260 research outputs found

    Twisted Conjugacy Classes in Lattices in Semisimple Lie Groups

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    Given a group automorphism ϕ:ΓΓ\phi:\Gamma\to \Gamma, one has an action of Γ\Gamma on itself by ϕ\phi-twisted conjugacy, namely, g.x=gxϕ(g1)g.x=gx\phi(g^{-1}). The orbits of this action are called ϕ\phi-conjugacy classes. One says that Γ\Gamma has the RR_\infty-property if there are infinitely many ϕ\phi-conjugacy classes for every automorphism ϕ\phi of Γ\Gamma. In this paper we show that any irreducible lattice in a connected semi simple Lie group having finite centre and rank at least 2 has the RR_\infty-property.Comment: 6 page

    The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking

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    Heat shock protein 90 (Hsp90) has emerged as a promising therapeutic target for the treatment of cancer. Several Hsp90 inhibitors have entered clinical trials. However, some toxicological detriments have arisen, such as cardiotoxicity resulting from hERG inhibition following the administration of Hsp90 inhibitors. We sought to investigate this toxicity as hERG has been previously reported as a client protein that depends upon Hsp90 for its maturation and functional trafficking. In this study we show that hERG depends upon a single Hsp90 isoform. hERG preferentially co-immunoprecipitated with Hsp90α and genetic knockdown of Hsp90α, but not Hsp90β, resulted in a trafficking-defective hERG channel. This study demonstrates the importance of delineating the isoform dependence of Hsp90 client proteins and provides rationale for the design of isoform-selective Hsp90 inhibitors that avoid detrimental effect

    Gaudin Models and Bending Flows: a Geometrical Point of View

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    In this paper we discuss the bihamiltonian formulation of the (rational XXX) Gaudin models of spin-spin interaction, generalized to the case of sl(r)-valued spins. In particular, we focus on the homogeneous models. We find a pencil of Poisson brackets that recursively define a complete set of integrals of the motion, alternative to the set of integrals associated with the 'standard' Lax representation of the Gaudin model. These integrals, in the case of su(2), coincide wih the Hamiltonians of the 'bending flows' in the moduli space of polygons in Euclidean space introduced by Kapovich and Millson. We finally address the problem of separability of these flows and explicitly find separation coordinates and separation relations for the r=2 case.Comment: 27 pages, LaTeX with amsmath and amssym

    Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

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    Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate

    Global Health Governance and the Commercial Sector: A Documentary Analysis of Tobacco Company Strategies to Influence the WHO Framework Convention on Tobacco Control

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    Heide Weishaar and colleagues did an analysis of internal tobacco industry documents together with other data and describe the industry's strategic response to the proposed World Health Organization Framework Convention on Tobacco Control

    Somatic health among heroin addicts before and during opioid maintenance treatment: a retrospective cohort study

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    <p>Abstract</p> <p>Background</p> <p>The long-term impact of opioid maintenance treatment (OMT) on morbidity and health care utilization among heroin addicts has been insufficiently studied. The objective of this study was to investigate whether health care utilization due to somatic disease decreased during OMT, and if so, whether the reduction included all kinds of diseases and whether a reduction was related to abstinence from drug use.</p> <p>Methods</p> <p>Cohort study with retrospective registration of somatic disease incidents (health problems, acute or sub-acute, or acute problems related to chronic disease, resulting in a health care contact). Medical record data were collected from hospitals, Outpatients' Departments, emergency wards and from general practitioners (GPs) and prospective data on substance use during OMT were available from 2001 onwards. The observation period was five years before and up to five years during OMT. The cohort consisted of 35 out of 40 patients who received OMT between April 1999 and January 2005 in a Norwegian district town. Statistical significance concerning changes in number of incidents and inpatient and outpatient days during OMT compared with the pre OMT period was calculated according to Wilcoxon signed rank test. Significance concerning pre/during OMT changes in disease incidents by relation to the type of health service contacts, as well as the impact of ongoing substance use during OMT on the volume of contacts, was calculated according to Pearson chi-square and Fisher's exact tests.</p> <p>Results</p> <p>278 disease incidents were registered. There was a reduction in all incidents by 35% (p = 0.004), in substance-related incidents by 62% (p < 0.001) and in injection-related incidents by 70% (p < 0.001). There was an insignificant reduction in non-fatal overdose incidents by 44% (p = 0.127) and an insignificant increase in non-substance-related incidents by 13% (p = 0.741). Inpatient and outpatient days were reduced by 76% (p = 0.003) and 46% (p = 0.060), respectively. The disease incidents were less often drug-related during OMT (p < 0.001). Patients experienced a reduction in substance-related disease incidents regardless of ongoing substance use, however there was a trend towards greater reductions in those without ongoing abuse.</p> <p>Conclusion</p> <p>Although as few as 35 patients were included, this study demonstrates a significant reduction in health care utilization due to somatic disease incidents during OMT. The reduction was most pronounced for incidents related to substance use and injection. Inpatient and outpatient days were reduced. Most probably these findings reflect somatic health improvement among heroin addicts during OMT.</p

    Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

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    Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD
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