The Experience of Establishing Data Sharing & Linkage Platforms for Administrative, Research and Community-Service Data

Introduction Innovative data platforms (e.g. biobanks, repositories) continually emerge to facilitate data sharing. Extant and emerging data platforms must navigate myriad tensions for successful data sharing and re-use. Two Alberta data platforms navigated such processes and factors regarding administrative, research and nonprofit data: the Child & Youth Data Laboratory (CYDL) and Secondary Analysis to Generate Evidence (SAGE). Objectives To clarify the social and policy factors that influenced CYDL and SAGE establishment and implementation, and the relationships, if any, between these factors and data type. Methods This paper involves a qualitative secondary analysis of two developmental evaluations on CYDL and SAGE establishment. Six-years post-implementation, the CYDL evaluation entailed document review; website user analysis; informant interviews (n=30); online stakeholder survey (n=260); and an environmental scan. One-year post implementation, the SAGE evaluation included 15 interviews and document review. We used thematic analysis and comparisons with the literature to identify key factors. Results Three (not mutually exclusive) categories of social and policy factors influenced the navigation towards CYDL and SAGE realization: trusting relationships; sustainability amidst readiness; and privacy within social context. For these platforms to be able to manage, link or share data, trust had to be fostered and maintained across multiple, dynamic and intersecting relationships between primary data producers, data subjects, secondary users and institutions. Platform sustainability and readiness required capacity building and innovation. Privacy and information sharing evolved culturally and correspondingly for these data platforms, which required constant flexibility and awareness. Conclusions This commentary calls for more empirical research on the value of data re-use or the detriment in not re-using data. While the culture of information sharing is progressing towards greater openness and capacity for data sharing and re-use, successful data platforms must advocate, facilitate and mobilize analysis and innovation using data re-use while being cognizant of social and policy influences

Complementary analysis of Mueller-matrix images of optically anisotropic highly scattering biological tissues

Background: Using optical techniques for tissue diagnostics (so-called ‘optical biopsy’) has been a subject of extensive research for many years. Various groups have been exploring different spectral and/or imaging modalities (e.g. diffuse reflectance spectroscopy, autofluorescence, Raman spectroscopy, optical coherence tomography (OCT), polarized light microscopy, etc.) for biomedical applications. In this paper, we report on using multi-wavelength imaging Mueller polarimetry combined with an appropriated image post-processing for the detection of tissue malignancy. Methods: We investigate a possibility of complementary analysis of Mueller matrix images obtained for turbid tissue-like scattering phantoms and excised human normal and cancerous colorectal tissue samples embedded in paraffin. Combined application of correlation, fractal and statistical analysis was employed to assess quantitatively the polarization-inhomogeneous scattered fields observed at the surface of tissue samples. Results: The combined analysis of the polarimetric images of paraffin-embedded tissue blocks has proved to be an efficient tool for the unambiguous detection of tissue malignant transformation. A fractal structure was clearly observed at spatial distributions of depolarization of light scattered in healthy tissues in a visible range of spectrum, while corresponding distributions for cancerous tissues did not show such dependence. We demonstrate that paraffin does not destroy a fractal structure of spatial distribution of depolarization. Thus, the loss of fractality in spatial distributions of depolarization for cancerous tissue is related to the structural changes in the tissue sample induced by cancer itself and, therefore, may serve as a marker of the disease. Conclusion: The obtained results emphasize that a combined use of statistical, correlation and fractal analysis for the Mueller-matrix image post-processing is an effective approach for an assessment of variations of optical properties in turbid tissue-like scattering media and biological tissues, with a high potential to be transferred to clinical practice for screening cancerous tissue samples

Identifying divergent design thinking through the observable behavior of service design novices

© 2018, Springer Nature B.V. Design thinking holds the key to innovation processes, but is often difficult to detect because of its implicit nature. We undertook a study of novice designers engaged in team-based design exercises in order to explore the correlation between design thinking and designers’ physical (observable) behavior and to identify new, objective, design thinking identification methods. Our study addresses the topic by using data collection method of “think aloud” and data analysis method of “protocol analysis” along with the unconstrained concept generation environment. Collected data from the participants without service design experience were analyzed by open and selective coding. Through the research, we found correlations between physical activity and divergent thinking, and also identified physical behaviors that predict a designer’s transition to divergent thinking. We conclude that there are significant relations between designers’ design thinking and the behavioral features of their body and face. This approach opens possible new ways to undertake design process research and also design capability evaluation

Transcriptomic profiling of host-parasite interactions in the microsporidian <i>Trachipleistophora hominis</i>

BACKGROUND: Trachipleistophora hominis was isolated from an HIV/AIDS patient and is a member of a highly successful group of obligate intracellular parasites. METHODS: Here we have investigated the evolution of the parasite and the interplay between host and parasite gene expression using transcriptomics of T. hominis-infected rabbit kidney cells. RESULTS: T. hominis has about 30 % more genes than small-genome microsporidians. Highly expressed genes include those involved in growth, replication, defence against oxidative stress, and a large fraction of uncharacterised genes. Chaperones are also highly expressed and may buffer the deleterious effects of the large number of non-synonymous mutations observed in essential T. hominis genes. Host expression suggests a general cellular shutdown upon infection, but ATP, amino sugar and nucleotide sugar production appear enhanced, potentially providing the parasite with substrates it cannot make itself. Expression divergence of duplicated genes, including transporters used to acquire host metabolites, demonstrates ongoing functional diversification during microsporidian evolution. We identified overlapping transcription at more than 100 loci in the sparse T. hominis genome, demonstrating that this feature is not caused by genome compaction. The detection of additional transposons of insect origin strongly suggests that the natural host for T. hominis is an insect. CONCLUSIONS: Our results reveal that the evolution of contemporary microsporidian genomes is highly dynamic and innovative. Moreover, highly expressed T. hominis genes of unknown function include a cohort that are shared among all microsporidians, indicating that some strongly conserved features of the biology of these enormously successful parasites remain uncharacterised. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1989-z) contains supplementary material, which is available to authorized users

Functional kinomics establishes a critical node of volume-sensitive cation-Cl^- cotransporter regulation in the mammalian brain

This is the final version of the article. Available from the publisher via the DOI in this record.There is another record in ORE for this publication: http://hdl.handle.net/10871/33424Cell volume homeostasis requires the dynamically regulated transport of ions across the plasmalemma. While the ensemble of ion transport proteins involved in cell volume regulation is well established, the molecular coordinators of their activities remain poorly characterized. We utilized a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-content kinase inhibitor screen, and a kinase trapping-Orbitrap mass spectroscopy screen to systematically identify essential kinase regulators of KCC3 Thr991/Thr1048 phosphorylation – a key signaling event in cell swelling-induced regulatory volume decrease (RVD). In the mammalian brain, we found the Cl−-sensitive WNK3-SPAK kinase complex, required for cell shrinkage-induced regulatory volume decrease (RVI) via the stimulatory phosphorylation of NKCC1 (Thr203/Thr207/Thr212), is also essential for the inhibitory phosphorylation of KCC3 (Thr991/Thr1048). This is mediated in vivo by an interaction between the CCT domain in SPAK and RFXV/I domains in WNK3 and NKCC1/KCC3. Accordingly, genetic or pharmacologic WNK3-SPAK inhibition prevents cell swelling in response to osmotic stress and ameliorates post-ischemic brain swelling through a simultaneous inhibition of NKCC1-mediated Cl− uptake and stimulation of KCC3-mediated Cl− extrusion. We conclude that WNK3-SPAK is an integral component of the long-sought “Cl−/volume-sensitive kinase” of the cation-Cl− cotransporters, and functions as a molecular rheostat of cell volume in the mammalian brain.We thank the excellent technical support of the MRC-Protein Phosphorylation and Ubiquitylation Unit (PPU) DNA Sequencing Service (coordinated by Nicholas Helps), the MRC-PPU tissue culture team (coordinated by Laura Fin), the Division of Signal Transduction Therapy (DSTT) antibody purification teams (coordinated by Hilary McLauchlan and James Hastie). We are grateful to the MRC PPU Proteomics facility (coordinated by David Campbell, Robert Gourlay and Joby Varghese). We thank for support the Medical Research Council (MC_UU_12016/2; DRA) and the pharmaceutical companies supporting the Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica and Pfizer; DRA). We thank Thomas J. Jentsch (Max-Delbrück-Centrum für Molekulare Medizin) for providing the KCC1/3 double KO mice and his reading of this manuscript. We thank Nathaniel Grey (Harvard) for providing the kinase inhibitor library used in this study (NIH LINCS Program grant U54HL127365). This work was also supported by a Harvard-MIT Neuroscience Grant (to KTK/SJE)

Leishmania infantum Asparagine Synthetase A Is Dispensable for Parasites Survival and Infectivity

A growing interest in asparagine (Asn) metabolism has currently been observed in cancer and infection fields. Asparagine synthetase (AS) is responsible for the conversion of aspartate into Asn in an ATP-dependent manner, using ammonia or glutamine as a nitrogen source. There are two structurally distinct AS: the strictly ammonia dependent, type A, and the type B, which preferably uses glutamine. Absent in humans and present in trypanosomatids, AS-A was worthy of exploring as a potential drug target candidate. Appealingly, it was reported that AS-A was essential in Leishmania donovani, making it a promising drug target. In the work herein we demonstrate that Leishmania infantum AS-A, similarly to Trypanosoma spp. and L. donovani, is able to use both ammonia and glutamine as nitrogen donors. Moreover, we have successfully generated LiASA null mutants by targeted gene replacement in L. infantum, and these parasites do not display any significant growth or infectivity defect. Indeed, a severe impairment of in vitro growth was only observed when null mutants were cultured in asparagine limiting conditions. Altogether our results demonstrate that despite being important under asparagine limitation, LiAS-A is not essential for parasite survival, growth or infectivity in normal in vitro and in vivo conditions. Therefore we exclude AS-A as a suitable drug target against L. infantum parasites

In search of the representative pharmacophore hypotheses of the enzymatic proteome of Plasmodium falciparum: a multicomplex-based approach

Drug resistance has made malaria an untreatable disease and therefore intensified the need for the development of new drugs and the identification of potential drug targets. In this pursuit, in silico efforts made in the past have not shown significant responses. Therefore, in the present work, the multicomplex-based pharmacophore modeling approach was employed to construct the pharmacophores of the 16 selected Plasmodium falciparum (Pf) targets. All the constructed hypotheses (153) were screened against a focused dataset made up of experimental actives of the chosen targets (3705 inhibitors). The rationale was to check the affinity of the inhibitors for the off-targets. Subsequently, the constructed hypotheses from each target were pooled based on the feature types and the pooled-hypotheses were then clustered to offer an insight about the pharmacophore similarity. Tanimoto similarity index was also calculated to look for the similarity among the inhibitors belonging to different Pf targets. Overall, the work was accomplished to bid healthier perceptive of the pharmacophore-based virtual screening and abet in providing guiding principles for the construction of stringent pharmacophores that can be employed for the screening.by Anu Manhas, Mohsin Y. Lone and Prakash C. Jh

Synthesis and characterization of iron(IV), cobalt(IV), nickel(III) and copper(III) complexes of 4-methylpiperazine-1-carbodithioate

160-163A few complexes of the type [M(4-Mpipzcdt)n]CIO4 (where n=3 for M=FeIV, COIV; n=2 for M=NiIIICuIII; 4-MPipzcdt = 4-methylpiperazine-1-carbodithioato) have been isolated by the oxidation of M( 4-MPipzcdt)n, (n = 3 for M = FeIII, COllI and n = 2 for M = NII and CUll) with Fe(CIO4)3.9H2O. These complexes have been characterised by elemental analyses, room-temperature infrared and electronic spectral and magnetic susceptibility measurements