1,300 research outputs found
Global science meets ethnic diversity : Ian McGonigle interviews GenomeAsia100K scientific chairman Stephan Schuster
GenomeAsia100K is a human genome project based at Nanyang Technological University in Singapore that aims to sequence one hundred thousand Asian genomes in an effort that addresses an ethnic bias towards Western populations in previous genomic research. GenomeAsia100K consists of a team of bioinformaticians, statisticians and population geneticists, and was initiated by the Nanyang Technological University in collaboration with industrial partners MedGenome (an Indian R&D company specializing in genomic data) and the California Biotech company Genentech. The GenomeAsia100K project is amongst the most ambitious precision medicine projects to date but it is not clear how the project will challenge or reshape understandings of ethnic and racial differences in Asian populations. Ian McGonigle, a scientist and cultural anthropologist, sat down with geneticist Stephan C. Schuster, the scientific chairman of GenomeAsia100K, to discuss the project and the implications of genomics for social identity in the 21st century.Published versio
Simulating Online Business Models
The online content market for news and music is changing rapidly with the spread of technology and innovative business models (e.g. the online delivery of music, specialised subscription news services). It is correspondingly hard for suppliers of online content to anticipate developments and the effects of their businesses. The paper describes a prototype multiagent simulation to model possible scenarios in this market. The simulation is intended for use by business strategists and has been developed using a participatory, rapid prototyping methodology. The implications of the method and the characteristics of the domain for the design are considered.agent-based modelling, market simulation
Medieval Russian Library (VI) : Pskovian History and Literature 1, The Story of the Siege of Pskov by Stephan Bathory
The author in this bulletin provides a translations of and a commentary on a literary work supposed to have been written in 1580’s in Pskov, a city located in the western edge of the territory of Moscovite State. The work depicts the Pskov’s heroic defiance to the assault by Stephan Bathory, king of Poland and Lithuania, at the final stage of so-called the Livonian War. The Livonian War began with the seizure of Livonia from the reign of Teutonic Knights by Ivan IV, which provoked the entry into war of the Polish-Lithuanian united kingdom and Sweden, ended by the desperate resistance of Pskov, which resulted in the armistice. The siege stood for 5 months and eventually the Moscovite State could not get the entrance to the Baltic sea. The author of this story, the Pskovian icon-painter Vasily, has a clear patriotic inclination and makes no disguise of his loyalty to Moscovian Tsar’ Ivan IV and his hostility to the enemies, particularly to Stephan Bathory, whom the author calls “savage beast”, “virulent cobra”, “eater of vomit” etc. On the other hand, he always celebrates Ivan IV, who was in fact a tyrant, as a merciful sovereign and incarnation of justice. In spite of this monochromatic characterization, the real scenery of the besieged city and its rising patriotic emotions provide artistic value to this literary work, which is one of the masterpieces of military stories of Medieval Russia.departmental bulletin pape
Changing incentives to publish
Many national governments have implemented policies providing incentives for researchers to publish, especially in highly ranked international journals. Although still the top publishing nation, the United States has seen its share of publications decline from 34.2% in 1995 to 27.6% in 2007 as the number of articles published by U.S. scientists and engineers has plateaued and that of other countries has grown (1, 2). Hicks (3) argues that the two events are not unrelated: The decline in the relative performance of the United States relates to increased international competition engendered by newly adopted incentives that have crowded out some work by U.S. author
Catalytic P-H activation by Ti and Zr catalysts
Catalytic dehydrocoupling of phosphines was investigated using the anionic zirconocene trihydride salts [Cp*Zr-2(mu-H)(3)Li](3) (1a) or [Cp*Zr-2(mu-H)(3)K(thf)(4)] (1b), and the metallocycles [CpTi(NPtBu3)(CH2)(4)] (6) and [Cp*M(NPtBu3)(CH2)(4)] (M = Ti 20, Zr 21) as catalyst precursors. Dehydrocoupling of primary phosphines RPH2 (R = Ph, C6H2Me3, Cy, C10H7) gave both dehydrocoupled dimers RP(H)P(H)R or cyclic oligophosphines (RP)(n) (n = 4, 5) while reaction of tBu(3)C(6)H(2)PH(2) gave the phosphaindoline tBu(2)(Me2CCH2)C6H2PH (9). Stoichiometric reactions of these catalyst precursors with primary phosphines afforded [Cp*Zr-2((PR)(2))H][K(thf)(4)] (R = Ph 2, Cy 3, C6H2Me3 4), [Cp*Zr-2((PPh)(3))H] [K(thf)(4)] (5), [CpTi(NPtBu3)(PPh)(3)] (7) and [CpTi(NPtBu3)(mu-PHPh)](2) (8), while reaction of 6 with (C(6)H(2)tBu3)PH2 in the presence of PMe3 afforded [CpTi(NPtBu3)(PMe3)(p(C(6)H(2)tBu(3))] (10). The secondary phosphines Ph2PH and (PhHPCH2)(2)CH2 also undergo dehydrocoupling affording (Ph2P)(2) and (PhPCH2)(2)CH2. The bisphosphines (CH2PH2)(2) and C6H4(PH2)(2) are dehydrocoupled to give (PCH2CH2PH)(2) (12) and (C6H4P(PH))(2) (13) while prolonged reaction of 13 gave (C6H4P2)(8) (14). The analogous bisphosphine Me2C6H4(PH)(2) (17) was prepared and dehydrocoupling catalysis afforded (Me2C6H2P(PH))(2) (18) and subsequently [(Me2C6H2P2)(2)(mu-Me2C6H2P2)](2) (19). Stoichiometric reactions with these bisphosphines gave [Cp*Zr-2(H)(PH)(2)C6H4] [Li(thf)(4)] (22), [Cp*Ti(NPtBu3)(PH)(2)C6H4](2) (23) and [Cp*Ti(NPtBu3)(PH)(2)C6H4] (24). 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Corresponding author
Comparison of three methods for detection of gametocytes in Melanesian children treated for uncomplicated malaria Stephan Karl 1,2,3,4*,
Diversity and distribution of Asian Lejeuneaceae subfamily Ptychanthoideae
A synopsis is provided of 88 species in 17 genera currently recognized in Lejeuneaceae subfamily Ptychanthoideae sensu lato (including Nipponolejeunea) of Asia. Taxonomic novelties include Thysananthus flavescens (Hatt.) comb. nov. (for Mastigolejeunea flavescens (Hatt.) Mizut.), Spruceanthus macrostipulus (Steph.) comb. nov. (for Archilejeunea macrostipula (Steph.) Verd.) and the reduction of Platylejeunea Mizut. to synonymy under Lopholejeunea
Recognition by forensic facial approximation: Case specific examples and empirical tests
Copyright © 2005 Elsevier Ireland Ltd All rights reserved.The skeletal remains of one individual found near Adelaide in 1994, although not known at the time, were the first evidence of what was to be a serial killing reported to have resulted in the highest casualty list to date in Australia (12 victims). Since the usual methods of identification could not be used or were unsuccessful on these remains, facial approximations were produced and advertised over the 4-year period following their discovery, in an attempt to help to identify them. However, no identification was made. In 1999, the remains were reported to be identified by radiographic comparison. Approximately 3 months before this identification was made, another facial approximation was produced by the first author (CNS), but this face was never advertised in the media. Although rarely reported in the literature, this paper provides an example where facial approximation methods were not successful in a forensic scenario. The paper also reports on empirical tests of the facial approximation created by the first author to determine if this facial approximation might have been useful had it been advertised. The results provide further evidence that high resemblance of a facial approximation to the target individual does not indicate recognizability, as the facial approximation was poorly recognized even though it bore good resemblance to the target individual. The usefulness of facial approximation techniques is discussed within the context of this case and more broadly. Methods used to assess the accuracy of facial approximations are also discussed and further evaluated.C.N. Stephan and M. Henneberghttp://www.elsevier.com/wps/find/journaldescription.cws_home/505512/description#descriptio
Cloning and functional analysis of the 5'-flanking region of the human cardiac ERα gene
Die Östrogene üben ihre Wirkung überwiegend durch die Aktivierung der
Östrogenrezeptoren ERalpha und ERbeta aus. Die Transkription des humanen
ERalpha-Gens kann von sieben verschiedenen Promotoren (A, B, C, D, E, F und T)
initiiert werden, deren Transkripte sich alle in der 5’-UTR unterscheiden.
Diese Promotoren werden zell- und gewebespezifisch exprimiert. Um die
transkriptionelle Regulation des hERalpha-Gens im humanen Myokard zu
untersuchen, wurden zunächst die alternativen 5’-UTR-Varianten des hERalpha-
Gens mittels 5’-RACE, PCR und semiquantitativer PCR identifiziert. Es konnte
gezeigt werden, dass die ERalpha-mRNA von den Promotoren A, B, C und F
transkribiert werden, von denen der F-Promotor die dominante Variante ist. Für
die funktionellen in vitro-Studien in der humanen Kardiomyozyten-Zelllinie
AC16 wurden Teilbereiche der verschiedenen Promotorsequenzen der vier
identifizierten Promotoren amplifiziert und in das pGL2-basic-Luciferase-
Reporter-Plasmid kloniert. Die transienten Transfektionsexperimente mit
Deletionskonstrukten der Promotorvariante F wiesen auf einen negativ-
regulatorischen Bereich zwischen -490 bp und -440 bp hin. Die durch
zielgerichtete Mutagenese erzeugten Mutationen innerhalb der putativen NF-
kappaB- und CDP-Bindungsstellen führten zu einer signifikanten Erhöhung der
Luciferase-Aktivität. Mittels des electrophoretic mobility shift assays (EMSA
)/Supershift-Assays und des Shift-Western konnte die Bindung des
Transkriptionsfaktors NF-kappaB p50 an die identifizierte Sequenz innerhalb
des F-Promotors des hERalpha-Gens nachgewiesen werden. Die DNA-Bindung der
Transkriptionsfaktoren p65, CDP und PHB konnte hingegen nicht eindeutig
nachgewiesen werden. Die Inhibition der NF-kappaB-Aktivität durch Parthenolid
der zuvor mit dem hERalpha-F-Promotorkonstrukt transient transfizierten
AC16-Zellen führte zu einer signifikanten Erhöhung der transkriptionellen
Aktivität des F-Promotors. Weitere Experimente ergaben, dass Parthenolid die
Translokation von NF-kappaB p50 aus dem Zytoplasma in den Nukleus verhindert
und folglich die Konzentration an NF-kappaB p50 im Nukleus signifikant
reduziert. Die immunhistochemischen Befunde weisen auf ein erhöhtes Vorkommen
an hERalpha im Nukleus und im Zytoplasma im Falle einer Inhibition der NF-
kappaB-Aktivität hin. Diese Ergebnisse deuten darauf hin, dass der NF-kappaB-
Signalweg ein Bestandteil des regulatorischen Mechanismus für die Expression
von ERalpha in humanen Kardiomyozyten ist. Darüber hinaus konnte gezeigt
werden, dass 17beta-Östradiol (E2) die transkriptionelle Aktivierung der
hERalpha-Promotoren A, B, C und F in Abhängigkeit von hERalpha bewirkt. So
können letztlich inflammatorische Stimuli durch die Aktivierung und die
anschließende Bindung von NF-kappaB an den hERalpha-F-Promotor einen
suppressorischen Einfluss auf die hERalpha-Expression besitzen und E2/hERalpha
einen antagonistischen Effekt auf die ERalpha-Promotoren im humanen Myokard
ausüben.Estrogens mediate their effects mainly through activation of the estrogen
receptors ERalpha and ERbeta. The transcription of the human ERalpha gene can
be initiated from seven different promoters (A, B, C, D, E, F and T) whose
transcripts all differ in their 5’-UTR. These promoters are expressed in a
cell- and tissue-specific manner. To investigate the transcriptional
regulation of the hERalpha gene in the human myocardium, the alternative
5’-UTR variants of the hERalpha gene were initially identified using 5’-RACE,
PCR and semiquantitative PCR. It could be shown that the ERalpha-mRNA is
transcribed from multiple promoters, namely A, B, C and F, of which the
F-promoter is the most frequently used variant. For functional in vitro
studies in the human cardiac myocyte cell line AC16, portions of the different
promoter sequences of the four identified promoters were amplified and cloned
into the pGL2-basic luciferase reporter plasmid. The transient transfection
experiments with deletion constructs of the promoter variant F exhibited a
negative regulatory region between -490 bp and -440 bp. The induced mutations
via site-directed mutagenesis within the putative NF-kappaB and CDP binding
sites led to a significant increase of the luciferase activity. Using
electrophoretic mobility shift assays (EMSA)/supershift assays and Shift-
Western, the binding of the transcription factor NF-kappaB p50 to the
identified sequence within the F-promoter of the hERalpha gene could be
verified. However, the DNA-binding of the transcription factors p65, CDP and
PHB could not be clearly identified. The inhibition of the NF-kappaB activity
by parthenolide with the prior transiently transfected hERalpha-F-promoter
construct into the AC16 cells led to a significant increase of the
transcriptional activity of the F-promoter. Further experiments showed that
parthenolide inhibits the translocation of NF-kappaB p50 out of the cytoplasm
into the nucleus, and consequently significantly decreased the concentration
of NF-kappaB p50 in the nucleus. The immunohistochemical findings point to an
increased occurrence of hERalpha in the nucleus and in the cytoplasm in the
case of inhibition of the NF-kappaB activity. These results suggest that the
NF-kappaB signalling pathway is an integral part of the regulatory mechanism
for the expression of ERalpha in human cardiomyocytes. In addition it could be
shown that 17beta-estradiol (E2) induced the transcriptional activity of the
hERalpha promoters A, B, C and F in a hERalpha dependent manner. Finally,
inflammatory stimuli may suppress hERalpha expression via activation and
subsequent binding of NF-kappaB to the hERalpha F-promoter, and E2/hERalpha
may exert an antagonistic effect on the ERalpha promoters in the human
myocardium
Competition and Antitrust Policy in the Enlarged European Union: A Level Playing Field?
With the central and eastern European countries (CEECs) increasingly included into the international division of labour in the European economic space, we are prompted to ask whether this integration operates on a level playing field with respect to competition policy. In fact, our analysis reveals that effectiveness of implementation of competition law and policy and intensity of competition are lower in the CEECs. We find no reason to believe that the new eastern EU members struggle with the recent reforms of competition policy in the EU, nor do we see the necessity for policy action to spur effective implementation. Copyright (c) 2009 The Author(s). Journal compilation (c) 2009 Blackwell Publishing Ltd.
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