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Showing papers by "Uppsala University published in 2007"


Journal ArticleDOI
14 Jun 2007-Nature
TL;DR: Functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project are reported, providing convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts.
Abstract: We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.

5,091 citations


Journal ArticleDOI
TL;DR: In this paper, the role of inland water ecosystems in the global carbon cycle has been investigated and it is shown that roughly twice as much C enters inland aquatic systems from land as is exported from land to the sea, roughly equally as inorganic and organic carbon.
Abstract: Because freshwater covers such a small fraction of the Earth’s surface area, inland freshwater ecosystems (particularly lakes, rivers, and reservoirs) have rarely been considered as potentially important quantitative components of the carbon cycle at either global or regional scales. By taking published estimates of gas exchange, sediment accumulation, and carbon transport for a variety of aquatic systems, we have constructed a budget for the role of inland water ecosystems in the global carbon cycle. Our analysis conservatively estimates that inland waters annually receive, from a combination of background and anthropogenically altered sources, on the order of 1.9 Pg C y−1 from the terrestrial landscape, of which about 0.2 is buried in aquatic sediments, at least 0.8 (possibly much more) is returned to the atmosphere as gas exchange while the remaining 0.9 Pg y−1 is delivered to the oceans, roughly equally as inorganic and organic carbon. Thus, roughly twice as much C enters inland aquatic systems from land as is exported from land to the sea. Over prolonged time net carbon fluxes in aquatic systems tend to be greater per unit area than in much of the surrounding land. Although their area is small, these freshwater aquatic systems can affect regional C balances. Further, the inclusion of inland, freshwater ecosystems provides useful insight about the storage, oxidation and transport of terrestrial C, and may warrant a revision of how the modern net C sink on land is described.

3,179 citations


Journal ArticleDOI
TL;DR: It is shown that the waveform diversity offered by such a MIMO radar system enables significant superiority over its phased-array counterpart, including much improved parameter identifiability, direct applicability of adaptive techniques for parameter estimation, as well as superior flexibility of transmit beampattern designs.
Abstract: We have provided a review of some recent results on the emerging technology of MIMO radar with colocated antennas. We have shown that the waveform diversity offered by such a MIMO radar system enables significant superiority over its phased-array counterpart, including much improved parameter identifiability, direct applicability of adaptive techniques for parameter estimation, as well as superior flexibility of transmit beampattern designs. We hope that this overview of our recent results on the MIMO radar, along with the related results obtained by our colleagues, will stimulate the interest deserved by this topic in both academia and government agencies as well as industry.

2,163 citations


Journal ArticleDOI
TL;DR: A comprehensive phylogenetic classification of the kingdom Fungi is proposed, with reference to recent molecular phylogenetic analyses, and with input from diverse members of the fungal taxonomic community.

2,096 citations


Journal ArticleDOI
Andrew G. Clark1, Michael B. Eisen2, Michael B. Eisen3, Douglas Smith  +426 moreInstitutions (70)
08 Nov 2007-Nature
TL;DR: These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution.
Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

2,057 citations


Journal ArticleDOI
TL;DR: Transparent conductors (TCs) have a multitude of applications for solar energy utilization and for energy savings, especially in buildings as discussed by the authors, which leads naturally to considerations of spectral selectivity, angular selectivity, and temporal variability of TCs, as covered in three subsequent sections.

1,471 citations


Journal ArticleDOI
TL;DR: The estimated total number of symptomatic VTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715; almost three-quarters of all VTE-related deaths were from hospital-acquired VTE.
Abstract: Venous thromboembolism (VTE) is often asymptomatic, mis-diagnosed, and unrecognized at death, and there is a lack of routine postmortem examinations. These factors are thought to result in marked underestimates ofVTE incidence. The objective of our study was to estimate the total burden of VTE within the European Union (EU) per annum. An epidemiological model was constructed to estimate the number of community- and hospital-acquired incidents and recurrent cases (attack rate) of nonfatal VTE and VTE-related deaths, as well as incident and prevalent cases of post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (PH) occurring in the EU per annum. Individual models were developed for six EU countries. The models were populated with data from published literature and, where necessary, expert opinions. The findings were tested using probabilistic sensitivity analyses. The estimated total number of symptomaticVTE events (range based on probabilistic sensitivity analysis) per annum within the six EU countries was 465,715 (404,664-538,189) cases of deep-vein thrombosis, 295,982 (242,450-360,363) cases of pulmonary embolism (PE), and 370,012 (300,193-483,108) VTE-related deaths. Of these deaths, an estimated 27,473 (7%) were diagnosed as being antemortem; 126,145 (34%) were sudden fatal PE, and 217,394 (59%) followed undiagnosed PE. Almost three-quarters of all VTE-related deaths were from hospital-acquired VTE. VTE is a major health problem in the EU, with over one million VTE events or deaths per annum in the six countries examined. Given the availability of effective VTE prophylaxis, many of these events and deaths could have been prevented. These results have important implications for the allocation of healthcare resources.

1,287 citations


Journal ArticleDOI
TL;DR: A critical review on the production of poly(lactic acid) fiber by various methods, along with correlations between structure and properties of the fibers is presented in this paper, where applications of these fibers in various domains are also discussed.

1,156 citations


Journal ArticleDOI
TL;DR: In this paper, a conceptual model for structural characteristics of amorphous W oxide films, based on notions of defects in the ideal ammorphous state, is given for thin film deposition by sputtering, electronic band structure and ion diffusion.
Abstract: Electrochromic (EC) materials are able to change their optical properties, reversibly and persistently, by the application of an electrical voltage. These materials can be integrated in multilayer devices capable of modulating the optical transmittance between widely separated extrema. We first review the recent literature on inorganic EC materials and point out that today's research is focused on tungsten oxide (colouring under charge insertion) and nickel oxide (colouring under charge extraction). The properties of thin films of these materials are then discussed in detail with foci on recent results from two comprehensive investigations in the authors' laboratory. A logical exposition is obtained by covering, in sequence, structural features, thin film deposition (by sputtering), electronic band structure, and ion diffusion. A novel conceptual model is given for structural characteristics of amorphous W oxide films, based on notions of defects in the ideal amorphous state. It is also shown that the conduction band density of states is obtainable from simple electrochemical chronopotentiometry. Ion intercalation causes the charge-compensating electrons to enter localized states, implying that the optical absorption underlying the electrochromism can be described as ensuing from transitions between occupied and empty localized conduction band states. A fully quantitative theory of such transitions is not available, but the optical absorption can be modeled more phenomenologically as due to a superposition of transitions between different charge states of the W ions (6+, 5+, and 4+). The Ni oxide films were found to have a porous structure comprised of small grains. The data are consistent with EC coloration being a surface phenomenon, most likely confined to the outer parts of the grains. Initial electrochemical cycling was found to transform hydrated Ni oxide into hydroxide and oxy-hydroxide phases on the grain surfaces. Electrochromism in thus stabilized films is consistent with reversible changes between Ni hydroxide and oxy-hydroxide, in accordance with the Bode reaction scheme. An extension of this model is put forward to account for changes of NiO to Ni2O3. It was demonstrated that electrochromism is associated solely with proton transfer. Data on chemical diffusion coefficients are interpreted for polycrystalline W oxide and Ni oxide in terms of the lattice gas model with interaction. The later part of this review is of a more technological and applications oriented character and is based on the fact that EC devices with large optical modulation can be accomplished essentially by connecting W-oxide-based and Ni-oxide-based films through a layer serving as a pure ion conductor. Specifically, we treat methods to enhance the bleached-state transmittance by mixing the Ni oxide with other oxides characterized by wide band gaps, and we also discuss pre-assembly charge insertion and extraction by facile gas treatments of the films, as well as practical device manufacturing and device testing. Here the emphasis is on novel flexible polyester-foil-based devices. The final part deals with applications with emphasis on architectural “smart” windows capable of achieving improved indoor comfort jointly with significant energy savings due to lowered demands for space cooling. Eyewear applications are touched upon as well.

1,156 citations


Journal ArticleDOI
Oluseun Adewumi1, Behrouz Aflatoonian2, Lars Ährlund-Richter3, Michal Amit4, Peter W. Andrews2, Gemma Beighton5, Paul Bello6, Nissim Benvenisty7, Lorraine S. Berry1, Simon Bevan, Barak Blum7, Justin Brooking8, Kevin G. Chen9, Andre Bh Choo, Gary A. Churchill, Marie Corbel10, Ivan Damjanov11, John S Draper12, Petr Dvorak13, Petr Dvorak14, Katarina Emanuelsson, Roland A. Fleck1, Angela Ford2, Karin Astrid Maria Gertow6, Karin Astrid Maria Gertow3, Marina Gertsenstein12, Paul J. Gokhale2, Rebecca S. Hamilton9, Alex Hampl13, Alex Hampl14, Lyn Healy1, Outi Hovatta3, Johan Hyllner, Marta P. Imreh3, Marta P. Imreh15, Joseph Itskovitz-Eldor4, Jamie P. Jackson2, Jackie Johnson6, Mark Jones2, Kehkooi Kee16, Benjamin L. King, Barbara B. Knowles, Majlinda Lako17, Franck Lebrin18, Barbara S. Mallon9, Daisy Manning19, Yoav Mayshar7, Ronald D.G. McKay9, Anna E. Michalska6, Milla Mikkola20, Masha Mileikovsky12, Stephen L. Minger21, Harry Moore2, Christine L. Mummery, Andras Nagy, Norio Nakatsuji22, Carmel M. O’Brien6, Steve Oh, Cia Olsson20, Timo Otonkoski20, Kye-Yoon Park9, Robert Passier, Hema Patel1, Minal Patel21, Roger A. Pedersen10, Martin F. Pera23, Marian S Piekarczyk19, Renee A. Reijo Pera16, Benjamin Reubinoff, Allan J. Robins, Janet Rossant12, Peter J. Rugg-Gunn12, Peter J. Rugg-Gunn10, Thomas C Schulz, Henrik Semb, Eric S Sherrer, Henrike Siemen16, Glyn Stacey1, Miodrag Stojkovic17, Hirofumi Suemori22, Jin P. Szatkiewicz, Tikva Turetsky, Timo Tuuri20, Steineke van den Brink, Kristina Vintersten12, Sanna Vuoristo20, Dorien Ward, Thomas A Weaver, Lesley Young1, Weidong Zhang 
TL;DR: The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide and found that despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers ofhuman embryonic stem cells.
Abstract: The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.

1,064 citations


Journal ArticleDOI
TL;DR: This protocol describes the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model, and can be used to trace the permeability of a test compound in two directions.
Abstract: Permeability coefficients across monolayers of the human colon carcinoma cell line Caco-2, cultured on permeable supports, are commonly used to predict the absorption of orally administered drugs and other xenobiotics. This protocol describes our method for the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model. A few modifications that have been introduced over the years are incorporated in the protocol. The method can be used to trace the permeability of a test compound in two directions, from the apical to the basolateral side or vice versa, and both passive and active transport processes can be studied. The permeability assay can be completed within one working day, provided that the Caco-2 monolayers have been cultured and differentiated on the permeable supports 3 weeks in advance.


Journal ArticleDOI
TL;DR: The present document serves as a stand‐alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function.
Abstract: Purpose: We updated the terminology in the field of pediatric lower urinary tract function. Materials and Methods: Discussions were held in the board of the International Children's Continence Society and an extensive reviewing process was done involving all members of the International Children's Continence Society, the urology section of the American Academy of Pediatrics, the European Society of Pediatric Urology, as well as other experts in the field. Results and Conclusions: New definitions and a standardized terminology are provided, taking into account changes in the adult sphere and new research results.

Journal ArticleDOI
TL;DR: The characteristics and expression of sex-biased genes, and the selective forces that shape this previously unappreciated source of phenotypic diversity, are discussed.
Abstract: Differences between males and females in the optimal phenotype that is favoured by selection can be resolved by the evolution of differential gene expression in the two sexes. Microarray experiments have shown that such sex-biased gene expression is widespread across organisms and genomes. Sex-biased genes show unusually rapid sequence evolution, are often labile in their pattern of expression, and are non-randomly distributed in the genome. Here we discuss the characteristics and expression of sex-biased genes, and the selective forces that shape this previously unappreciated source of phenotypic diversity. Sex-biased gene expression has implications beyond just evolutionary biology, including for medical genetics.

Journal ArticleDOI
TL;DR: GenX is a versatile program using the differential evolution algorithm for fitting X-ray and neutron reflectivity data, utilizes the Parratt recursion formula for simulating specular reflectivity, and can fit an arbitrary number of data sets simultaneously.
Abstract: GenX is a versatile program using the differential evolution algorithm for fitting X-ray and neutron reflectivity data. It utilizes the Parratt recursion formula for simulating specular reflectivity. The program is easily extensible, allowing users to incorporate their own models into the program. This can be useful for fitting data from other scattering experiments, or for any other minimization problem which has a large number of input parameters and/or contains many local minima, where the differential evolution algorithm is suitable. In addition, GenX manages to fit an arbitrary number of data sets simultaneously. The program is released under the GNU General Public License.

Journal ArticleDOI
TL;DR: In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night.

Journal ArticleDOI
TL;DR: A review of recent advances in the use of Sn or Si-based electrodes together with the remaining challenges to be addressed and issues to be solved prior to such electrodes being commercially implemented in Li-ion cells is presented in this paper.
Abstract: In the race for better Li-ion batteries, research on anode materials is very intensive as there is a strong desire to find alternatives to carbonaceous negative electrodes. A large part of these studies is devoted to alloying reactions, which have been known for more than thirty years but that have regained great interest by downsizing particle sizes, moving to nano-textured/nanostructured composites, or designing new electrode concepts. It is not the scope of this review to retrace twenty-five years of research, but rather to highlight recent advances that have been made in the use of Sn or Si-based electrodes together with the remaining challenges to be addressed and issues to be solved prior to such electrodes being commercially implemented in Li-ion cells.

Journal ArticleDOI
TL;DR: In this article, a perspective on an underlying practical challenge: designing communities that balance settlement density with satisfactory access to nature experience is presented. But, the authors do not consider how people actually achieve restoration in urban and natural environments.
Abstract: Urbanicity presents a challenge for the pursuit of sustainability. High settlement density may offer some environmental, economic, and social advantages, but it can impose psychological demands that people find excessive. These demands of urban life have stimulated a desire for contact with nature through suburban residence, leading to planning and transportation practices that have profound implications for the pursuit of sustainability. Some might dismiss people's desire for contact with nature as the result of an anti-urban bias in conjunction with a romantic view of nature. However, research in environmental psychology suggests that people's desire for contact with nature serves an important adaptive function, namely, psychological restoration. Based on this insight, we offer a perspective on an underlying practical challenge: designing communities that balance settlement density with satisfactory access to nature experience. We discuss research on four issues: how people tend to believe that nature is restorative; how restoration needs and beliefs shape environmental preferences; how well people actually achieve restoration in urban and natural environments; and how contact with nature can promote health. In closing, we consider urban nature as a design option that promotes urban sustainability.

Journal ArticleDOI
07 Sep 2007-Science
TL;DR: Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association with glaucoma, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS).
Abstract: Glaucoma is a leading cause of irreversible blindness A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q241 region associated with glaucoma Further investigation revealed that the association is confined to exfoliation glaucoma (XFG) Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS) About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes The population-attributable risk is more than 99% The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG

Journal ArticleDOI
TL;DR: This article summarizes the present knowledge and gives an insight into the future procedures to handle the nonequilibrium radiation dosimetry problems and is anticipated that new miniature detectors with controlled perturbations and corrections will be available to meet the demand for accurate measurements.
Abstract: Advances in radiation treatment with beamlet-based intensity modulation, image-guided radiation therapy, and stereotactic radiosurgery (including specialized equipments like CyberKnife, Gamma Knife, tomotherapy, and high-resolution multileaf collimating systems) have resulted in the use of reduced treatment fields to a subcentimeter scale. Compared to the traditional radiotherapy with fields > or =4 x 4 cm2, this can result in significant uncertainty in the accuracy of clinical dosimetry. The dosimetry of small fields is challenging due to nonequilibrium conditions created as a consequence of the secondary electron track lengths and the source size projected through the collimating system that are comparable to the treatment field size. It is further complicated by the prolonged electron tracks in the presence of low-density inhomogeneities. Also, radiation detectors introduced into such fields usually perturb the level of disequilibrium. Hence, the dosimetric accuracy previously achieved for standard radiotherapy applications is at risk for both absolute and relative dose determination. This article summarizes the present knowledge and gives an insight into the future procedures to handle the nonequilibrium radiation dosimetry problems. It is anticipated that new miniature detectors with controlled perturbations and corrections will be available to meet the demand for accurate measurements. It is also expected that the Monte Carlo techniques will increasingly be used in assessing the accuracy, verification, and calculation of dose, and will aid perturbation calculations of detectors used in small and highly conformal radiation beams. rican Association of Physicists in Medicine.

Journal ArticleDOI
TL;DR: The development of a genotyping array with ∼27,000 SNPs is reported and it is shown that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only ∼20 dogs, showing that trait mapping within dog breeds will be highly efficient and generally applicable to trait mapping.
Abstract: With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with approximately 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only approximately 20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting (S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of approximately 100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health.

Journal ArticleDOI
TL;DR: In this paper, the authors identify a set of issues that have slipped through the net of some of the existing IB frameworks and propose a framework that is found at the intersection of entrepreneurial and internationalisation perspectives, which is known as international entrepreneurial dynamics.
Abstract: The initial stages of internationalisation, prior to firms having established their definitive sources of advantage, remain the relatively unexplored area of the international business (IB) literature. At these early stages, where firms are seeking to establish themselves, and new multinational firms are appearing to exploit new opportunities created by globalisation, the entrepreneurial aspects of internationalisation come to the fore. In this paper we aim to delineate an emerging field of IB scholarship: we use the appearance of international new ventures, and the phenomenon of accelerated internationalisation that they feature, to identify a set of issues that has slipped through the net of some of the existing IB frameworks. We propose that the salient features of accelerated and early internationalisation by the newly internationalising firm are best captured in a framework that is found at the intersection of entrepreneurial and internationalisation perspectives, which we propose be known as international entrepreneurial dynamics. We discuss such a framework in terms of entry points and pathways mapped by firms as they probe the IB arena, and the key factors that impinge on behaviour and strategic choices. In line with recent developments in the entrepreneurship literature, these are grouped into three milestones of entrepreneurial processes that extend across national boundaries: (1) the discovery of new opportunities; (2) the deployment of resources in the exploitation of these opportunities; and (3) the engagement with competitors. Implications for MNE and internationalisation theory are discussed.

Journal ArticleDOI
TL;DR: A meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic coLECTomy for cancer is oncologically safe was performed.
Abstract: OBJECTIVE: To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colect ...

Journal ArticleDOI
TL;DR: Birkinshaw and Hood as mentioned in this paper investigated the strategic roles of subsidiaries in MNCs, and raised the issue of how difficult it is for headquarters to remain in control of its subsidiaries and to influence their strategies over time.
Abstract: The contest for intra-organisational power in the multinational corporation (MNC) has gradually become a prominent issue on the research agenda. As long as 25 years ago, Hedlund (1980) investigated the strategic roles of subsidiaries in MNCs, and Doz and Prahalad (1981) raised the issue of how difficult it is for headquarters to remain in control of its subsidiaries and to influence their strategies over time. Since then, several researchers have suggested that MNCs can be considered to be dispersed structures of power in which the top management’s authority does not necessarily result in hierarchical power being the ultimate control mechanism (Hedlund, 1986; Forsgren, 1989; Ghoshal and Bartlett, 1990; Doz and Prahalad, 1993; Ferner and Edwards, 1995; Kristensen and Zeitlin, 2001; Morgan and Whitley, 2003). Birkinshaw and Hood (1998) examined the evolution of capabilities at the subsidiary level and recognised that, in most corporations, there is an ‘internal competition for charter’ that implies a process of change in subsidiary roles (Birkinshaw and Hood, 1998: 782). Case research has also indicated that changes in the charters of divisions or subsidiaries in MNCs constitute a strong feature of horizontal or vertical competition in the corporate ‘marketplace’ (Galunic and Eisenhardt, 1996; Birkinshaw and Fry, 1998). The tension between the headquarters and overseas laboratories caused by the laboratories’ desire for autonomy and influence is an example of such a competition (Asaka wa, 2001).

Journal ArticleDOI
TL;DR: In this article, the authors present new data on the direct and deliberate killings of civilians, called one-sided violence, in intrastate armed conflicts, 1989-2004, and show that the post-Cold War era is characterized by periods of fairly low-scale violence punctuated by occasional sharp increases in violence against civilians.
Abstract: This article presents new data on the direct and deliberate killings of civilians, called one-sided violence, in intrastate armed conflicts, 1989—2004. These data contribute to the present state of quantitative research on violence against civilians in three important respects: the data provide actual estimates of civilians killed, the data are collected annually and the data are provided for both governments and rebel groups. Using these data, general trends and patterns are presented, showing that the post-Cold War era is characterized by periods of fairly low-scale violence punctuated by occasional sharp increases in violence against civilians. Furthermore, rebels tend to be more violent on the whole, while governments commit relatively little violence except in those few years which see mass killings. The article then examines some factors that have been found to predict genocide and evaluates how they correlate with one-sided violence as conceptualized here. A U-shaped correlation between regime type and one-sided violence is identified: while autocratic governments undertake higher levels of one-sided violence than other regime types, rebels are more violent in democratic countries.

Journal ArticleDOI
TL;DR: The evidence for pheromones as indicators of mate quality is reviewed and the extent of their use in individual mate assessment is examined, highlighting potential areas for future research and the need for interdisciplinary research that combines exploration of chemical, physiological and behavioural processes to further understand the role of chemical cues in mate assessment.
Abstract: Chemical signals are omnipresent in sexual communication in the vast majority of living organisms. The traditional paradigm was that their main purpose in sexual behaviour was to coordinate mate and species recognition and thus pheromones were conserved in structure and function. In recent years, this view has been challenged by theoretical analyses on the evolution of pheromones and empirical reports of mate choice based on chemical signals. The ability to measure precisely the quantity and quality of chemicals emitted by single individuals has also revealed considerable individual variation in chemical composition and release rates, and there is mounting evidence that prospecting mates respond to this variation. Here, we review the evidence for pheromones as indicators of mate quality and examine the extent of their use in individual mate assessment. We begin by briefly defining the levels of mate choice--species recognition, mate recognition and mate assessment. We then explore the degree to which pheromones satisfy the key criteria necessary for their evolution and maintenance as cues in mate assessment; that is, they should exhibit variation across individuals within a sex and species; they should honestly reflect an individual's quality and thus be costly to produce and/or maintain; they should display relatively high levels of heritability. There is now substantial empirical evidence that pheromones can satisfy all these criteria and, while measurements of the actual metabolic cost of pheromone production remain to some degree lacking, trade-offs between pheromone production and various fitness-related characters such as growth rate, immunocompetence and longevity have been reported for a range of species. In the penultimate section, we outline the growing number of studies where the consequences of chemical-based mate assessment have been investigated, specifically focussing on the reported direct and genetic benefits accrued by the receiver. Finally, we highlight potential areas for future research and in particular emphasise the need for interdisciplinary research that combines exploration of chemical, physiological and behavioural processes to further our understanding of the role of chemical cues in mate assessment.

Journal ArticleDOI
TL;DR: Conclusions from clinical trial results that are derived from model‐based analyses rely on the model adequately describing the underlying system and without an understanding of the properties of thesediagnostics, development and use of new diagnostics, and additional information pertaining to the diagnosis, there is risk that adequate models will be rejected and inadequate models accepted.
Abstract: Conclusions from clinical trial results that are derived from model-based analyses rely on the model adequately describing the underlying system. The traditionally used diagnostics intended to provide information about model adequacy have seldom discussed shortcomings. Without an understanding of the properties of these diagnostics, development and use of new diagnostics, and additional information pertaining to the diagnostics, there is risk that adequate models will be rejected and inadequate models accepted. Thus, a diagnosis of available diagnostics is desirable.

Journal ArticleDOI
TL;DR: The methodology is sufficiently robust to measure and compare pressure ulcer prevalence in different countries and indicates that more attention to prevention is needed in Europe.
Abstract: Rationale and aims Numerous prevalence studies have been conducted. The problem with these studies is that prevalence proportions cannot be compared with each other, because of differences in performance of each survey. There is no agreed standardized method for determining prevalence proportions. This study aimed to develop and pilot a uniform data collection instrument and methodology to measure the pressure ulcer prevalence and to get some insight into pressure ulcer prevalence across different patient groups in Europe. Methods Pressure ulcer experts from different European countries developed a data collection instrument, which included five categories of data: general data, patient data, risk assessment, skin observation and prevention. A convenience sample of university and general hospitals of Belgium, Italy, Portugal, UK and Sweden participated in the study. In each participating hospital, teams of two trained nurses who collected the data on the wards were established. All patients admitted before midnight on the day of the survey and older than 18 years were included. Results The data collection instrument and study procedure of the survey were found to be effective by all participants. 5947 patients were surveyed in 25 hospitals in five European countries. The pressure ulcer prevalence (grade 1–4) was 18.1% and if grade 1 ulcers were excluded, it was 10.5%. The sacrum and heels were the most affected locations. Only 9.7% of the patients in need of prevention received fully adequate preventive care. Conclusion The methodology is sufficiently robust to measure and compare pressure ulcer prevalence in different countries. The pressure ulcer prevalence was higher than expected and relatively few patients received adequate prevention. This indicates that more attention to prevention is needed in Europe.

Journal ArticleDOI
TL;DR: This paper investigated the linkage between drivers, mechanisms and barriers to knowledge creation and acquisition at the micro-level, and the development over time and across spatial settings of higher-order phenomena of localized institutions and other capabilities.
Abstract: This article aims to show how processes of knowledge development and their institutional underpinnings make up the core of evolutionary economic geography. We argue that micro level concepts—notably innovation, selection and retention—provide insights that can be helpful also when investigating evolutionary processes of knowledge creation at the aggregate levels of cities, regions or nations. We investigate the linkage between drivers, mechanisms and barriers to knowledge creation and acquisition at the micro-level, and the development over time and across spatial settings of higher-order phenomena of localized institutions and other capabilities. We apply this distinction on the analysis of the rise, growth, decline and possible rejuvenation of spatial clusters of similar and complementary economic activity.

Journal ArticleDOI
TL;DR: A new pattern of interactions is described between the two major known genetic risk factors and the major environmental risk factor concerning the risk of developing anti-CCP-positive RA, extending the basis for a pathogenetic hypothesis for RA involving genetic and environmental factors.
Abstract: Gene-gene and gene-environment interactions are key features in the development of rheumatoid arthritis (RA) and other complex diseases. The aim of this study was to use and compare three different definitions of interaction between the two major genetic risk factors of RA—the HLA-DRB1 shared epitope (SE) alleles and the PTPN22 R620W allele—in three large case-control studies: the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, the North American RA Consortium (NARAC) study, and the Dutch Leiden Early Arthritis Clinic study (in total, 1,977 cases and 2,405 controls). The EIRA study was also used to analyze interactions between smoking and the two genes. “Interaction” was defined either as a departure from additivity, as interaction in a multiplicative model, or in terms of linkage disequilibrium—for example, deviation from independence of penetrance of two unlinked loci. Consistent interaction, defined as departure from additivity, between HLA-DRB1 SE alleles and the A allele of PTPN22 R620W was seen in all three studies regarding anti-CCP–positive RA. Testing for multiplicative interactions demonstrated an interaction between the two genes only when the three studies were pooled. The linkage disequilibrium approach indicated a gene-gene interaction in EIRA and NARAC, as well as in the pooled analysis. No interaction was seen between smoking and PTPN22 R620W. A new pattern of interactions is described between the two major known genetic risk factors and the major environmental risk factor concerning the risk of developing anti-CCP–positive RA. The data extend the basis for a pathogenetic hypothesis for RA involving genetic and environmental factors. The study also raises and illustrates principal questions concerning ways to define interactions in complex diseases.