Empirical comparison of high gradient achievement for different metals in DC and pulsed mode

For the SwissFEL project, an advanced high gradient low emittance gun is under development. Reliable operation with an electric field, preferably above 125 MV/m at a 4 mm gap, in the presence of an UV laser beam, has to be achieved in a diode configuration in order to minimize the emittance dilution due to space charge effects. In the first phase, a DC breakdown test stand was used to test different metals with different preparation methods at voltages up to 100 kV. In addition high gradient stability tests were also carried out over several days in order to prove reliable spark-free operation with a minimum dark current. In the second phase, electrodes with selected materials were installed in the 250 ns FWHM, 500 kV electron gun and tested for high gradient breakdown and for quantum efficiency using an ultra-violet laser.Comment: 25 pages, 13 figures, 5 tables. Follow up from FEL 2008 conference (Geyongju Korea 2008) New Title in JVST A (2010) : Vacuum breakdown limit and quantum efficiency obtained for various technical metals using DC and pulsed voltage source

Quantitative and molecular genetics of juvenile wood traits in radiata and slash/Caribbean pines.

The Juvenile Wood Initiative (JWI) project has been running successfully since July 2003 under a Research Agreement with FWPA and Letters of Association with the consortium partners STBA (Southern Tree Breeding Association), ArborGen and FPQ (Forestry Plantations Queensland). Over the last five and half years, JWI scientists in CSIRO, FPQ, and STBA have completed all 12 major milestones and 28 component milestones according to the project schedule. We have made benchmark progress in understanding the genetic control of wood formation and interrelationships among wood traits. The project has made 15 primary scientific findings and several results have been adopted by industry as summarized below. This progress was detailed in 10 technical reports to funding organizations and industry clients. Team scientists produced 16 scientific manuscripts (8 published, 1 in press, 2 submitted, and several others in the process of submission) and 15 conference papers or presentations. Primary Scientific Findings. The 15 major scientific findings related to wood science, inheritance and the genetic basis of juvenile wood traits are: 1. An optimal method to predict stiffness of standing trees in slash/Caribbean pine is to combine gravimetric basic density from 12 mm increment cores with a standing tree prediction of MoE using a time of flight acoustic tool. This was the most accurate and cheapest way to rank trees for breeding selection for slash/Caribbean hybrid pine. This method was also recommended for radiata pine. 2. Wood density breeding values were predicted for the first time in the STBA breeding population using a large sample of 7,078 trees (increment cores) and it was estimated that selection of the best 250 trees for deployment will produce wood density gains of 12.4%. 3. Large genetic variation for a suite of wood quality traits including density, MFA, spiral grain, shrinkage, acoustic and non-acoustic stiffness (MoE) for clear wood and standing trees were observed. Genetic gains of between 8 and 49% were predicted for these wood quality traits with selection intensity between 1 to 10% for radiata pine. 4. Site had a major effect on juvenile-mature wood transition age and the effect of selective breeding for a shorter juvenile wood formation phase was only moderate (about 10% genetic gain with 10% selection intensity, equivalent to about 2 years reduction of juvenile wood). 5. The study found no usable site by genotype interactions for the wood quality traits of density, MFA and MoE for both radiata and slash/Caribbean pines, suggesting that assessment of wood properties on one or two sites will provide reliable estimates of the genetic worth of individuals for use in future breeding. 6. There were significant and sizable genotype by environment interactions between the mainland and Tasmanian regions and within Tasmania for DBH and branch size. 7. Strong genetic correlations between rings for density, MFA and MoE for both radiata and slash/Caribbean pines were observed. This suggests that selection for improved wood properties in the innermost rings would also result in improvement of wood properties in the subsequent rings, as well as improved average performance of the entire core. 8. Strong genetic correlations between pure species and hybrid performance for each of the wood quality traits were observed in the hybrid pines. Parental performance can be used to identify the hybrid families which are most likely to have superior juvenile wood properties of the slash/Caribbean F1 hybrid in southeast Queensland. 9. Large unfavourable genetic correlations between growth and wood quality traits were a prominent feature in radiata pine, indicating that overcoming this unfavourable genetic correlation will be a major technical issue in progressing radiata pine breeding. 10. The project created the first radiata pine 18 k cDNA microarray and generated 5,952 radiata pine xylogenesis expressed sequence tags (ESTs) which assembled into 3,304 unigenes. 11. A total of 348 genes were identified as preferentially expressed genes in earlywood or latewood while a total of 168 genes were identified as preferentially expressed genes in either juvenile or mature wood. 12. Juvenile earlywood has a distinct transcriptome relative to other stages of wood development. 13. Discovered rapid decay of linkage disequilibrium (LD) in radiata pine with LD decaying to approximately 50% within 1,700 base pairs (within a typical gene). A total of 913 SNPS from sequencing 177,380 base pairs were identified for association genetic studies. 14. 149 SNPs from 44 genes and 255 SNPs from a further 51 genes (total 95 genes) were selected for association analysis with 62 wood traits, and 30 SNPs were shortlisted for their significant association with variation of wood quality traits (density, MFA and MoE) with individual significant SNPs accounting for between 1.9 and 9.7% of the total genetic variation in traits. 15. Index selection using breeding objectives was the most profitable selection method for radiata pine, but in the long term it may not be the most effective in dealing with negative genetic correlations between wood volume and quality traits. A combination of economic and biological approaches may be needed to deal with the strong adverse correlation

The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation

The growth regulating factor CTGF/CCN-2 is an integral factor in growth and development, connective tissue maintenance, wound repair and cell cycle regulation. It has recently been reported that CTGF/CCN-2 is involved in very early development having been detected in early notochord formation in zebrafish using CTGF/CCN-2 promoter-driven green fluorescent protein (GFP) plasmids. In these studies fluorescence was detected early in the developing embryos, a finding of considerable significance in that CTGF/CCN-2 deficient mutant mice die early after birth due to severe cartilage and skeletal dysplasia and respiratory failure. Such findings confirm the importance of CTGF/CCN-2 in development and of the necessary and sufficient role of this molecule in formation of the skeleton, extracellular matrix and chondrogenesis. Of particular relevance to the relationship between the notochordal cell and CTGF/CCN-2 there is a remarkable sub-species of canine, the ‘non-chondrodystrophic’ canine that is protected from developing degenerative disc disease (DDD). These animals are unique in that they preserve the population of notochordal cells within their disc nucleus (NP) and these cells secrete CTGF/CCN-2. We have detected CTGF/CCN-2 within conditioned medium developed from the notochordal cells of these animals (NCCM) and used this conditioned medium to demonstrate robustly increased proteoglycan production. The addition of recombinant human CTGF/CCN-2 to totally serum-free media containing cultures of bovine NP cells replicated the robustly increased aggrecan gene expression found with NCCM alone strongly suggesting the importance of the effect of CTGF/CCN-2 in notochordal cell biology within the disc nucleus of non-chondrodystrophic canines. The chondrodystrophic canine, another sub-species on the other hand are almost totally devoid of notochordal cells and they develop DDD profoundly and early. These two sub-species of canine reflect a naturally occurring animal model that is an excellent example of differential notochordal cell survival and possible associated developmental differences in extracellular maintenance

CCN3 and bone marrow cells

CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a new antibody although they are a very few populations. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found its preference for osteogenic differentiation. From the analyses of in vitro experiment using an osteogenic mesenchymal stem cell line, Kusa-A1, we found that CCN3 downregulates osteogenesis by two different pathways; suppression of BMP and stimulation of Notch. Secreted CCN3 from Kusa cells inhibited the differentiation of osteoblasts in separate culture, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells

The role of CCN2 in cartilage and bone development

CCN2, a classical member of the CCN family of matricellular proteins, is a key molecule that conducts cartilage development in a harmonized manner through novel molecular actions. During vertebrate development, all cartilage is primarily formed by a process of mesenchymal condensation, while CCN2 is induced to promote this process. Afterwards, cartilage develops into several subtypes with different fates and missions, in which CCN2 plays its proper roles according to the corresponding microenvironments. The history of CCN2 in cartilage and bone began with its re-discovery in the growth cartilage in long bones, which determines the skeletal size through the process of endochondral ossification. CCN2 promotes physiological developmental processes not only in the growth cartilage but also in the other types of cartilages, i.e., Meckel’s cartilage representing temporary cartilage without autocalcification, articular cartilage representing hyaline cartilage with physical stiffness, and auricular cartilage representing elastic cartilage. Together with its significant role in intramembranous ossification, CCN2 is regarded as a conductor of skeletogenesis. During cartilage development, the CCN2 gene is dynamically regulated to yield stage-specific production of CCN2 proteins at both transcriptional and post-transcriptional levels. New functional aspects of known biomolecules have been uncovered during the course of investigating these regulatory systems in chondrocytes. Since CCN2 promotes integrated regeneration as well as generation (=development) of these tissues, its utility in regenerative therapy targeting chondrocytes and osteoblasts is indicated, as has already been supported by experimental evidence obtained in vivo

Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

<p>Abstract</p> <p>Background</p> <p>We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN) hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid) and poly-(N, N'-Dimetyl acrylamide), at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage.</p> <p>Methods</p> <p>We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations.</p> <p>Results</p> <p>The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes.</p> <p>Conclusions</p> <p>The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.</p

Exposure to depleted uranium does not alter the co-expression of HER-2/neu and p53 in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Amongst the extensive literature on immunohistochemical profile of breast cancer, very little is found on populations exposed to a potential risk factor such as depleted uranium. This study looked at the immunohistochemical expression of HER-2/neu (c-erbB2) and p53 in different histological types of breast cancer found in the middle Euphrates region of Iraq, where the population has been exposed to high levels of depleted uranium.</p> <p>Findings</p> <p>The present investigation was performed over a period starting from September 2008 to April 2009. Formalin-fixed, paraffin-embedded blocks from 70 patients with breast cancer (62 ductal and 8 lobular carcinoma) were included in this study. A group of 25 patients with fibroadenoma was included as a comparative group, and 20 samples of normal breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB+) complex method was employed for immunohistochemical detection of HER-2/neu and p53.</p> <p>The detection rate of HER-2/neu and p53 immunohistochemical expression were 47.14% and 35.71% respectively in malignant tumors; expression was negative in the comparative and control groups (p < 0.05).</p> <p>HER-2/neu immunostaining was significantly associated with histological type, tumor size, nodal involvement, and recurrence of breast carcinoma (<it>p </it>< 0.05), p53 immunostaining was significantly associated with tumor size, nodal involvement and recurrence of breast cancer (<it>p </it>< 0.05). There was greater immunoexpression of HER-2/neu in breast cancer in this population, compared with findings in other populations.</p> <p>Both biomarkers were positively correlated with each other. Furthermore, all the cases that co-expressed both HER-2/neu and p53 showed the most unfavorable biopathological profile.</p> <p>Conclusion</p> <p>P53 and HER-2/neu over-expression play an important role in pathogenesis of breast carcinoma. The findings indicate that in regions exposed to high levels of depleted uranium, although p53 and HER-2/neu overexpression are both high, correlation of their expression with age, grade, tumor size, recurrence and lymph node involvement is similar to studies that have been conducted on populations not exposed to depleted uranium. HER-2/neu expression in breast cancer was higher in this population, compared with results on non-exposed populations.</p

Normal growth and development in mice over-expressing the CCN family member WISP3

Loss-of-function mutations in the gene WISP3 cause the autosomal recessive human skeletal disease Progressive Pseudorheumatoid Dysplasia, whereas mice with knockout mutations of Wisp3 have no phenotype. The lack of a phenotype in the Wisp3 knockout mice has constrained studies of the protein’s in vivo function. Over-expression experiments in zebrafish indicated that WISP3 may function as a BMP and Wnt signaling modulator. To determine whether these biologic activities are retained in mice, we created two strains of transgenic mice that over-express WISP3 in a broad array of tissues. Despite strong and persistent protein over-expression, the transgenic mice remained phenotypically indistinguishable from their non-transgenic littermates. Surprisingly, WISP3 contained in conditioned medium recovered from transgenic mouse primary kidney cell cultures was able to bind BMP and to inhibit BMP signaling in vitro. Factors that account for the difference between the in vitro and in vivo activities of WISP3 remain unknown. At present, the mouse remains a challenging model organism in which to explore the biologic function of WISP3

The Wiring Economy Principle: Connectivity Determines Anatomy in the Human Brain

Minimization of the wiring cost of white matter fibers in the human brain appears to be an organizational principle. We investigate this aspect in the human brain using whole brain connectivity networks extracted from high resolution diffusion MRI data of 14 normal volunteers. We specifically address the question of whether brain anatomy determines its connectivity or vice versa. Unlike previous studies we use weighted networks, where connections between cortical nodes are real-valued rather than binary off-on connections. In one set of analyses we found that the connectivity structure of the brain has near optimal wiring cost compared to random networks with the same number of edges, degree distribution and edge weight distribution. A specifically designed minimization routine could not find cheaper wiring without significantly degrading network performance. In another set of analyses we kept the observed brain network topology and connectivity but allowed nodes to freely move on a 3D manifold topologically identical to the brain. An efficient minimization routine was written to find the lowest wiring cost configuration. We found that beginning from any random configuration, the nodes invariably arrange themselves in a configuration with a striking resemblance to the brain. This confirms the widely held but poorly tested claim that wiring economy is a driving principle of the brain. Intriguingly, our results also suggest that the brain mainly optimizes for the most desirable network connectivity, and the observed brain anatomy is merely a result of this optimization