“NoSQL” And Service Science

Discussions of “NoSQL” naturally tend to contrast a new approach with a tired old approach. An example is the discussion in Linux Journal (Batholomew, 2010) which focused on differentiating between these new “nonrelational” products and “traditional” (relational) systems. While enthusiasm for the new (and the unjustified raised expectations) has often been the hallmark of information systems and computing, in this instance the enthusiasm may be providing a poor and misleading explanation. A more careful explanation is needed, particularly as these approaches and products may be needed to provide the realization of many promising ideas such as those associated as with Web Services

Green fluorescent protein-based assays for high-throughput functional characterization and ligand-binding studies of biotin protein ligase

In E. coli and other prokaryotes such as Staphylococcus aureus, and Mycobacterium tuberculosis, biotin protein ligase (BirA) is an emerging drug target as it is the sole enzyme capable of biotin transfer onto the BCCP subunit of ACC. There is currently a gap in simple yet efficient assays for rapidly identifying and characterising inhibitors targeting BirA. We present for the first time the development and validation of a simple and reliable DSF-GTP assay for the high-throughput screening of BirA: ligand interactions using a new GFP-tagged BirA of E. coli. In addition, we developed a new GFP-based biotinylation activity assay taking advantage of a GFP tethered with an AviTag. The data obtained with these assays revealed new insights into how the binding of individual or combinations of ligands affect the overall thermal stability and affinity of BirA. The DSF-GTP assay has a Z' value of 0.785 that makes it an excellent tool for future high-throughput screening of inhibitory compounds

Selective protein unfolding: a universal mechanism of action for the development of irreversible inhibitors

High-throughput differential scanning fluorimetry of GFP-tagged proteins (HT-DSF-GTP) was applied for the identification of novel enzyme inhibitors acting by a mechanism termed: selective protein unfolding (SPU). Four different protein targets were interrogated with the same library to identify target-selective hits. Several hits selectively destabilized bacterial biotin protein ligase. Structure–activity relationship data confirmed a structure-dependent mechanism of protein unfolding. Simvastatin and altenusin were confirmed to irreversibly inactivate biotin protein ligase. The principle of SPU combined with HT-DSF-GTP affords an invaluable and innovative workflow for the identification of new inhibitors with potential applications as antimicrobials and other biocides

Statistical properties of the Burgers equation with Brownian initial velocity

We study the one-dimensional Burgers equation in the inviscid limit for Brownian initial velocity (i.e. the initial velocity is a two-sided Brownian motion that starts from the origin x=0). We obtain the one-point distribution of the velocity field in closed analytical form. In the limit where we are far from the origin, we also obtain the two-point and higher-order distributions. We show how they factorize and recover the statistical invariance through translations for the distributions of velocity increments and Lagrangian increments. We also derive the velocity structure functions and we recover the bifractality of the inverse Lagrangian map. Then, for the case where the initial density is uniform, we obtain the distribution of the density field and its $n$-point correlations. In the same limit, we derive the $n-$point distributions of the Lagrangian displacement field and the properties of shocks. We note that both the stable-clustering ansatz and the Press-Schechter mass function, that are widely used in the cosmological context, happen to be exact for this one-dimensional version of the adhesion model.Comment: 42 pages, published in J. Stat. Phy

Developing a tool to measure health worker motivation in district hospitals in Kenya

BACKGROUND: We wanted to try to account for worker motivation as a key factor that might affect the success of an intervention to improve implementation of health worker practices in eight district hospitals in Kenya. In the absence of available tools, we therefore aimed to develop a tool that could enable a rapid measurement of motivation at baseline and at subsequent points during the 18-month intervention study. METHODS: After a literature review, a self-administered questionnaire was developed to assess the outcomes and determinants of motivation of Kenyan government hospital staff. The initial questionnaire included 23 questions (from seven underlying constructs) related to motivational outcomes that were then used to construct a simpler tool to measure motivation. Parallel qualitative work was undertaken to assess the relevance of the questions chosen and the face validity of the tool. RESULTS: Six hundred eighty-four health workers completed the questionnaires at baseline. Reliability analysis and factor analysis were used to produce the simplified motivational index, which consisted of 10 equally-weighted items from three underlying factors. Scores on the 10-item index were closely correlated with scores for the 23-item index, indicating that in future rapid assessments might be based on the 10 questions alone. The 10-item motivation index was also able to identify statistically significant differences in mean health worker motivation scores between the study hospitals (p<0.001). The parallel qualitative work in general supported these conclusions and contributed to our understanding of the three identified components of motivation. CONCLUSION: The 10-item score developed may be useful to monitor changes in motivation over time within our study or be used for more extensive rapid assessments of health worker motivation in Kenya

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity

Quality of the parent-child interaction in young children with type 1 diabetes mellitus: study protocol

<p>Abstract</p> <p>Background</p> <p>In young children with type 1 diabetes mellitus (T1DM) parents have full responsibility for the diabetes-management of their child (e.g. blood glucose monitoring, and administering insulin). Behavioral tasks in childhood, such as developing autonomy, and oppositional behavior (e.g. refusing food) may interfere with the diabetes-management to achieve an optimal blood glucose control. Furthermore, higher blood glucose levels are related to more behavioral problems. So parents might need to negotiate with their child on the diabetes-management to avoid this direct negative effect. This interference, the negotiations, and the parent's responsibility for diabetes may negatively affect the quality of parent-child interaction. Nevertheless, there is little knowledge about the quality of interaction between parents and young children with T1DM, and the possible impact this may have on glycemic control and psychosocial functioning of the child. While widely used global parent-child interaction observational methods are available, there is a need for an observational tool specifically tailored to the interaction patterns of parents and children with T1DM. The main aim of this study is to construct a disease-specific observational method to assess diabetes-specific parent-child interaction. Additional aim is to explore whether the quality of parent-child interactions is associated with the glycemic control, and psychosocial functioning (resilience, behavioral problems, and quality of life).</p> <p>Methods/Design</p> <p>First, we will examine which situations are most suitable for observing diabetes-specific interactions. Then, these situations will be video-taped in a pilot study (N = 15). Observed behaviors are described into rating scales, with each scale describing characteristics of parent-child interactional behaviors. Next, we apply the observational tool on a larger scale for further evaluation of the instrument (N = 120). The parents are asked twice (with two years in between) to fill out questionnaires about psychosocial functioning of their child with T1DM. Furthermore, glycemic control (HbA_1c) will be obtained from their medical records.</p> <p>Discussion</p> <p>A disease-specific observational tool will enable the detailed assessment of the quality of diabetes-specific parent-child interactions. The availability of such a tool will facilitate future (intervention) studies that will yield more knowledge about impact of parent-child interactions on psychosocial functioning, and glycemic control of children with T1DM.</p

The Physical and Genetic Framework of the Maize B73 Genome

Maize is a major cereal crop and an important model system for basic biological research. Knowledge gained from maize research can also be used to genetically improve its grass relatives such as sorghum, wheat, and rice. The primary objective of the Maize Genome Sequencing Consortium (MGSC) was to generate a reference genome sequence that was integrated with both the physical and genetic maps. Using a previously published integrated genetic and physical map, combined with in-coming maize genomic sequence, new sequence-based genetic markers, and an optical map, we dynamically picked a minimum tiling path (MTP) of 16,910 bacterial artificial chromosome (BAC) and fosmid clones that were used by the MGSC to sequence the maize genome. The final MTP resulted in a significantly improved physical map that reduced the number of contigs from 721 to 435, incorporated a total of 8,315 mapped markers, and ordered and oriented the majority of FPC contigs. The new integrated physical and genetic map covered 2,120 Mb (93%) of the 2,300-Mb genome, of which 405 contigs were anchored to the genetic map, totaling 2,103.4 Mb (99.2% of the 2,120 Mb physical map). More importantly, 336 contigs, comprising 94.0% of the physical map (∼1,993 Mb), were ordered and oriented. Finally we used all available physical, sequence, genetic, and optical data to generate a golden path (AGP) of chromosome-based pseudomolecules, herein referred to as the B73 Reference Genome Sequence version 1 (B73 RefGen_v1)

A Daphnane Diterpenoid Isolated from Wikstroemia polyantha Induces an Inflammatory Response and Modulates miRNA Activity

MicroRNAs (miRNAs) are endogenously expressed single-stranded ∼21–23 nucleotide RNAs that inhibit gene expression post-transcriptionally by binding imperfectly to elements usually within the 3′untranslated region (3′UTR) of mRNAs. Small interfering RNAs (siRNAs) mediate site-specific cleavage by binding with perfect complementarity to RNA. Here, a cell-based miRNA reporter system was developed to screen for compounds from marine and plant extracts that inhibit miRNA or siRNA activity. The daphnane diterpenoid genkwanine M (GENK) isolated from the plant Wikstroemia polyantha induces an early inflammatory response and can moderately inhibit miR-122 activity in the liver Huh-7 cell line. GENK does not alter miR-122 levels nor does it directly inhibit siRNA activity in an in vitro cleavage assay. Finally, we demonstrate that GENK can inhibit HCV infection in Huh-7 cells. In summary, the development of the cell-based miRNA sensor system should prove useful in identifying compounds that affect miRNA/siRNA activity