Evaluation of Open Geospatial Consortium Standards fur Use In LLNL Geographic Information Systems (GIS)

The objective of this project is to evaluate existing and emerging Open Geospatial Consortium (OGC) standards for use in LLNL programs that rely heavily on geographic data. OGC standards are intended to facilitate interoperability between geospatial processing systems to avoid duplication of effort, lower development costs, and encourage competition based on improved capability and performance rather than vendor lock-in. Some of these standards appear to be gaining traction in the geospatial data community, the Federal government, DOE and DHS. A serious evaluation of this technology is appropriate at this time due to increasing interest and mandated compliance in the Federal government in some situations. A subset of OGC standards is identified and reviewed with a focus on applications to LLNL programs. Each standard or recommendation reviewed was evaluated in general terms. In addition, for specific programs such as Gen&SIS and NARAC, a specific evaluation was made of several of the standards and how they could be used most effectively. It is also important to evaluate the acceptance of these standards in the commercial arena. The implementation of OGC standards by the largest GIS vendor (ESRI) was reviewed. At present, OGC standards are primary useful in specific situations. More generally, many of the standards are immature and their impact on the government and commercial sectors is unclear. Consequently, OGC and related developments need to be observed. As specific standards or groups of standards mature and establish their relevance, these can also be incorporated in LLNL programs as requirements dictate, especially if open implementations and commercial products are available

Engineered Osteochondral Grafts Using Biphasic Composite Solid Free-Form Fabricated Scaffolds

Tissue engineering has provided an alternative to traditional strategies to repair cartilage damaged by injury or degenerative disease. A successful strategy to engineer osteochondral tissue will mimic the natural contour of the articulating surface, achieve native mechanical properties and functional load-bearing ability, and lead to integration with host cartilage and underlying subchondral bone. Image-based design (IBD) and solid free-form (SFF) fabrication can be used to generate scaffolds that are load bearing and match articular geometry. The objective of this study was to utilize materials and biological factors in an integrated approach to regenerate a multitissue interface. Biphasic composite scaffolds manufactured by IBD and SFF fabrication were used to simultaneously generate bone and cartilage in discrete regions and provide for the development of a stable interface between cartilage and subchondral bone. Poly-L-lactic acid/hydroxyapatite composite scaffolds were differentially seeded with fibroblasts transduced with an adenovirus expressing bone morphogenetic protein 7 (BMP-7) in the ceramic phase and fully differentiated chondrocytes in the polymeric phase. After subcutaneous implantation into mice, the biphasic scaffolds promoted the simultaneous growth of bone, cartilage, and a mineralized interface tissue. Within the ceramic phase, the pockets of tissue generated included blood vessels, marrow stroma, and adipose tissue. This combination of IBD and SFF-fabricated biphasic scaffolds with gene and cell therapy is a promising approach to regenerate osteochondral defects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63145/1/ten.2004.10.1376.pd

Evaluation of OGC Standards for Use in LLNL GIS

Over the summer of 2005, the Lawrence Livermore National Laboratory (LLNL) Computer Applications and Research Department conducted a small project that examined whether Open Geospatial Consortium (OGC) standards might be useful in meeting program mission requirements more effectively. OGC standards are intended to facilitate interoperability between geospatial processing systems to lower development costs and to avoid duplication of effort and vendor lock-in. Some OGC standards appear to be gaining traction in the geospatial data community, the Federal government, Department of Energy (DOE) and Department of Homeland Security (DHS) and so an evaluation was deemed appropriate

Functional Bone Engineering Using ex Vivo Gene Therapy and Topology-Optimized, Biodegradable Polymer Composite Scaffolds

Bone tissue engineering could provide an alternative to conventional treatments for fracture nonunion, spinal fusion, joint replacement, and pathological loss of bone. However, this approach will require a biocompatible matrix to allow progenitor cell delivery and support tissue invasion. The construct must also support physiological loads as it degrades to allow the regenerated tissue to bear an increasing load. To meet these complex requirements, we have employed topology-optimized design and solid free-form fabrication to manufacture biodegradable poly(propylene fumarate)/ β-tricalcium phosphate composites. These scaffolds were seeded with primary human fibroblasts transduced with an adenovirus expressing bone morphogenetic protein-7 and implanted subcutaneously in mice. Specimens were evaluated by microcomputed tomography, compressive testing, and histological staining. New bone was localized on the scaffold surface and closely followed its designed contours. Furthermore, the total stiffness of the constructs was retained for up to 12 weeks after implantation, as scaffold degradation and tissue invasion took place.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63144/1/ten.2005.11.1589.pd

Plug and Play: Interoperability in Concert

In order to make database systems interoperate with systems beyond traditional application areas a new paradigm called "exporting database functionality" as a radical departure from traditional thinking has been proposed in research anddevelopment. Traditionally, all data is loaded into and owned by the database, whereas according to the new paradigm data may reside outside the database in external repositories or archives. Nevertheless, database functionality, such as query processing, and indexing, is provided exploiting interoperability ofthe DBMS with the external repositories. Obviously, there is an overhead involved having the DBMS interoperate with external repositories instead of a priori loading all data into the DBMS. In this paper we discuss alternatives for interoperability at di erent levels of abstraction, and we report on evaluations performed using the Concert prototype system making these cost factors explicit

Kondo resonance behavior of heavy fermion f-electron materials (invited)

The Kondo properties of the impurity Anderson model provide a theoretical framework for relating thermodynamic and angle integrated electron spectroscopy data in many heavy fermion materials. We describe the success and the challenges of this approach, summarize a detailed analysis of CeSi2,CeSi2, and give a perspective on the relation to the lattice Anderson model. © 2000 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71136/2/JAPIAU-87-9-6088-1.pd

Hydrazines as versatile chemical biology probes and drug-discovery tools for cofactor-dependent enzymes [preprint]

Known chemoproteomic probes generally use warheads that tag a single type of amino acid or modified form thereof to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electron-poor enzyme cofactors, transient intermediates and chemically-labile regulatory modifications, but probes for such species are underdeveloped. Here, we have innovated a versatile class of chemoproteomic probes for this less charted hemisphere of the proteome by using hydrazine as the common chemical warhead. Its electron-rich nature allows it to react by both polar and radicaloid mechanisms and to target multiple, pharmacologically important functional classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment can be blocked by active-site-directed inhibitors, and elaboration of the warhead supports connection of a target to a lead compound. The capacity of substituted hydrazines to profile, discover and inhibit diverse cofactor-dependent enzymes enables cell and tissue imaging and makes this platform useful for enzyme and drug discovery

18S rRNA is a reliable normalisation gene for real time PCR based on influenza virus infected cells

Background: One requisite of quantitative reverse transcription PCR (qRT-PCR) is to normalise the data with an internal reference gene that is invariant regardless of treatment, such as virus infection. Several studies have found variability in the expression of commonly used housekeeping genes, such as beta-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), under different experimental settings. However, ACTB and GAPDH remain widely used in the studies of host gene response to virus infections, including influenza viruses. To date no detailed study has been described that compares the suitability of commonly used housekeeping genes in influenza virus infections. The present study evaluated several commonly used housekeeping genes [ACTB, GAPDH, 18S ribosomal RNA (18S rRNA), ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5B) and ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C1 (subunit 9) (ATP5G1)] to identify the most stably expressed gene in human, pig, chicken and duck cells infected with a range of influenza A virus subtypes. Results: The relative expression stability of commonly used housekeeping genes were determined in primary human bronchial epithelial cells (HBECs), pig tracheal epithelial cells (PTECs), and chicken and duck primary lung-derived cells infected with five influenza A virus subtypes. Analysis of qRT-PCR data from virus and mock infected cells using NormFinder and BestKeeper software programmes found that 18S rRNA was the most stable gene in HBECs, PTECs and avian lung cells. Conclusions: Based on the presented data from cell culture models (HBECs, PTECs, chicken and duck lung cells) infected with a range of influenza viruses, we found that 18S rRNA is the most stable reference gene for normalising qRT-PCR data. Expression levels of the other housekeeping genes evaluated in this study (including ACTB and GPADH) were highly affected by influenza virus infection and hence are not reliable as reference genes for RNA normalisation

Selection of suitable reference genes for accurate normalization of gene expression profile studies in non-small cell lung cancer

BACKGROUND: In real-time RT quantitative PCR (qPCR) the accuracy of normalized data is highly dependent on the reliability of the reference genes (RGs). Failure to use an appropriate control gene for normalization of qPCR data may result in biased gene expression profiles, as well as low precision, so that only gross changes in expression level are declared statistically significant or patterns of expression are erroneously characterized. Therefore, it is essential to determine whether potential RGs are appropriate for specific experimental purposes. Aim of this study was to identify and validate RGs for use in the differentiation of normal and tumor lung expression profiles. METHODS: A meta-analysis of lung cancer transcription profiles generated with the GeneChip technology was used to identify five putative RGs. Their consistency and that of seven commonly used RGs was tested by using Taqman probes on 18 paired normal-tumor lung snap-frozen specimens obtained from non-small-cell lung cancer (NSCLC) patients during primary curative resection. RESULTS: The 12 RGs displayed showed a wide range of Ct values: except for rRNA18S (mean 9.8), the mean values of all the commercial RGs and ESD ranged from 19 to 26, whereas those of the microarray-selected RGs (BTF-3, YAP1, HIST1H2BC, RPL30) exceeded 26. RG expression stability within sample populations and under the experimental conditions (tumour versus normal lung specimens) was evaluated by: (1) descriptive statistic; (2) equivalence test; (3) GeNorm applet. All these approaches indicated that the most stable RGs were POLR2A, rRNA18S, YAP1 and ESD. CONCLUSION: These data suggest that POLR2A, rRNA18S, YAP1 and ESD are the most suitable RGs for gene expression profile studies in NSCLC. Furthermore, they highlight the limitations of commercial RGs and indicate that meta-data analysis of genome-wide transcription profiling studies may identify new RGs

Naturally Embedded Query Languages

We investigate the properties of a simple programming language whose main computational engine is structural recursion on sets. We describe a progression of sublanguages in this paradigm that (1) have increasing expressive power, and (2) illustrate robust conceptual restrictions thus exhibiting interesting additional properties. These properties suggest that we consider our sublanguages as candidates for "query languages". Viewing query languages as restrictions of our more general programming language has several advantages. First, there is no "impedance mismatch" problem; the query languages are already there, so they share common semantic foundation with the general language. Second, we suggest a uniform characterization of nested relational and complex-object algebras in terms of some surprisingly simple operators; and we can make comparisons of expressiveness in a general framework. Third, we exhibit differences in expressive power that are not always based on complexity arguments..