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- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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| 8. |
- Babar, Muhammad Ali, et al.
(författare)
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On the Importance of Sound Architectural Practices in the Use of OSS in Software Product Lines
- 2007
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Ingår i: Proceedings of the 2nd International Workshop on Open Source Software and Product Lines (OSSPL 2007), collocated with the 11th International Software Product Line Conference (SPLC 2007), Kyoto, Japan, September 10-14, 2007. - : Cosi. ; , s. 25-32
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Konferensbidrag (refereegranskat)abstract
- Software Product Line (SPL) and Open Source Software (OSS) haveemerged as successful modes of developing software. Although they appear todiffer in terms of development principles and processes, researchers andpractitioners have been increasingly emphasising the need to achieve synergiesby exploiting the ever growing repositories of OSS components for developingSPLs. While there have been calls for the SPL community to accelerate thewidespread use of OSS in SPL, less attention has been paid to how OSScommunities could increase the use of OSS components in SPL. Sincearchitectural issues are considered critical in the SPL community, we proposethat an increased attention on architectural aspects of OSS components mayprovide the confidence that organizations need in order for them to choose anduse OSS components in SPL. We identify a number of architectural practiceswhich are followed by the SPL community and discuss the possibilities for andpotential benefits of incorporating those practices in OSS developmentprocesses.
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| 9. |
- Corcoran, Paul A., et al.
(författare)
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The effect of different strains of Helicobacter pylori on platelet aggregation
- 2007
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Ingår i: Canadian Journal of Gastroenterology. - 0835-7900. ; 21:6, s. 367-370
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Helicobacter pylori is the major causative agent in peptic ulcer disease and is strongly implicated in the development of gastric cancer. It has also been linked, less strongly, to cardiovascular disease. The mechanisms by which certain Strains of H pylon induce platelet aggregation through interactions with platelet glycoprotein 1b have been previously described. METHODS: In the present study, 21 different strains of H pylori, varying in their vacuolating toxin gene, cytotoxic-associated gene A status and other pathogenicity factors, were tested for their ability to induce platelet agggregation. RESULTS: Ten of the 21 strains induced platelet aggregation, a response that appeared to be independent of their vacuolating toxin gene and cytotoxic-associated gene A status. CONCLUSIONS: Platelet aggregation has been suggested to be one of the possible mechanisms involved in the effects on the cardiovascular system induced by H pylori. Our results suggest that any putative role H pylon plays in cardiovascular disease may be strain dependent. Further work to identify the H pylon factors involved in induction of platelet aggregation may allow for identification of 'higher risk' strains for cardiovascular disease.
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- Eldridge, Bill, et al.
(författare)
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An in vitro selection strategy for conferring protease resistance to ligand binding peptides
- 2009
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 22:11, s. 691-698
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Tidskriftsartikel (refereegranskat)abstract
- One drawback to the use of peptides as therapeutics has been their susceptibility to proteolysis. Here, we have used an in vitro display technology, CIS display, to enhance the proteolytic resistance of ligand-binding peptides by selection of protecting motifs from a large peptide library. The premise to this selection was that certain linear peptides within a library could form structures capable of preventing the access of proteases to defined cleavage sites without affecting ligand binding. A diverse 12-mer peptide library was inserted between a FLAG epitope motif and a thrombin cleavage site and this construct was fused to the bacterial initiator protein RepA for CIS display selection. After five rounds of selection, protection motifs were isolated that were capable of preventing proteolytic cleavage of the adjacent thrombin site. Some of the selected peptides were also resistant to more promiscuous proteases, such as chymotrypsin and trypsin, which were not used in the selection. The observed resistance to thrombin, trypsin and chymotrypsin translated into increased resistance to plasma proteases in vitro and to an increase in circulating half-lives in rats. This method can be applied to enhancing the in vivo stability of therapeutic peptides.
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- Graham, Ian, et al.
(författare)
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European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
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Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
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Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
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| 14. |
- Lagerstedt, Jens O., 1975, et al.
(författare)
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Mapping the structural transition in an amyloidogenic apolipoprotein A-I
- 2007
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Ingår i: Biochemistry. - 0006-2960. ; 46:34, s. 9693-9
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Tidskriftsartikel (refereegranskat)abstract
- The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIOWA) leads to the formation of beta-secondary structure rich amyloid fibrils in vivo. Here we show that full-length apoA-IIOWA has a decreased lipid-binding capability, an increased amino-terminal sensitivity to protease, and a propensity to form annular protofibrils visible by electron microscopy. The molecular basis for the conversion of apolipoprotein A-I to a proamyloidogenic form was examined by electron paramagnetic resonance spectroscopy. Our recent findings [Lagerstedt, J. O., Budamagunta, M. S., Oda, M. N., and Voss, J. C. (2007) J. Biol. Chem. 282, 9143-9149] indicate that Gly26 in the native apoprotein separates a preceding beta-strand structure (residues 20-25) from a downstream largely alpha-helical region. The current study demonstrates that the G26R variant promotes a structural transition of positions 27-56 to a mixture of coil and beta-strand secondary structure. Microscopy and staining by amyloidophilic dyes suggest that this alteration extends throughout the protein within 1 week of incubation in vitro, leading to insoluble aggregates of distinct morphology. The severe consequences of the Iowa mutation likely arise from the combination of losing the contribution of the native Gly residue in terminating beta-strand propagation and the promotion of beta-structure when an Arg is introduced adjacent to the succeeding residue of identical charge and size, Arg27.
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| 15. |
- Lings, Brian, et al.
(författare)
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Ten Strategies for Successful Distributed Development
- 2006
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Ingår i: The Transfer and Diffusion of Information Technology for Organizational Resilience. - Boston : Springer. - 0387344098 - 9780387344096 - 9780387344102 ; , s. 119-137
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Konferensbidrag (refereegranskat)abstract
- This paper presents an overview of the field of distributed development of software systems and applications (DD). Based on an analysis of the published literature, including its use in different industrial contexts, we provide a preliminary analysis that structures existing DD knowledge, indicating opportunities but identifying threats to communication, coordination, and control caused by temporal distance, geographical distance, and socio-cultural distance. An analysis of the case and field study literature has been used to identify strategies considered effective for countering the identified threats. The paper synthesizes from these a set of 10 general strategies for successful DD which, if adopted, should lead to increased company resilience.
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| 16. |
- Lundell, Björn, et al.
(författare)
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The distributed open source software development model : Observations on communication, coordination and control
- 2006
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Ingår i: Proceedings of the 14th European Conference on Information Systems, ECIS 2006. - : Göteborgs Universitet. ; , s. 1-12
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Konferensbidrag (refereegranskat)abstract
- There are many reasons why an organisation should consider adopting distributed development of software systems and applications, including access to a larger labour pool and a broader skills base, cost advantages, and round the clock working. However, distributed development presents many challenges stemming from the complexity of maintaining good communication, coordination and control when teams are dispersed in time (e.g. across time zones) and space, as well as socio-culturally. The open source software (OSS) development model is distributed by nature, and many OSS developments are considered success stories. The question therefore arises of whether traditional distributed development models can be improved by transfer of successful practice from OSS development models. In this paper we compare OSS with traditional distributed development models using a framework-based analysis of the extant literature. From our analysis we find that the advantages of temporal and geographical distance dominate in OSS, rather than their associated problems. Further, socio-cultural distance is lowered by active developer selection. However, there is a challenge to satisfying project goals when personal goals dominate.
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| 17. |
- Nyström, Henrik, 1977, et al.
(författare)
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Platelet-derived growth factor B retention is essential for development of normal structure and function of conduit vessels and capillaries
- 2006
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Ingår i: Cardiovasc Res. - : Oxford University Press (OUP). - 0008-6363. ; 71:3, s. 557-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Extracellular retention of PDGF-B has been proposed to play an important role in PDGF-B signalling. We used the PDGF-B retention motif knockout mouse (RetKO) to study the effects of retention motif deletion on development of micro- and macrovascular structure and function. METHODS: Passive and active properties of conduit vessels were studied using myograph techniques and histological examination. Capillary structure and function was studied using measurements of capillary density in skeletal muscle and by assessing aerobic physical performance in a treadmill setup. Cardiac function was assessed using echocardiography. RESULTS: Myograph experiments revealed an increased diameter and stiffness of the aorta in RetKO. Histological examination showed increased media collagen content and a decreased number of aortic wall layers, however with a similar number of vascular smooth muscle cells. This outward eutrophic remodelling of the aorta was accompanied by endothelial dysfunction. RetKO showed decreased capillary density in skeletal muscle and signs of a defective delivery of capillary oxygen to skeletal muscle, as shown by a decreased physical performance. In RetKO mice, echocardiography revealed an adaptive eccentric cardiac hypertrophy. CONCLUSION: We conclude that retention of PDGF-B during development is essential for a normal conduit vessel function in the adult mouse. Furthermore, PDGF-B retention is also necessary for the development of an adequate capillary density, and thereby for a normal oxygen delivery to skeletal muscle. The lack of primary effects on cardiac function supports the redundant role of PDGF-B in cardiac development.
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| 18. |
- Palmqvist, Niklas, 1974, et al.
(författare)
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Fibronectin-binding proteins and fibrinogen-binding clumping factors play distinct roles in staphylococcal arthritis and systemic inflammation
- 2005
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Ingår i: J Infect Dis. - 0022-1899. ; 191:5, s. 791-8
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a commonly encountered pathogen in humans, and it has the potential to cause destructive and life-threatening conditions, including septic arthritis. The pathogenicity of staphylococci depends on the expression of virulence factors. Among these, staphylococcal cell-surface proteins with tissue-adhesive functions have been suggested to mediate the colonization of host tissues, a crucial step in the establishment of infection. We investigated the relative contribution of the fibronectin-binding proteins (FnBPs) and fibrinogen-binding clumping factors (Clfs) to staphylococcal virulence in an experimental model of septic arthritis. The results show that these 2 sets of proteins play distinctly different roles in the development and progression of septic arthritis. Although Clfs significantly contributed to the arthritogenicity of S. aureus, FnBPs had no effect on the development of arthritis. Conversely, FnBPs played an important role in the induction of systemic inflammation, characterized by interleukin-6 secretion, severe weight loss, and mortality.
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