“
“Background Bacterial genomes appear as compact DNA masses, termed nucleoids, located centrally along both the length and width of the cells [1]. Nucleoids are highly organised structures within which each chromosome region occupies Selleck Luminespib specific locations along the length of the cell and displays a distinct choreography selleck screening library during the cell cycle (for reviews: [2,

3]). In most bacteria, nucleoids contain a single chromosome replicated from a single origin. This defines two oppositely oriented replichores, each extending from the replication origin, oriC to the terminal (ter) region, oppositely located on circular chromosomes. This replicative organisation has important consequences for the global organisation and segregation of bacterial nucleoids. In E. coli, replication occurs around the cell centre (i.e., the mid-cell position) [4]. Segregation is concomitant with replication so that replicated loci are segregated from mid-cell to the equivalent positions in the future daughter cells (the quarter positions) following the order of their replication [5–9]. The oriC region (ori) is thus the first to segregate, and the ter region the last. In newborn

cells, loci of the ter region are located close to the new cell pole (polar positioning) and migrate towards the midcell during the replication process. Recent advances Fosbretabulin mouse in bacterial cell cytology allow a general model of the check details E. coli nucleoid structure to be established. The ori region, located towards midcell, migrates to the quarter positions after being duplicated. The two replichores occupy distinct locations on each side of ori with chromosome loci recapitulating the ori-ter genetic map along the cell length axis [7, 10, 11]. In this model, the ter region is inferred to contain a stretched

region linking the two nucleoid edges [12, 13]. This linking region is believed to be composed of a segment of 50 kb randomly taken within the 400 kb ter region. Notably, the ter region is the site of specific activities involved in segregation [14, 15]: in particular, it interacts with the MatP protein [16] and with the FtsK DNA translocase ([17]; our unpublished results). In addition to this replichore organisation, the E. coli nucleoid appears to be structured into macrodomains (MDs). MDs are 0.5 to 1 Mb regions inferred to be self-compacted and composed of loci having similar intracellular positioning and dynamics during segregation [6, 9, 18]. The E. coli chromosome contains four MDs: the Ori and Ter MDs (containing ori and ter, respectively) and the Right and Left MDs flanking the Ter MD. The two regions flanking the Ori MD, called the non-structured regions (NS regions), do not display MD properties and contain loci displaying a higher intracellular mobility than MD-borne loci [9]. Most studies of the localization of chromosomal loci in bacteria have focused on their position along the length of the cell.

pneumoniae MGH78578, plasmid pMAS2027 (E. coli), plasmid pOLA52 (E. coli), plasmid pIA565 (K. pneumoniae), E. coli ECOR28, C. freundii M46, K. oxytoca M126, and C. koseri ATCC BAA895. The mrk genes are indicated in blue and include mrkE (putative regulatory gene), mrkA (major subunit encoding gene), mrkB (chaperone encoding gene), mrkC (usher encoding gene), mrkD (adhesin encoding gene) and mrkF (putative

minor subunit Fer-1 solubility dmso encoding gene). ORFs encoding putative transposable elements (yellow) and hypothetical proteins (grey) are indicated. The gene indicated in red (labelled cko_00966 and kpn_03274 in the genomes of C. koseri ATCC BAA895 and K. pneumoniae MGH78578, respectively) encodes a hypothetical protein containing a central EAL domain and was present downstream of mrkF in 29 strains. Sequence information TPCA-1 ic50 outside the mrk cluster is not known for K. pneumoniae pIA565. Arrows indicate the direction

of transcription for each gene. Type 3 fimbriae are functionally expressed in C. freundii, C. koseri, E. coli, K. oxytoca and K. pneumoniae All of the mrk-positive strains examined in this study mediated mannose-resistant hemagglutination of tannic acid treated human RBC (MR/K agglutination), KU55933 in vitro indicating they produced type 3 fimbriae. To specifically demonstrate a direct association between MR/K agglutination and type 3 fimbriae, the mrk locus was deleted from thirteen strains (E. coli MS2027, M184, ECOR15, ECOR28; K. pneumoniae M20, M124, M446, M542, M692; K. oxytoca M126, M239; C. freundii M46; C. koseri M546) employing λ-red mediated homologous recombination. The strains were selected on the basis of their transformation efficiency and included at least one representative from each of the mrk phylogenetic clades. Several different assays were employed to compare the thirteen sets of wild-type and mrk deletion strains. First, SDS-PAGE analysis of crude cell lysates

and Fluorouracil concentration subsequent Western blotting was performed using a type 3 fimbriae-specific antiserum. A predominant 15 kDa band representing the MrkA major subunit was detected from all wild-type strains except C. freundii M46, which failed to react positively in this assay. In contrast, no reaction was observed for any of the mrk deletion mutants (Fig. 3 and data not shown). Next, the wild-type and mrk mutant strains were compared for their ability to mediate MR/K agglutination. Only the wild-type strains produced a positive phenotype (Fig. 4 and data not shown). Finally, the presence of type 3 fimbriae was confirmed by immunogold labelling employing type 3 fimbriae-specific antiserum for E. coli ECOR15 and C. koseri M546, but was absent in their corresponding mrk deletion mutants (Fig. 5). Taken together, the results demonstrate that MR/K agglutination is a conserved phenotype for a range of Gram-negative organisms that express functional type 3 fimbriae. Figure 3 Western blot analysis employing type 3 fimbriae specific antiserum.

The Hawksworth (1991) estimate was established based on a ratio of plant:fungal species in temperate regions. Whether these ratios hold up in tropical AR-13324 manufacturer regions is indirectly assessed in the papers of Berndt (2012) and Mangelsdorff et al. (2012) with sometimes conflicting results, highlighting the value of both sound taxonomic and monographic treatments as well as the need for more long-term fungal studies in tropical regions. For instance, the rust fungi (obligate plant pathogens) may be the best documented group of microfungi, yet Berndt (2012) found that ratios of known rust:plant

species in Neotropical countries ranged from 1:16 to 1:124—no doubt a reflection, at least in part, of under sampling for fungi in most of these areas. Lücking (2012) asks the question of not just how many species remain to be discovered, but of what form these species may take. He uses a novel ‘character correlation index’ whereby combinations of traits that are known to be correlated in currently described species are used to predict the traits that find more are expected to be correlated and found in currently unknown species. He predicts that another 48 lichen-forming fungi in the Graphis group alone remain to be discovered, approximately doubling the

known number in this genus. The impacts of disturbances on fungal communities have been poorly studied in tropical regions, perhaps because these communities have been BI-D1870 cost considered, likely wrongly, as both resistant and resilient to disturbance (Allison and Martiny 2008). Three papers in this issue address selleck products this assumption: da Silva et al. (2012) determine the impact of mining and restoration in Brazilian restinga on communities of arbuscular mycorrhizal fungi by counting and identifying spores. Hattori et al. (2012) show how diversity of polypore fungi is

dependent upon the presence of suitable host trees that may be removed by logging or conversion to plantations in their Malaysian study sites. And, as already discussed, López-Quintero et al. (2012) examine the effects of clearance for shifting cultivation and subsequent forest recovery on fungal diversity. Just as the study of Berndt (2012) shows that species data is unevenly distributed geographically, other papers in this issue show that there are, likewise, a number of specialized habitats that still remain to be fully assessed for tropical fungal diversity. These include fungi inhabiting insect guts, among which are Trichomycetes that have been reviewed by Lichtwardt (2012). The abundance and diversity of insect host species will clearly affect fungal species diversity and an improved assessment of insect-associated fungal diversity in the tropics is certainly a priority for mycologists. Finally, Jones and Pang (2012) provide a timely review of tropical aquatic fungi, highlighting areas in need of future research.

With increasing thickness of the Ag surface layer, the average transmittance of the multilayer films first increases then decreases. Compared with the bare ITO films, the absorption of multilayer films increases due to the introduction of a double Ag layer. However, the absorption of Ag1/ITO/Ag film is close to that of the bare ITO film, selleck chemicals llc and no absorption peaks appeared.

Figure 7 Optical absorption spectra of the ITO and Ag/ITO/Ag multilayer films. Conclusions Ag/ITO/Ag multilayer films with different thicknesses of the surface Ag layer were prepared by magnetron sputtering on a glass substrate. Microstructural LY2874455 nmr analysis shows that the multilayer films have a polycrystalline structure. As the thickness of the Ag surface layer increases, the preferred orientation of Ag (111) intensified. With increasing thickness of Ag surface layer, the transmittance spectra and reflectance spectra of Ag/ITO/Ag multilayer films decrease and increase, respectively. Ag3/ITO/Ag multilayer

film shows the best comprehensive property and can be used as a potential transflective candidate in future LCD. Acknowledgements This work is supported by the National Natural Science Foundation of China (nos. 51072001 and 51272001), National Key Basic Research Program GDC-0941 cost (973 Project) (2013CB632705), and the National Science Research Foundation for Scholars Return from Overseas, Ministry of Education, China. The authors would like to thank Yonglong Zhuang and Zhongqing Lin of the Experimental Technology Center of Anhui University for the electron microscope test and discussion. References 1. Bhatti MT, Rana AM, Khan AF: Characterization of rf-sputtered indium tin oxide thin films. Mater Chem Phys Inositol oxygenase 2004, 84:126.CrossRef 2. Dawar AL, Joshi JC:

Semiconducting transparent thin films: their properties and applications. J Mater Sci-Mater M 1984, 19:1.CrossRef 3. Meng LJ, Placido F: Annealing effect on ITO thin films prepared by microwave-enhanced dc reactive magnetron sputtering for telecommunication applications. Surf Coat Tech 2003, 166:44.CrossRef 4. Deng W, Ohgi T, Nejo H: Development of conductive transparent indium tin oxide (ITO) thin films deposited by direct current (DC) magnetron sputtering for photon-STM applications. Appl Phys A-Mater 2001, 72:595.CrossRef 5. Chopra KL, Major S, Pandya DK: Transparent conductors-A status review. Thin Solid Films 1983, 102:1.CrossRef 6. Cui HN, Xi SQ: The fabrication of dipped CdS and sputtered ITO thin films for photovoltaic solar cells. Thin Solid Films 1996, 288:325.CrossRef 7. Miedziński R, Ebothé J, Kozlowski G, Kasperczyk J, Kityk IV: Laser induced microrelief superstructure of Ag/ITO seed-mediated nanocomposites. Superlattice Microst 2009, 46:637.CrossRef 8. Choi KH, Kim JY, Lee YS, Kim HJ: ITO/Ag/ITO multilayer films for the application of a very low resistance transparent electrode. Thin Solid Films 1999, 341:152.CrossRef 9.

The structure, surface morphology, composition, and optical properties of ZnO/GaN/Si thin films were

investigated by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), infrared (IR) absorption spectra, and photoluminescence (PL) spectra. Methods Samples and measurements First, GaN thin films were grown on Si (111) substrate by PLD at the growth temperature of 800°C using a GaN ceramic target. The film deposition was carried out in a stainless steel vacuum chamber evacuated by a turbomolecular pump to a base pressure of 5.6 × 10−5 Pa. A pulsed Nd:YAG laser with a wavelength of 1,064 nm (repetition 10 Hz, duration 10 ns) was focused by a lens on the ZnO target at an angle of incidence of 45°. During the deposition, the laser incident energy was maintained at 300 mJ/pulse. The size of the ablation spot is about 0.5 mm in diameter. Thiazovivin manufacturer A series of Si (111) substrate was placed at 40 mm from the target surface. For the ZnO target ablation and even thin film fabrication, GaN target and substrate rotated reversely with a frequency of 7 rpm. GaN films were deposited in the nitrogen background of 1.3 Pa, and depositing time was 15 min. The thickness of GaN thin films measured RG7112 research buy is about 50 nm. Second, the samples were placed on a quartz carrier and annealed in

a high-temperature tube quartz furnace. After the furnace reached the equilibrium temperature of 1,000°C the

carrier with the GaN samples was placed in a constant temperature region of the furnace. Flowing N2 was introduced into the tube for 5 min at a flow rate of 100 ml/min to flush out the residual air. Then, we terminated N2 flow and introduced NH3 into the tube at a flow rate of Fossariinae 800 ml/min for 20 min. Finally, the NH3 was flushed out by N2 introduced into the tube for another 5 min before the carrier was removed from the furnace. Third, ZnO thin films were fabricated on GaN (111) template by PLD at a growth temperature of 400°C in O2 ambience with a pressure of 1.3 Pa using a ZnO ceramic target. The laser incident energy was maintained at 200 mJ/pulse, and depositing time was 60 min. The thickness of ZnO thin films is about 600 nm, which was measured by the weight technique. The structural properties of thin films were studied by Rigaku D/max-rB XRD (Tokyo, Japan) spectroscopy with Cu Kα line radiation at 0.15418 nm. The surface morphology and the microstructure were studied using FESEM (QUANTA 250, FEI Co., Hillsboro, OR, USA). The IR buy NVP-BSK805 spectra were acquired using a BRUKER TENSOR27 spectrophotometer (Bruker Optik Gmbh, Ettlingen, Germany; wavenumber range 400 to 4,000 cm−1, optical resolution 4 cm−1, transmission mode). The optical properties of ZnO thin films were characterized by photoluminescence spectra with the excitation wavelength of 320 nm pumped by Xe lamp.

U) 7.083 2.576-14.621 #selleck compound randurls[1|1|,|CHEM1|]# <0.0001 4.739 1.872-12.053 <0.0001 Age (>65 vs. ≦65) 1.241 0.768-5.724 0.7931       Sex (Male vs. Female) 0.926 0.753-3.761 0.8541       Number (Multiple vs. Single) 1.411 0.674-12.653 0.7244       Size (>3 cm vs. ≤3 cm) 1.537 0.687-10.431 0.7196       Grade (G3 vs. G1/G2) 5.067 1.933-10.763 0.0006 2.055 1.644-8.431 0.0137 Stage (T1 vs. Ta) 2.073 1.027-9.754 0.0176 1.371 0.824-6.084 0.0735 HR: Hazard Ratio; M: Methylated; U: unmethylated. Table 4 The predictive value of PCDH8 methylation for the progression-free survival in non muscle invasive bladder cancer (n = 233) Variable Univariate analysis Multivariate analysis HR 95% CI P HR 95% CI P PCDH8 methylation

(M vs. U) 4.893 1.872-9.433 RG7112 supplier <0.0001 2.523 1.654-7.431 0.0036 Age (>65 vs. ≦65) 0.896 0.873-5.215 0.8614       Sex (Male vs. Female) 1.213 0.855-5.217 0.5461       Number (Multiple vs. Single) 1.322 0.729-8.537 0.4668       Size (>3 cm vs. ≤3 cm) 1.227 0.579-11.460 0.4962       Grade (G3 vs. G1 / G2) 3.679 1.463-7.754 0.0017 1.874 1.237-6.873 0.0233 Stage (T1 vs. Ta) 1.625 0.893-6.792 0.0614       HR: Hazard Ratio; M: Methylated; U: Unmethylated.

Table 5 The predictive value of PCDH8 methylation for the five-year overall survival in non muscle invasive bladder cancer (n = 233) Variable Univariate analysis Multivariate analysis HR 95% CI P HR 95% CI P PCDH8 methylation (M vs. U) 4.653 1.237-7.314 <0.0001 3.017 1.542-8.251 0.0015 Age (>65 vs. ≦65) 1.135 0.779-6.273 0.3471       Sex (Male vs. Female) 0.874 0.645-3.228 0.7361       Number (Multiple vs. Single) 1.054 0.798-6.417 0.3784       Size (>3 cm vs. ≤3 cm)

1.253 0.913-10.257 0.3095       Grade (G3 vs. G1 / G2) 3.876 1.643-6.024 0.0021 1.852 1.144-5.964 0.0324 Stage (T1 vs. Ta) 1.015 0.792-7.572 0.4338 Nutlin-3 datasheet       HR: Hazard Ratio; M: Methylated; U: Unmethylated. Discussion Bladder cancer is a multifaceted disease with clinical outcome difficult to predict, and the morphological similar tumors can behave differently [2]. Thus, new biomarkers are needed to predict the outcome of bladder cancer, in addition to commonly used clinicopathological parameters [2]. In recent years, more and more researchers are interested in the aberrant methylation of different genes in bladder cancer for some reasons [9,10,26]. Firstly, aberrant methylation in the promoter regions of the tumor suppressor genes at CPG islands has been recognized as one of the hallmarks of human cancers and associated with silence of gene expression, which may be used as potential biomarker in human cancers [27-31]. Secondly, DNA methylation can be reversed by demethylating agents, which may used as effective therapeutic target. PCDH8 is a novel tumor suppressor gene, and commonly inactivated by aberrant promoter methylation in human cancers [11-16].

(d) The Ag-Ag bond. Conclusions E-beam evaporation with IAD has been applied to produce TAS layers with favorable properties: the sheet resistivity of the obtained material was 6.5 Ω/sq and its average transmittance (400 to 700 nm) was 89%. Environmental testing under high temperature and humidity conditions demonstrated that the amorphous SiO2 layer was stable and could avoid silver Fer-1 nmr oxidation and vulcanization. The resulting thickness and structure of the Ag layer were the main factors determining the electrical and optical properties of the multilayer structures. According

to the results of both optical design and simulations, the first layer was fabricated using a high-reflection-index material, whereas the last layer was fabricated using a low-reflection-index material. This structure was introduced to maximize the average transmittance of visible light. Acknowledgements The authors this website would like to thank the National Science Council of the ROC, Taiwan (contract no. 102-2622-E-492 -018 -CC3) for financially supporting this research. References 1. Leftheriotis G, Papaefthimou S, Yianoulis P: Development

of multilayer transparent conductive coatings. Solid State Ion 2000, 136–137:655–661.CrossRef Selleckchem KU55933 2. Chiu PK, Cho WH, Chen HP, Hsiao CN, Yang JR: Study of a sandwich structure of transparent conducting oxide films prepared by electron beam evaporation at room temperature. Nanoscale Res Lett 2012, 7:304–308.CrossRef 3. Kusano E, Kawaguchi J, Enjouji K: Thermal stability of heat-reflective films consisting of oxide–Ag–oxide deposited by dc magnetron sputtering. J Vac Sci Technol A 1986, 4:2907–2910.CrossRef 4. Bender M, Seelig W, Daube C, Frankenberger H, Ocker B, Stollemwerk J: Intense visible photoluminescence from coloured

LiF films on silicon. Thin Sol Films 1998, 326:67–69.CrossRef 5. Chiba K, Nakatani K: Photoenhance migration of silver atoms in transparent heat mirror coatings. Thin Sol Films 1984, 112:359–367.CrossRef 6. Dima I, Popescu B, Iova F, Popescu G: Influence of the silver layer on the optical properties of the TiO 2 /Ag/TiO 2 multilayer. Thin Sol Films 1991, 200:11–18.CrossRef Fluorouracil molecular weight 7. Bender M, Seelig W: Dependence of film composition and thicknesses on optical and electrical properties of ITO-metal-ITO multilayers. Thin Sol Films 1998, 326:67–71.CrossRef 8. Kloppe , Scharmann A: Dependence of the electrical and optical behaviour of ITO-silver-ITO multilayers on the silver properties. Thin Sol Films 2000, 365:139–146.CrossRef 9. Lewis J, Grego S: Highly flexible transparent electrodes for organic light-emitting diode-based displays. Appl Phys Lett 2004, 85:3450–3452.CrossRef 10. Kim SW, Shin YW: The effect of the amorphous insulator layer on conduction behaviors of the silica/indium tin oxide two-layer films. Thin Sol Films 2003, 437:242–247.CrossRef 11.

BLAST PF-01367338 supplier results were parsed and filtered using a custom Perl script with the above criteria. The Perl script also mapped the hits to the corresponding COG category, reporting the category or categories for each query sequence. Each set was analysed 1,000 times randomly sampling 75% of the query sequences to calculate the Standard Deviation (SD; Figure 1). For the characterization of OGs, each comprising one gene per genome, only genes present in the genome of X. euvesicatoria str. 85-10 were used as representative

of the OG. Taxonomical distribution of homologous sequences BLAST searches against the non-redundant protein database of the NCBI (NR) [87] were performed in order to

identify Selleckchem MK-1775 the homologs of one QNZ order or more genes in other organisms, with default parameters and Expect value below 10-10. The BLAST result was subsequently parsed with a custom Perl script to extract the organisms, subsequently building a cumulative counts table and mapping these organisms to any fixed taxonomical level using the NCBI’s Taxonomy database [87]. Acknowledgements This project was funded by the Colombian administrative department of Science, Technology and Innovation (Colciencias) and the Vice-chancellor’s Office of Research at the Universidad de Los Andes. We would like to thank Andrew Crawford, Ralf Koebnik and two anonymous reviewers for critical reading of the manuscript. We also thank Boris Szurek, Valérie Verdier, Kostantinos Konstantinidis, Catalina Arévalo and Camilo López for comments and discussion enough on the conception

and development of this study. Electronic supplementary material Additional file 1: COG distribution of different taxonomical ranges. Raw data graphically presented in Figure 2. Each row corresponds to one COG functional category. Each taxonomical range is represented in two columns, the average and the standard deviation. (PDF 23 KB) Additional file 2: Concatenated sequence alignment and partitions. ZIP file containing the input alignment in Phylip format (Suppl_file_2.phylip) and the coordinates of the partitions (Suppl_file_2.raxcoords) as employed for the ML phylogenetic analysis in RAxML. Unus automatically generated these files. (ZIP 2 MB) Additional file 3: Leaf and ancestral nodes in the GenoPlast events matrix. Each row corresponds to one node, and each column corresponds to a pattern of regions, as defined by Mauve developers’ tools. The first two additional columns contain the node identifier and the node content. (CSV 598 KB) Additional file 4: Species counts in similar sequences of cluster 1. Species counts within the BLAST hits in NCBI’s NR using the genes of Xeu8 in the cluster as query. (PDF 25 KB) Additional file 5: Species counts in similar sequences of cluster 2.

Conflicts of interest None. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. Appendix 1 Table 5 List of ICD-10 CA codes by type of fracture Fracture type ICD 10 codes relating to fracture KU55933 order type Hip S72.0, S72.1, S72.2 Humerus S42.2 Vertebral S22.0, S22.1, S32.0 Wrist S52 with CCI codes Other sites:

 • Femur S72.3, S72.4, S72.7, S72.8, S72.9  • Lower leg (tibia, fibula, ankle, knee, foot) S82.0–S82.9, S92  • Lower arm (radius, ulna) S52 unless wrist above  • Other site (rib, shoulder, arm) S22.3, S42.0, S42.7, S42.8, S42.9  • Other fractures including: S22.2, S22.4,

S22.8, S22.9  • ribs/sternum, clavicle, pelvis, patella, S32.1, S32.3, S32.4, S32.5, S32.7, S32.8  • tibia/fibula, ankle S42.0–42.9 except 42.2, S42.7, S42.8, Ilomastat order S42.9 S72.0–72.9 except when “hip/femur” from above Multiple fractures T02.1–T02.9 (or more than 1 of above) References 1. Papaioannou A, Morin S, Cheung AM, Atkinson S, Brown JP, Feldman S, Hanley DA, Hodsman A, Jamal SA, Kaiser SM et al (2010) 2010 clinical Belnacasan concentration practice guidelines for the diagnosis and management of osteoporosis in Canada: summary. CMAJ 182(17):1864–1873PubMedCrossRef 2. Brown JP, Josse RG (2002) 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 167(10 Suppl):S1–S34PubMed 3. Statistics Canada (2010) Estimates of population, by age group and sex for July 1, Canada, provinces and territories, annual. Table 051–0001

4. Goeree R, O’Brien B, Pettitt D, Cuddy L, Ferraz M, Adachi JD (1996) An assessment of the burden of illness due to osteoporosis in Canada. J Soc Obstet Gynaecol Can 18(Suppl July):15–24 5. Statistics Canada (2011) Consumer Price Index (CPI) Statistics. Table 176–000 6. Canadian Institute for Health Information (2006) Discharge Abstract Database (DAD) Abstracting Manual, 2007–2008 Edition (Ottawa: CIHI, 2006) 7. Canadian Institute for Health Information (2010) National selleck chemicals llc Ambulatory Care Reporting System (NACRS), Database Background and General Data Limitations Documentation,, 2007–2008 (Ottawa, Ont.: CIHI, 2008) 8. Canadian Institute for Health Information (2010) National Rehabilitation Reporting System (NRS) Data Quality Documentation 2007–2008 (Ottawa, Ont.: CIHI, 2009) 9. Canadian Institute for Health Information (2010) Home Care Reporting System 10. Canadian Institute for Health Information (2010) Continuing Care Reporting System (CCRS) Specifications Manual, 2009 (Ottawa, Ont.: CIHI, 2008) 11. Intercontinental Marketing Services (IMS) Health Canada (2010) 12. IMS Brogan (2010) Brogan PharmaStat ® Database. Pharmaceutical Market Data 13.

The local networks thus established were called Biocentres. The recent establishment of a competitive State subsidy funding system (EVO-funding) has also provided university clinics with additional funding for clinical research and training of physicians (Academy of Finland 2009). However, public sector reforms in the 1990s have decentralized competences towards municipalities (regional authorities), giving these authorities an internationally unprecedented level of competence and financial responsibility

for health policy (Hakkinen and Lehto 2005). These municipalities have in turn had a tendency to take find more funds earmarked for research to finance clinical care (Academy of Finland 2009; The Science and Technology Policy Council of Finland 2008; Visakorpi 2009). So while the Finnish academic medical research sector seems to be facing institutional obstacles to the conduct of TR work, recent policy discussions have taken up the arguments of the TR narrative in efforts to reform local clinical research infrastructures. Germany The Translational Research Alliance in Lower-Saxony (TRAIN) offers an interesting mTOR inhibitor case to illustrate the development of TR activities in Germany. The initiative is explicitly

concerned with developing new compounds. This aim is check details explicitly carried over in the shape of the collaboration and the members it includes. TRAIN regroups seven partners that STK38 all directly take part in various tasks and work packages of the collaboration’s projects. These institutes are located in relative proximity within the two largest cities of the region. Founding members

of the consortium are the Gottfried Wilhelm Leibniz Universität Hannover, the Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), the Hannover Medical School (MHH), the Helmholtz Centre for Infection Research (HZI), the Technische Universität Carolo-Wilhelmina zu Braunschweig and the University of Veterinary Medicine Hannover. An additional member of the consortium is the life sciences project management firm VPM. These founding members have launched a number of joint ventures that act as additional members of the consortium, including: Twincore, which brings together researchers from the Helmholtz Centre for Infection Research with large laboratory equipment for analyzing pharmaceutically active substances with clinicians and laboratory scientists with a clinical background from the nearby Hannover Medical School; the Centre for Biomolecular Drug Research, a screening and drug development facility and the forthcoming Clinical Research Center, linking capacities for early clinical trials to pre-clinical laboratory facilities.