the software. We address some of the specific issues of implementing the selling and/or leasing policies at the packaged software market, including the impact of network externality, upgrade compatibility, and commitment on pricing in a dynamic environment. We show that by properly defining their pricing structure, software vendors can segment the market and second-degree price discriminate the consumers. We also demonstrate how software vendors can manage the trade-offs of selling and leasing to achieve a higher profit as well as the corresponding welfare effect on the consumers

Genome-wide association study in two cohorts from a multi-generational mouse advanced intercross line highlights the difficulty of replication due to study-specific heterogeneity

There has been extensive discussion of the Replication Crisis in many fields, including genome-wide association studies

Clustering of Very Red Galaxies in the Las Campanas IR Survey

We report results from the first 1000 square arc-minutes of the Las Campanas IR survey. We have imaged 1 square degree of high latitude sky in six distinct fields to a 5-sigma H-band depth of 20.5 (Vega). Optical imaging in the V,R,I,and z' bands allow us to select color subsets and photometric-redshift-defined shells. We show that the angular clustering of faint red galaxies (18 3) is an order of magnitude stronger than that of the complete H-selected field sample. We employ three approaches to estimate $n(z)$ in order to invert w(theta) to derive r_0. We find that our n(z) is well described by a Gaussian with = 1.2, sigma(z) = 0.15. From this we derive a value for r_0 of 7 (+2,-1) co-moving H^{-1} Mpc at = 1.2. This is a factor of ~ 2 larger than the clustering length for Lyman break galaxies and is similar to the expectation for early type galaxies at this epoch.Comment: 5 pages, 2 figures, 1 table. To appear in proceedings of the ESO/ECF/STScI workshop "Deep Fields" held in Garching, Germany, 9-12 October 200

AKT regulates NPM dependent ARF localization and p53mut stability in tumors

Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project

Needs of caregivers in heart failure management: A qualitative study

This is a freely-available open access publication. The final version of this paper has been published in Chronic Illness, March 2015 by SAGE Publications Ltd, All rights reserved. It is available via the DOI in this record.Objectives: To identify the needs of caregivers supporting a person with heart failure and to inform the development of a caregiver resource to be used as part of a home-based selfmanagement programme. Methods: A qualitative study informed by thematic analysis involving 26 caregivers in individual interviews or a focus group. Results: Three distinct aspects of caregiver support in heart failure management were identified. Firstly, caregivers identified needs about supporting management of heart failure including: coping with the variability of heart failure symptoms, what to do in an emergency, understanding and managing medicines, providing emotional support, promoting exercise and physical activity, providing personal care, living with a cardiac device and supporting depression management. Secondly, as they make the transition to becoming a caregiver, they need to develop skills to undertake difficult discussions about the role; communicate with health professionals; manage their own mental health, well-being and sleep; and manage home and work. Thirdly, caregivers require skills to engage social support, and voluntary and formal services while recognising that the longterm future is uncertain. Discussion: The identification of the needs of caregiver has been used to inform the development of a home-based heart failure intervention facilitated by a trained health care practitioner.NIHR (Programme Grants for Applied Research