Showing papers by "University of Glasgow published in 2005"
TL;DR: This review discusses the synthetic chemistry, fluid stabilization and surface modification of superparamagnetic iron oxide nanoparticles, as well as their use for above biomedical applications.
6,207 citations
Book•
16 Dec 2005TL;DR: Systematic review methods have been widely used in health care, and are becoming increasingly common in the social sciences (fostered by the work of the Campbell Collaboration) as mentioned in this paper.
Abstract: Such diverse thinkers as Lao-Tze, Confucius, and U.S. Defense Secretary Donald Rumsfeld have all pointed out that we need to be able to tell the difference between real and assumed knowledge. The systematic review is a scientific tool that can help with this difficult task. It can help, for example, with appraising, summarising, and communicating the results and implications of otherwise unmanageable quantities of data. This is important because quite often there are so many studies, and their results are often so conflicting, that no policymaker or practitioner could possibly carry out this task themselves.Systematic review methods have been widely used in health care, and are becoming increasingly common in the social sciences (fostered, for example, by the work of the Campbell Collaboration).
This book outlines the rationale and methods of systematic reviews, giving worked examples from social science and other fields. It requires no previous knowledge, but takes the reader through the process stage by stage. It draws on examples from such diverse fields as psychology, criminology, education, transport, social welfare, public health, and housing and urban policy, among others.The book includes detailed sections on assessing the quality of both quantitative, and qualitative research; searching for evidence in the social sciences;meta-analytic and other methods of evidence synthesis; publication bias; heterogeneity; and approaches to dissemination.
3,263 citations
TL;DR: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of least-in- LDL cholesterol levels per day, with a greater incidence of elevated aminotransferase levels.
Abstract: background Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). methods A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. results The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. conclusions Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.
3,141 citations
TL;DR: The basis of the CD approach and its application to the study of proteins, and clear guidelines on how reliable data can be obtained and analysed are presented.
3,023 citations
TL;DR: The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol- based regimen, and these effects might not be entirely explained by better control of blood pressure.
2,595 citations
TL;DR: It is seen that many PID variants have been developed in order to improve transient performance, but standardising and modularising PID control are desired, although challenging, and the inclusion of system identification and "intelligent" techniques in software based PID systems helps automate the entire design and tuning process to a useful degree.
Abstract: Designing and tuning a proportional-integral-derivative (PID) controller appears to be conceptually intuitive, but can be hard in practice, if multiple (and often conflicting) objectives such as short transient and high stability are to be achieved. Usually, initial designs obtained by all means need to be adjusted repeatedly through computer simulations until the closed-loop system performs or compromises as desired. This stimulates the development of "intelligent" tools that can assist engineers to achieve the best overall PID control for the entire operating envelope. This development has further led to the incorporation of some advanced tuning algorithms into PID hardware modules. Corresponding to these developments, this paper presents a modern overview of functionalities and tuning methods in patents, software packages and commercial hardware modules. It is seen that many PID variants have been developed in order to improve transient performance, but standardising and modularising PID control are desired, although challenging. The inclusion of system identification and "intelligent" techniques in software based PID systems helps automate the entire design and tuning process to a useful degree. This should also assist future development of "plug-and-play" PID controllers that are widely applicable and can be set up easily and operate optimally for enhanced productivity, improved quality and reduced maintenance requirements.
2,461 citations
TL;DR: The physiological origin of MDA is described, its toxicity is highlighted, and the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions.
Abstract: Summary Aim Of the many biological targets of oxidative stress, lipids are the most involved class of biomolecules. Lipid oxidation gives rise to a number of secondary products. Malondialdehyde (MDA) is the principal and most studied product of polyunsaturated fatty acid peroxidation. This aldehyde is a highly toxic molecule and should be considered as more than just a marker of lipid peroxidation. Its interaction with DNA and proteins has often been referred to as potentially mutagenic and atherogenic. This review is intended to briefly describe the physiological origin of MDA, to highlight its toxicity, describe and comment on the most recent methods of detection and discuss its occurrence and significance in pathology. Data synthesis In vivo origin as well as reactivity and consequent toxicity of MDA are reviewed. The most recent and improved procedures for the evaluation of MDA in biological fluids are described and discussed. The evidence of the occurrence of increased MDA levels in pathology is described. Conclusions In the assessment of MDA, the most common methods of detection are insufficiently sensitive and disturbed by interference coming from related species or overestimation derived from stressing analysis conditions. Moreover, no recent nutritional or medical trials report the use of one of the new and more reliable methods, some of which are undoubtedly accessible to virtually all the laboratories provided with a common HPLC or a spectrofluorimeter.
2,077 citations
TL;DR: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure, providing further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.
Abstract: background Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. methods We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. results
1,997 citations
TL;DR: In this article, the authors trace the links between neoliberalism and globalization on the one hand, and the knowledge economy on the other, and argue that the role of higher education for the economy is seen by governments as having greater importance to the extent that higher education has become the new star ship in the policy fleet for governments.
Abstract: The ascendancy of neoliberalism and the associated discourses of ‘new public management’, during the 1980s and 1990s has produced a fundamental shift in the way universities and other institutions of higher education have defined and justified their institutional existence. The traditional professional culture of open intellectual enquiry and debate has been replaced with a institutional stress on performativity, as evidenced by the emergence of an emphasis on measured outputs: on strategic planning, performance indicators, quality assurance measures and academic audits. This paper traces the links between neoliberalism and globalization on the one hand, and neoliberalism and the knowledge economy on the other. It maintains that in a global neoliberal environment, the role of higher education for the economy is seen by governments as having greater importance to the extent that higher education has become the new star ship in the policy fleet for governments around the world. Universities are seen as a key driver in the knowledge economy and as a consequence higher education institutions have been encouraged to develop links with industry and business in a series of new venture partnerships. The recognition of economic importance of higher education and the necessity for economic viability has seen initiatives to promote greater entrepreneurial skills as well as the development of new performative measures to enhance output and to establish and achieve targets. This paper attempts to document these trends at the level of both political philosophy and economic theory.
1,914 citations
TL;DR: Eight factors in early life are associated with an increased risk of obesity in childhood, including parental obesity and catch-up growth.
Abstract: Objective To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom.
Design Prospective cohort study.
Setting Avon longitudinal study of parents and children, United Kingdom.
Participants 8234 children in cohort aged 7 years and a subsample of 909 children (children in focus) with data on additional early growth related risk factors for obesity.
Main outcome measures Obesity at age 7 years, defined as a body mass index 3 95th centile relative to reference data for the UK population in 1990.
Results Eight of 25 putative risk factors were associated with a risk of obesity in the final models: parental obesity (both parents: adjusted odds ratio, 10.44, 95% confidence interval 5.11 to 21.32), very early (by 43 months) body mass index or adiposity rebound (15.00, 5.32 to 42.30), more than eight hours spent watching television per week at age 3 years (1.55, 1.13 to 2.12), catch-up growth (2.60, 1.09 to 6.16), standard deviation score for weight at age 8 months (3.13, 1.43 to 6.85) and 18 months (2.65, 1.25 to 5.59); weight gain in first year (1.06, 1.02 to 1.10 per 100 g increase); birth weight, per 100 g (1.05, 1.03 to 1.07); and short (< 10.5 hours) sleep duration at age 3 years (1.45, 1.10 to 1.89).
Conclusion Eight factors in early life are associated with an increased risk of obesity in childhood.
1,690 citations
Wellcome Trust Sanger Institute1, George Washington University2, J. Craig Venter Institute3, University of Glasgow4, University of Oxford5, Newcastle University6, University of Bordeaux7, University of Cambridge8, Oregon Health & Science University9, University of Dundee10, Imperial College London11, Case Western Reserve University12, Yale University13, Université catholique de Louvain14, University of Iowa15, Wellcome Trust16
TL;DR: Comparisons of the cytoskeleton and endocytic trafficking systems of Trypanosoma brucei with those of humans and other eukaryotic organisms reveal major differences.
Abstract: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including ∼900 pseudogenes and ∼1700 T. brucei–specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
TL;DR: The various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance are discussed.
Abstract: Toll-like receptors (TLRs) are involved in host defence against invading pathogens, functioning as primary sensors of microbial products and activating signalling pathways that induce the expression of immune and pro-inflammatory genes. However, TLRs have also been implicated in several immune-mediated and inflammatory diseases. As the immune system needs to constantly strike a balance between activation and inhibition to avoid detrimental and inappropriate inflammatory responses, TLR signalling must be tightly regulated. Here, we discuss the various negative regulatory mechanisms that have evolved to attenuate TLR signalling to maintain this immunological balance.
Wellcome Trust Sanger Institute1, Seattle Biomed2, Katholieke Universiteit Leuven3, GATC Biotech4, Max Planck Society5, Washington University in St. Louis6, University of Trieste7, International Centre for Genetic Engineering and Biotechnology8, European Bioinformatics Institute9, University of São Paulo10, National Scientific and Technical Research Council11, Université catholique de Louvain12, University of London13, University of Edinburgh14, University of Glasgow15, University of Wisconsin-Madison16, University of York17, University of Cambridge18, University of Washington19
TL;DR: The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Tritryp genomes suggest that the mechanisms regulating RNA polymerase II–directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling.
Abstract: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.
George Washington University1, Seattle Biomed2, University of Washington3, J. Craig Venter Institute4, Karolinska Institutet5, University of California, Los Angeles6, Universidade Federal de Minas Gerais7, Uppsala University8, Centre national de la recherche scientifique9, University of Glasgow10, University of Cambridge11, Federal University of São Paulo12, Children's Hospital Oakland Research Institute13, Johns Hopkins University School of Medicine14, National Research Council15, University of Oxford16, University of London17, University of Massachusetts Amherst18, Oswaldo Cruz Foundation19, University of Buenos Aires20, Central University of Venezuela21, National University of Singapore22, University of Georgia23
TL;DR: Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Abstract: Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
Broad Institute1, J. Craig Venter Institute2, Stanford University3, Oregon Health & Science University4, University of Glasgow5, Genetic Information Research Institute6, Institut Universitaire de France7, University of Kentucky8, University of Nebraska–Lincoln9, University of Göttingen10, Pasteur Institute11, University of São Paulo12, Texas A&M University13, Wellcome Trust Sanger Institute14, John Innes Centre15, University of Wisconsin-Madison16, Max Planck Society17, University of Oregon18, University of Nottingham19, Spanish National Research Council20, Ohio State University21, University of Georgia22, Tokyo Institute of Technology23, National Institute of Advanced Industrial Science and Technology24, George Washington University25, University of Manchester26, University of Liverpool27, University of Melbourne28, Karlsruhe Institute of Technology29, University of Idaho30
TL;DR: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution, and a comparative study with Aspergillus fumigatus and As pergillus oryzae, used in the production of sake, miso and soy sauce, provides new insight into eukaryotic genome evolution and gene regulation.
Abstract: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.
TL;DR: It is shown that SM, a patient with rare bilateral amygdala damage, shows an inability to make normal use of information from the eye region of faces when judging emotions, a defect the authors trace to a lack of spontaneous fixations on the eyes during free viewing of faces.
Abstract: Ten years ago, we reported that SM, a patient with rare bilateral amygdala damage, showed an intriguing impairment in her ability to recognize fear from facial expressions. Since then, the importance of the amygdala in processing information about facial emotions has been borne out by a number of lesion and functional imaging studies. Yet the mechanism by which amygdala damage compromises fear recognition has not been identified. Returning to patient SM, we now show that her impairment stems from an inability to make normal use of information from the eye region of faces when judging emotions, a defect we trace to a lack of spontaneous fixations on the eyes during free viewing of faces. Although SM fails to look normally at the eye region in all facial expressions, her selective impairment in recognizing fear is explained by the fact that the eyes are the most important feature for identifying this emotion. Notably, SM's recognition of fearful faces became entirely normal when she was instructed explicitly to look at the eyes. This finding provides a mechanism to explain the amygdala's role in fear recognition, and points to new approaches for the possible rehabilitation of patients with defective emotion perception.
TL;DR: In this article, a large-scale individual participant meta-analysis was conducted to assess the relationship of fibrinogen levels with risk of major vascular and non-vascular outcomes based on individual participant data.
Abstract: CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
TL;DR: Computational modelling indicates that scaffolding proteins and endogenous inhibitors can determine the dynamic biological behaviour of the pathway from Ras through Raf and MEK to ERK/MAPK.
Abstract: The pathway from Ras through Raf and MEK (MAPK and ERK kinase) to ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase) regulates many fundamental cellular processes. Recently, a number of scaffolding proteins and endogenous inhibitors have been identified, and their important roles in regulating signalling through this pathway are now emerging. Some scaffolds augment the signal flux, but also mediate crosstalk with other pathways; certain adaptors target MEK-ERK/MAPK complexes to subcellular localizations; others provide regulated inhibition. Computational modelling indicates that, together, these modulators can determine the dynamic biological behaviour of the pathway.
TL;DR: Arnab et al. as mentioned in this paper describe non-representational theory as an umbrella term for diverse work that seeks better to cope with our self-evidently more-than-human, morethan-textual, multisensual worlds.
Abstract: © 2005 Edward Arnold (Publishers) Ltd 10.1191/0309132505ph531pr I Parameters, definitions and themes This is the first of three reports I will write covering an emergent area of research in cultural geography and its cognate fields. During recent years, ‘non-representational theory’ has become as an umbrella term for diverse work that seeks better to cope with our self-evidently more-than-human, more-than-textual, multisensual worlds. In as much as nonrepresentational work allows it, these reports will sketch out common themes of interest, and assess impacts, critics and potentials, variously conceptual, methodological and empirical. Of late, non-representational theorists have asked difficult and provocative questions of cultural geographers, and many others in the discipline, about what is intended by the conduct of research (Thrift and Dewsbury, 2000). What has been identified as deadening effect – the tendency for cultural analyses to cleave towards a conservative, categorical politics of identity and textual meaning – can, it is contended, be overcome by allowing in much more of the excessive and transient aspects of living. Given the scope and force of the original non-representational arguments, it is unsurprising that this theory has been subject to fulsome response. In fact, non-representational theory has become a particularly effective lightning-rod for disciplinary self-critique. Commentaries have emerged from within cultural, feminist and Marxian traditions and the more recent coalition of critical geography. Notably, and anecdotally, some of the most colourful observations have been saved for bi-partisan conversation in the conference or common room. It is important (not to say appropriate) that the nature of the dialogue – variously confrontational, tribal, dogmatic, peevish and full-bodied – goes on record early. Published versions have been concerned predominantly with the theoretical conditions for disciplinary succession or progression that the term ‘non-representational’ would seem to imply and how, in relation, the concept of performance should be understood by geographers. These articles are variously structured as manifesto, critical review, restated challenge, revanchist programme and proposed reconciliation (Thrift, 1996; 1997; 2000; Nelson, 1999; Thrift and Dewsbury, 2000; Nash, 2000; Harrison, 2000; Gregson and Rose, 2000; Crouch, 2001; Dewsbury et al., 2002; Whatmore, 2002; Cresswell, 2002; Smith, 2003; Jacobs and Nash, 2003; Latham, 2003a; Castree and MacMillan, 2004).1 In this report, I would like to treat the flourishing theoretical debate as a significant Cultural geography: the busyness of being ‘more-than-representational’
TL;DR: This article presented a three-stage process of conceptual development in response to the call for a unifying direction for research in the emergent field of international entrepreneurship, drawing on classic approaches to internationalisation, and importing insight from entrepreneurship as a separate and distinct field of study.
Abstract: This paper presents a three-stage process of conceptual development in response to the call for a unifying direction for research in the emergent field of international entrepreneurship. Drawing on classic approaches to internationalisation, and importing insight from entrepreneurship as a separate and distinct field of study, the paper develops three potential models of internationalisation as a time-based process of entrepreneurial behaviour. The models evolve from the simple through general to precise levels of conceptualisation. Research implications are discussed.
TL;DR: A review of the role of dendrimers in those aspects of synthetic vector development is presented in this article, where the authors focus on the current understanding of the current role of Dendrimer-based transfection agents.
14 Dec 2005
TL;DR: Dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but therapeutic delivery of nucleic acids remains a challenge.
Abstract: Dendrimers have unique molecular architectures and properties that make them attractive materials for the development of nanomedicines. Key properties such as defined architecture and a high ratio of multivalent surface moieties to molecular volume also make these nanoscaled materials highly interesting for the development of synthetic (non-viral) vectors for therapeutic nucleic acids. Rational development of such vectors requires the link to be made between dendrimer structure and the morphology and physicochemistry of the respective nucleic acid complexes and, furthermore, to the biological performance of these systems at the cellular and systemic level. The review focuses on the current understanding of the role of dendrimers in those aspects of synthetic vector development. Dendrimer-based transfection agents have become routine tools for many molecular and cell biologists but therapeutic delivery of nucleic acids remains a challenge.
TL;DR: It is observed posttranscriptional gene silencing through translational repression of messenger RNA during sexual development, and a 47-base 3′ untranslated region motif is implicated in this process.
Abstract: Plasmodium berghei and Plasmodium chabaudi are widely used model malaria species. Comparison of their genomes, integrated with proteomic and microarray data, with the genomes of Plasmodium falciparum and Plasmodium yoelii revealed a conserved core of 4500 Plasmodium genes in the central regions of the 14 chromosomes and highlighted genes evolving rapidly because of stage-specific selective pressures. Four strategies for gene expression are apparent during the parasites' life cycle: (i) housekeeping; (ii) host-related; (iii) strategy-specific related to invasion, asexual replication, and sexual development; and (iv) stage-specific. We observed posttranscriptional gene silencing through translational repression of messenger RNA during sexual development, and a 47-base 3' untranslated region motif is implicated in this process.
TL;DR: Low-molecular-weight heparins is both safe and effective to prevent or treat venous thromboembolism in pregnancy.
TL;DR: It is shown that mitochondrial DNA variation in isolated “relict” populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia.
Abstract: A recent dispersal of modern humans out of Africa is now widely accepted, but the routes taken across Eurasia are still disputed. We show that mitochondrial DNA variation in isolated “relict” populations in southeast Asia supports the view that there was only a single dispersal from Africa, most likely via a southern coastal route, through India and onward into southeast Asia and Australasia. There was an early offshoot, leading ultimately to the settlement of the Near East and Europe, but the main dispersal from India to Australia ∼65,000 years ago was rapid, most likely taking only a few thousand years.
TL;DR: The disrupted in schizophrenia 1 (DISC1) gene is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness and a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP is proposed.
Abstract: The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3',5'-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting cells and releases it in an activated state in response to elevated cAMP.
TL;DR: The information underlying the recognition of the six basic facial expression signals is characterized and how efficiently each expression is decoded by the underlying brain structures is evaluated.
Abstract: This article examines the human face as a transmitter of expression signals and the brain as a decoder of these expression signals. If the face has evolved to optimize transmission of such signals, the basic facial expressions should have minimal overlap in their information. If the brain has evolved to optimize categorization of expressions, it should be efficient with the information available from the transmitter for the task. In this article, we characterize the information underlying the recognition of the six basic facial expression signals and evaluate how efficiently each expression is decoded by the underlying brain structures.
The Breast Cancer Research Foundation1, Netherlands Cancer Institute2, St James's University Hospital3, Carlos III Health Institute4, Autonomous University of Madrid5, German Cancer Research Center6, Leiden University7, University of Erlangen-Nuremberg8, Trinity College, Dublin9, University of Manchester10, Imperial College London11, University of Nantes12, Erasmus University Rotterdam13, University of Glasgow14, Max Delbrück Center for Molecular Medicine15, French Institute of Health and Medical Research16, University of Vienna17, University of London18, Cancer Research UK19
TL;DR: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCa1 mutation testing.
Abstract: Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
TL;DR: It is concluded that, although pathogen emergence is inherently unpredictable, emerging pathogens tend to share some common traits, and that directly transmitted RNA viruses might be the pathogens that are most likely to jump between host species.
Abstract: Novel pathogens continue to emerge in human, domestic animal, wildlife and plant populations, yet the population dynamics of this kind of biological invasion remain poorly understood. Here, we consider the epidemiological and evolutionary processes underlying the initial introduction and subsequent spread of a pathogen in a new host population, with special reference to pathogens that originate by jumping from one host species to another. We conclude that, although pathogen emergence is inherently unpredictable, emerging pathogens tend to share some common traits, and that directly transmitted RNA viruses might be the pathogens that are most likely to jump between host species.
TL;DR: It is demonstrated that human c-Myc also directly enhances Pol I transcription of ribosomal RNA (rRNA) genes, and proposed that stimulation of rRNA synthesis by c- myc is a key pathway driving cell growth and tumorigenesis.
Abstract: c-Myc coordinates cell growth and division through a transcriptional programme that involves both RNA polymerase (Pol) II- and Pol III-transcribed genes. Here, we demonstrate that human c-Myc also directly enhances Pol I transcription of ribosomal RNA (rRNA) genes. rRNA synthesis and accumulation occurs rapidly following activation of a conditional MYC-ER allele (coding for a Myc-oestrogen-receptor fusion protein), is resistant to inhibition of Pol II transcription and is markedly reduced by c-MYC RNA interference. Furthermore, by using combined immunofluorescence and rRNA-FISH, we have detected endogenous c-Myc in nucleoli at sites of active ribosomal DNA (rDNA) transcription. Our data also show that c-Myc binds to specific consensus elements located in human rDNA and associates with the Pol I-specific factor SL1. The presence of c-Myc at specific sites on rDNA coincides with the recruitment of SL1 to the rDNA promoter and with increased histone acetylation. We propose that stimulation of rRNA synthesis by c-Myc is a key pathway driving cell growth and tumorigenesis.