1,758 research outputs found
Linkage Evidence for a Two-Locus Inheritance of LQT-Associated Seizures in a Multigenerational LQT Family With a Novel KCNQ1 Loss-of-Function Mutation
Mutations in several genes encoding ion channels can cause the long-QT (LQT)
syndrome with cardiac arrhythmias, syncope and sudden death. Recently, mutations in
some of these genes were also identified to cause epileptic seizures in these patients, and
the sudden unexplained death in epilepsy (SUDEP) was considered to be the pathologic
overlap between the two clinical conditions. For LQT-associated KCNQ1 mutations, only
few investigations reported the coincidence of cardiac dysfunction and epileptic seizures.
Clinical, electrophysiological and genetic characterization of a large pedigree (n = 241
family members) with LQT syndrome caused by a 12-base-pair duplication in exon 8 of
the KCNQ1 gene duplicating four amino acids in the carboxyterminal KCNQ1 domain
(KCNQ1dup12; p.R360_Q361dupQKQR, NM_000218.2, hg19). Electrophysiological
recordings revealed no substantial KCNQ1-like currents. The mutation did not exhibit a
dominant negative effect on wild-type KCNQ1 channel function. Most likely, the mutant
protein was not functionally expressed and thus not incorporated into a heteromeric
channel tetramer. Many LQT family members suffered from syncopes or developed
sudden death, often after physical activity. Of 26 family members with LQT, seizures were
present in 14 (LQTplus seizure trait). Molecular genetic analyses confirmed a causative
role of the novel KCNQ1dup12 mutation for the LQT trait and revealed a strong link
also with the LQTplus seizure trait. Genome-wide parametric multipoint linkage analyses
identified a second strong genetic modifier locus for the LQTplus seizure trait in the
chromosomal region 10p14. The linkage results suggest a two-locus inheritance model
for the LQTplus seizure trait in which both the KCNQ1dup12 mutation and the 10p14
risk haplotype are necessary for the occurrence of LQT-associated seizures. The data
strongly support emerging concepts that KCNQ1 mutations may increase the risk of
epilepsy, but additional genetic modifiers are necessary for the clinical manifestation of
epileptic seizures
Настройка моделей при создании систем поддержки принятия стратегических решений
Показана актуальность разработки платформы (программной среды), позволяющей на её основе создавать системы стратегического управления организациями, используя сквозные технологии поддержки принятия решений и универсальные инструментальные средства. Статья посвящена решению одной из задач, возникающей при разработке такой платформы - настройке универсальных моделей поддержки принятия решений под условия принятия решений и особенности предметной области стратегического управления. Разработан механизм настройки моделей, выявлены и представлены параметры настройки
RKKY interaction and Kondo screening cloud for correlated electrons
The RKKY law and the Kondo screening cloud around a magnetic impurity are
investigated for correlated electrons in 1D (Luttinger liquid). We find slow
algebraic distance dependences, with a crossover between both types of
behavior. Monte Carlo simulations have been developed to study this crossover.
In the strong coupling regime, the Knight shift is shown to increase with
distance due to correlations.Comment: 5 pages REVTeX, incl two figures, to appear in Phys.Rev.
How Preussag became TUI : kissing too many toads can make you a toad
In the period 1997-2004, Preussag, a diversified German conglomerate of old economy businesses, changed itself into TUI, a company focused almost entirely on tourism and logistics. This paper analyzes how this strategy was executed and how it contributed to Preussag’s underperformance of the stock market. We collect 417 announcements of acquisitions, financial disclosures and other news and disentangle the impact of different parts of the company’s strategy. We find that only the divestitures created value, that the strategy to invest in tourism destroyed value, and that the acquisition premiums Preussag paid were mostly unjustified. Bad luck like the events of September 11, 2001 cannot account for the poor performance of the stock. Poor management resulted from poor governance, combining a state-owned bank as the largest shareholder, board interlocks, and insufficient managerial incentives. The case shows how divestiture programs increase the liquid resources available to management beyond free operating cash flows and casts doubt on the positive governance role of institutional blockholders
Sea surface temperatures of the western Arabian Sea during the last deglaciation.
In this study we present a sea surface temperature (SST) record from the western Arabian Sea for the last\ud
20,000 years. We produced centennial-scale d18O and Mg/Ca SST time series of core NIOP929 with focus on\ud
the glacial-interglacial transition. The western Arabian Sea is influenced by the seasonal NE and SW monsoon\ud
wind systems. Lowest SSTs occur during the SW monsoon season because of upwelling of cold water, and\ud
highest SSTs can be found in the low-productivity intermonsoon season. The Mg/Ca-based temperature record\ud
reflects the integrated SST of the SW and NE monsoon seasons. The results show a glacial-interglacial SST\ud
difference of 2C, which is corroborated by findings from other Arabian Sea cores. At 19 ka B.P. a yet\ud
undescribed warm event of several hundred years duration is found, which is also reflected in the d18O record. A\ud
second centennial-scale high SST/low d18O event is observed at 17 ka B.P. This event forms the onset of the\ud
stepwise yet persistent trend toward Holocene temperatures. Highest Mg/Ca-derived SSTs in the NIOP929\ud
record occurred between 13 and 10 ka B.P. Interglacial SST is 24C, indicating influence of upwelling. The\ud
onset of Arabian Sea warming occurs when the North Atlantic is experiencing minimum temperatures. The rapid\ud
temperature variations at 19, 17, and 13 ka B.P. are difficult to explain with monsoon changes alone and are\ud
most likely also linked to regional hydrographic changes, such as trade wind induced variations in warm water\ud
advection
“Excellence R Us”: university research and the fetishisation of excellence
The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship
Factor structure and psychometric properties of the english version of the trier inventory for chronic stress (TICS-E)
Erratum to: The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies
Effect of glenoid concavity loss on shoulder stability- a case report in a professional wrestler
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