Effective Knowledge Management (KM) strategy within a business organization

A cohesive Knowledge Management (KM) strategy is found at the cornerstone of every successful business enterprise\u27s overall business strategy. The full benefit of this strategy can only be achieved through a dynamic, technology-enabled framework that encourages best and better practices to capture the outputs of human innovation and creative knowledge. Competitive pressures and technological convergence, most prevalent in high technology business sectors, have demonstrated the critical need for an information strategy that can harness and discern the continual amass of intellectual property. The continual accumulation of information and knowledge critical to the sustained viability of many business organizations, presents significant and complex management challenges. The dynamic changes in economic conditions and technical innovation and advance, coupled with the need to manage the outputs of human innovation and creative capacity, continues to present a paradigm shift from the traditional management approaches to more adaptive, dynamic, non-traditional management approaches and technology solutions. A major KM challenge many organizations continue to face is no longer just how to capture and manage their intellectual property, but how to identify and discern between true intellectual content and simple information, the real knowledge of their business. A successful KM strategy becomes synonymous with the overall business strategy, and includes the requirement for a process model that provides a framework that can be adapted to an ever-changing business model. This framework must provide the ability to identify and discern between static data or information and dynamic intellectual property, which the latter is often the direct output of human creativity and innovation.1 Accordingly, one important aspect of KM as a practice is the development of knowledge transfer systems. However, the one-size-fits-all approach to the technical solution is only part of the success equation.2 The other critical element in the equation is the approach to integrate it into the related business process framework. The means of specific process improvement may vary based on business requirements and scope of technical solution, but the underlying basis of need for change or improvement remains a constant. A foundational framework for business process strategy and execution takes on much greater significance as part of the overall business strategy. Thomas A. Stewart, a member of the board of editors at Fortune Magazine, says Because knowledge has become the single most important factor of production, managing intellectual assets has become the single most important task of business. This paper will focus on the discipline of knowledge management and associated knowledge transfer practices in a pragmatic context to illustrate its importance as an integral component of a successful business strategy. This includes the perspectives of both as strategic asset in the management of intellectual capital, and as an enabling technology to leverage the intellectual capital for business fulfillment. The assertions and discussions put forth, while centered on knowledge management, can be paralleled for several IT-centric business disciplines. However, the analysis of the research and case studies referenced in this paper will illustrate the growing breadth and importance of knowledge assets as the primary cornerstone in a broad spectrum of business disciplines. More importantly, it will clearly demonstrate the critical need to effectively manage and control knowledge assets for competitive advantage as part of the overall business strategy. 1 Yogesh Malhotra, Knowledge Management for E-business Performance: Advancing Information Strategy to Internet Time ; Information Strategy, The Executive\u27s Journal. Summer 2000, vol. 16 (4), pp. 5-16 2 James Conlan, Improving Business Processes , KMWorld, November/December 2001, pp. S13

Communicating the Threat of a Tropical Cyclone to the Eastern Range

The 45th Weather Squadron (45 WS) has developed a tool to help visualize the Wind Speed Probability product from the National Hurricane Center (NHC) and to help communicate that information to space launch customers and decision makers at the 45th Space Wing (45 SW) and Kennedy Space Center (KSC) located in east central Florida. This paper reviews previous work and presents the new visualization tool, including initial feedback as well as the pros and cons. The NHC began issuing their Wind Speed Probability product for tropical cyclones publicly in 2006. The 45 WS uses this product to provide a threat assessment to 45 SW and KSC leadership for risk evaluations with an approaching tropical cyclone. Although the wind speed probabilities convey the uncertainty of a tropical cyclone well, communicating this information to customers is a challenge. The 45 WS continually strives to provide the wind speed probability information to customers in a context which clearly communicates the threat of a tropical cyclone. First, an intern from the Florida Institute of Technology (FIT) Atmospheric Sciences department, sponsored by Scitor Corporation, independently evaluated the NHC wind speed probability product. This work was later extended into a M.S. thesis at FIT, partially funded by Scitor Corporation and KSC. A second thesis at FIT further extended the evaluation partially funded by KSC. Using this analysis, the 45 WS categorized the probabilities into five probability interpretation categories: Very Low, Low, Moderate, High, and Very High. These probability interpretation categories convert the forecast probability and forecast interval into easily understood categories that are consistent across all ranges of probabilities and forecast intervals. As a follow-on project, KSC funded a summer intern to evaluate the human factors of the probability interpretation categories, which ultimately refined some of the thresholds. The 45 WS created a visualization tool to express the timing and risk for multiple locations in a single graphic. Preliminary results on an on-going project by FIT will be included in this paper. This project is developing a new method of assigning the probability interpretation categories and updating the evaluation of the performance of the NHC wind speed probability analysis

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Coactivator condensation at super-enhancers links phase separation and gene control

Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes

Multiple Recurrent De Novo CNVs, Including Duplications of the 7q11.23 Williams Syndrome Region, Are Strongly Associated with Autism

SummaryWe have undertaken a genome-wide analysis of rare copy-number variation (CNV) in 1124 autism spectrum disorder (ASD) families, each comprised of a single proband, unaffected parents, and, in most kindreds, an unaffected sibling. We find significant association of ASD with de novo duplications of 7q11.23, where the reciprocal deletion causes Williams-Beuren syndrome, characterized by a highly social personality. We identify rare recurrent de novo CNVs at five additional regions, including 16p13.2 (encompassing genes USP7 and C16orf72) and Cadherin 13, and implement a rigorous approach to evaluating the statistical significance of these observations. Overall, large de novo CNVs, particularly those encompassing multiple genes, confer substantial risks (OR = 5.6; CI = 2.6–12.0, p = 2.4 × 10-7). We estimate there are 130–234 ASD-related CNV regions in the human genome and present compelling evidence, based on cumulative data, for association of rare de novo events at 7q11.23, 15q11.2-13.1, 16p11.2, and Neurexin 1

Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level

Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014