Regional Strategies of Multinational Pharmaceutical Firms

This paper examines the R&D and strategies of the world’s largest firms in the pharmaceuticals sector and finds a high degree of intra-regional sales. R&D and sales are more concentrated within North America and Europe than in Asia. In addition, the relative size of the U.S. market, compared to other parts of the triad, creates imbalances with respect to R&D, sales and international strategy.

The ‘Little Ice Age’ in the Southern Hemisphere in the context of the last 3000 years : Peat-based proxy-climate data from Tierra del Fuego

DM’s research (at Department of Earth Sciences, Uppsala University) was supported through a European Community Marie Curie Fellowship (Contract HPMF-CT-2000-01056).Peer reviewedPostprin

The ADHM Construction of Instantons on Noncommutative Spaces

We present an account of the ADHM construction of instantons on Euclidean space-time $\mathbb{R}^4$ from the point of view of noncommutative geometry. We recall the main ingredients of the classical construction in a coordinate algebra format, which we then deform using a cocycle twisting procedure to obtain a method for constructing families of instantons on noncommutative space-time, parameterised by solutions to an appropriate set of ADHM equations. We illustrate the noncommutative construction in two special cases: the Moyal-Groenewold plane $\mathbb{R}^4_\hbar$ and the Connes-Landi plane $\mathbb{R}^4_\theta$.Comment: Latex, 40 page

Anterior Olfactory Nucleus

This report contains a gene expression summary of the anterior olfactory nucleus (AON), derived from the Allen Brain Atlas (ABA) in situ hybridization mouse data set. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the AON were compared to the values of the macro/parent-structure, in this case the olfactory areas, for the purpose of extracting regionally selective gene expression data. The genes with the highest ranking selectivity ratios were manually curated and verified. 50 genes were then selected and compiled for expression characterization. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. Correlations between gene expression in the AON and the rest of the brain, across all genes in the coronal dataset (~4300 genes), were derived computationally. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report

Cerebellar Cortex, Purkinje Cell Layer

This report contains a summary of expression patterns for genes that are enriched in the Purkinje cell layer (CBXpu) of the cerebellum. All data is derived from the Allen Brain Atlas (ABA) in situ hybridization mouse project. The structure's location and morphological characteristics in the mouse brain are described using the Nissl data found in the Allen Reference Atlas. Using an established algorithm, the expression values of the CBXpu were compared to the values of its larger parent structure, in this case the cerebellar cortex, for the purpose of extracting regionally selective gene expression data. The highest ranking genes were manually curated and verified. 50 genes were then selected and compiled for expression analysis. The experimental data for each gene may be accessed via the links provided; additional data in the sagittal plane may also be accessed using the ABA. A gene ontology table (derived from DAVID Bioinformatics Resources 2007) is also included, highlighting possible functions of the 50 genes selected for this report. 
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Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia

Objective: Familial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency. Design: Mutational analysis of MC2R by direct sequencing. Patients: Children (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1). Results: MC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time. Conclusions: MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosi

Simulated kinetic effects of the corona and solar cycle on high altitude ion transport at Mars

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99008/1/jgra50358.pd

Invertibility Conditions for Floating-Point Formulae

Automated reasoning procedures are essential for a number of applications that involve bit-exact floating-point computations. This paper presents conditions that characterize when a variable in a floating-point constraint has a solution, which we call invertibility conditions. We describe a novel workflow that combines human interaction and a syntax-guided synthesis (SyGuS) solver that was used for discovering these conditions. We verify our conditions for several floating-point formats. One implication of this result is that a fragment of floating-point arithmetic admits compact quantifier elimination. We implement our invertibility conditions in a prototype extension of our solver CVC4, showing their usefulness for solving quantified constraints over floating-points

Learning from the past with experiment databases

Thousands of Machine Learning research papers contain experimental comparisons that usually have been conducted with a single focus of interest, and detailed results are usually lost after publication. Once past experiments are collected in experiment databases they allow for additional and possibly much broader investigation. In this paper, we show how to use such a repository to answer various interesting research questions about learning algorithms and to verify a number of recent studies. Alongside performing elaborate comparisons and rankings of algorithms, we also investigate the effects of algorithm parameters and data properties, and study the learning curves and bias-variance profiles of algorithms to gain deeper insights into their behavior