Claremont Colleges Emergency Preparedness: An Action Research Initiative

This study examines the role of knowledge management systems in the context of emergency preparedness at Claremont University Consortium. The research objectives required the researcher's direct involvement with CUC. Canonical action research methodology was used to guide the project. Overall, the client was satisfied with the project's outcome. The researcher designed and implemented an instantiation of a web-based knowledge management system using Wiki technology. This system can assist CUC in overcoming some of its immediate concerns with emergency preparedness. These include the ability of the system to facilitate the communication process, and enable a more structured approach for documenting and storing emergency related information. The system as it exists today is subject to further improvement. This includes the need for continuous training with the system, improving the navigational aspects, and seeking a better fit between the system and the emergency planning and response processes.

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.     

下一代传输网络：传输、管理和控制位面

本书全面论述了传输、管理和控制位面的技术，介绍了一些有用的、现行的和下一代电讯网络技术的参考信息。四位作者均在电信学研究、产品开发等方面具有20年以上的经验。     

Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections

The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta.     

High-resolution structure prediction and the crystallographic phase problem

The energy-based refinement of low-resolution protein structure models to atomic-level accuracy is a major challenge for computational structural biology. Here we describe a new approach to refining protein structure models that focuses sampling in regions most likely to contain errors while allowing the whole structure to relax in a physically realistic all-atom force field. In applications to models produced using nuclear magnetic resonance data and to comparative models based on distant structural homologues, the method can significantly improve the accuracy of the structures in terms of both the backbone conformations and the placement of core side chains. Furthermore, the resulting models satisfy a particularly stringent test: they provide significantly better solutions to the X-ray crystallographic phase problem in molecular replacement trials. Finally, we show that all-atom refinement can produce de novo protein structure predictions that reach the high accuracy required for molecular replacement without any experimental phase information and in the absence of templates suitable for molecular replacement from the Protein Data Bank. These results suggest that the combination of high-resolution structure prediction with state-of-the-art phasing tools may be unexpectedly powerful in phasing crystallographic data for which molecular replacement is hindered by the absence of sufficiently accurate previous models.     

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.     

Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes

The oxylipin pathway generates not only prostaglandin-like jasmonates but also green leaf volatiles (GLVs), which confer characteristic aromas to fruits and vegetables. Although allene oxide synthase (AOS) and hydroperoxide lyase are atypical cytochrome P450 family members involved in the synthesis of jasmonates and GLVs, respectively, it is unknown how these enzymes rearrange their hydroperoxide substrates into different products. Here we present the crystal structures of Arabidopsis thaliana AOS, free and in complex with substrate or intermediate analogues. The structures reveal an unusual active site poised to control the reactivity of an epoxyallylic radical and its cation by means of interactions with an aromatic pi-system. Replacing the amino acid involved in these steps by a non-polar residue markedly reduces AOS activity and, unexpectedly, is both necessary and sufficient for converting AOS into a GLV biosynthetic enzyme. Furthermore, by combining our structural data with bioinformatic and biochemical analyses, we have discovered previously unknown hydroperoxide lyase in plant growth-promoting rhizobacteria, AOS in coral, and epoxyalcohol synthase in amphioxus. These results indicate that oxylipin biosynthetic genes were present in the last common ancestor of plants and animals, but were subsequently lost in all metazoan lineages except Placozoa, Cnidaria and Cephalochordata.     

Knowledge Management for Social Workers Involved in Disaster Planning and Response in Malaysia: An Action Research Approach

This paper explores the idea of using a knowledge management system to support disaster planning and response (DPR) efforts for social workers involved in such efforts in Malaysia. The study was funded by the Government of Malaysia. Canonical Action Research was used to conduct the study. The Malaysian Association of Social Workers (MASW) was the client organization. The study began with problem formulation to ascertain issues inherent in DPR within the MASW. The next phase of the research, involved action planning—the team considered implementing a web-based knowledge management (KM) system to support DPR efforts for the organization. Post intervention, we conducted an evaluation of our action, based on interviews with key members affiliated to the MASW. Our findings are in tandem with prior work that has examined the role and relevance of KM systems in light of DPR efforts. The client organization in general forms the view that KM systems can support DPR efforts by providing vital information (pertaining to DPR) and assist the overall coordination and planning efforts for the organization.     

Synthetic investigations in diterpenoids

Zusammenfassung Die synthese von 1,1-Dimethyl-4a-methyl-6-methyoxy-1,2,3,4,4a,9,10,10a-octahydrophenanthren (dl-6-Methoxypodocarpan) aus 1-Methyl-7-methoxytetralon-2 wird beschrieben.