In-house Projects Research Articles

Do knowledge translation (KT) plans help to structure KT practices?

BackgroundA knowledge translation (KT) planning template is a roadmap laying out the core elements to be considered when structuring the implementation of KT activities by researchers and practitioners. Since 2010, the Institut national de santé publique du Québec (INSPQ; Québec Public Health Institute) has provided tools and guidance to in-house project teams to help them develop KT plans. This study sought to identify the dimensions included in those plans and which ones were integrated and how. The results will be of interest to funding agencies and scientific organizations that provide frameworks for KT planning.MethodsThe operationalization of KT planning dimensions was assessed in a mixed methods case study of 14 projects developed at the INSPQ between 2010 and 2013. All plans were assessed (rated) using an analytical tool developed for this study and data from interviews with the planning coordinators. The analytical tool and interview guide were based on eight core KT dimensions identified in the literature.ResultsAnalysis of the plans and interviews revealed that the dimensions best integrated into the KT plans were ‘analysis of the context (barriers and facilitators) and of users’ needs’, ‘knowledge to be translated’, ‘KT partners’, ‘KT strategies’ and, to a lesser extent, ‘overall KT approach’. The least well integrated dimensions were ‘knowledge about knowledge users’, ‘KT process evaluation’ and ‘resources’.ConclusionsWhile the planning coordinators asserted that a plan did not need to include all the dimensions to ensure its quality and success, nevertheless the dimensions that received less attention might have been better incorporated if they had been supported with more instruments related to those dimensions and sustained methodological guidance. Overall, KT planning templates appear to be an appreciated mechanism for supporting KT reflexive practices. Based on this study and our experience, we recommend using KT plans cautiously when assessing project efficacy and funding.

CSAR 2014: A Benchmark Exercise Using Unpublished Data from Pharma.

The 2014 CSAR Benchmark Exercise was the last community-wide exercise that was conducted by the group at the University of Michigan, Ann Arbor. For this event, GlaxoSmithKline (GSK) donated unpublished crystal structures and affinity data from in-house projects. Three targets were used: tRNA (m1G37) methyltransferase (TrmD), Spleen Tyrosine Kinase (SYK), and Factor Xa (FXa). A particularly strong feature of the GSK data is its large size, which lends greater statistical significance to comparisons between different methods. In Phase 1 of the CSAR 2014 Exercise, participants were given several protein-ligand complexes and asked to identify the one near-native pose from among 200 decoys provided by CSAR. Though decoys were requested by the community, we found that they complicated our analysis. We could not discern whether poor predictions were failures of the chosen method or an incompatibility between the participant's method and the setup protocol we used. This problem is inherent to decoys, and we strongly advise against their use. In Phase 2, participants had to dock and rank/score a set of small molecules given only the SMILES strings of the ligands and a protein structure with a different ligand bound. Overall, docking was a success for most participants, much better in Phase 2 than in Phase 1. However, scoring was a greater challenge. No particular approach to docking and scoring had an edge, and successful methods included empirical, knowledge-based, machine-learning, shape-fitting, and even those with solvation and entropy terms. Several groups were successful in ranking TrmD and/or SYK, but ranking FXa ligands was intractable for all participants. Methods that were able to dock well across all submitted systems include MDock,1 Glide-XP,2 PLANTS,3 Wilma,4 Gold,5 SMINA,6 Glide-XP2/PELE,7 FlexX,8 and MedusaDock.9 In fact, the submission based on Glide-XP2/PELE7 cross-docked all ligands to many crystal structures, and it was particularly impressive to see success across an ensemble of protein structures for multiple targets. For scoring/ranking, submissions that showed statistically significant achievement include MDock1 using ITScore1,10 with a flexible-ligand term,11 SMINA6 using Autodock-Vina,12,13 FlexX8 using HYDE,14 and Glide-XP2 using XP DockScore2 with and without ROCS15 shape similarity.16 Of course, these results are for only three protein targets, and many more systems need to be investigated to truly identify which approaches are more successful than others. Furthermore, our exercise is not a competition.

In-house coordination project for organ and tissue procurement: social responsibility and promising results.

Objectives: to report the results of evaluation regarding changes in the number of potential donor referrals, actual donors, and conversion rates after the implementation of an in-house organ and tissue donation for transplantation coordination project. Methods: epidemiological study, both retrospective and transversal, was performed with organ donation data from the Secretariat of Health for the State and the in-house organ donation coordination project of a beneficent hospital. The data was compared using nonparametric statistical Mann-Whitney test, and the Student's t-test, considering a significance level of 5% (p <0.05). Results: there were statistically significant differences (p < 0.05), before and after the implementation of the project on the number of potential donor notification/month (3.05 - 4.7 ), number of actual donor/month (0.78 to 1.60) and rate of conversion ( 24.7 to 34.8 %). The hospitals 1, 2, 7 and 8 had significant results in potential donor, actual donor or conversion rate. Conclusion: the presence of an in-house coordinator is promising and beneficial, the specialist is important to change the indicators of efficiency, which consequently reduces the waiting lists for organ transplants.

An effective analytic method for detecting tissue-specific genes in RNA-seq experiments.

To develop an analytic method for identifying tissue-specific (TS) genes from RNA-seq data. Based on a negative binomial distribution, we develop a statistical method containing consecutive procedures incorporating data variability from replicates in each tissue. Simulations show that our approach can effectively identify at least 94% of the truly TS genes if the sample size is 3 and at least 84% of the TS genes detected by our method are truly TS genes. We illustrated the utility of our method in an in-house RNA-seq project and produced sensible results. Our approach not only directly works on discrete data but also naturally incorporates data variability. It works effectively for detecting TS genes.

On the accuracy of unit-cell parameters in protein crystallography.

The availability in the Protein Data Bank (PDB) of a number of structures that are presented in space group P1 but in reality possess higher symmetry allowed the accuracy and precision of the unit-cell parameters of the crystals of macromolecules to be evaluated. In addition, diffraction images from crystals of several proteins, previously collected as part of in-house projects, were processed independently with three popular software packages. An analysis of the results, augmented by published serial crystallography data, suggests that the apparent precision of the presentation of unit-cell parameters in the PDB to three decimal points is not justified, since these parameters are subject to errors of not less than 0.2%. It was also noticed that processing data including full crystallographic symmetry does not lead to deterioration of the refinement parameters; thus, it is not beneficial to treat the crystals as belonging to space group P1 when higher symmetry can be seen.

The Brainomics/Localizer database

The Brainomics/Localizer database exposes part of the data collected by the in-house Localizer project, which planned to acquire four types of data from volunteer research subjects: anatomical MRI scans, functional MRI data, behavioral and demographic data, and DNA sampling. Over the years, this local project has been collecting such data from hundreds of subjects. We had selected 94 of these subjects for their complete datasets, including all four types of data, as the basis for a prior publication; the Brainomics/Localizer database publishes the data associated with these 94 subjects. Since regulatory rules prevent us from making genetic data available for download, the database serves only anatomical MRI scans, functional MRI data, behavioral and demographic data.To publish this set of heterogeneous data, we use dedicated software based on the open-source CubicWeb semantic web framework. Through genericity in the data model and flexibility in the display of data (web pages, CSV, JSON, XML), CubicWeb helps us expose these complex datasets in original and efficient ways.

CRISPRz: a database of zebrafish validated sgRNAs.

CRISPRz (http://research.nhgri.nih.gov/CRISPRz/) is a database of CRISPR/Cas9 target sequences that have been experimentally validated in zebrafish. Programmable RNA-guided CRISPR/Cas9 has recently emerged as a simple and efficient genome editing method in various cell types and organisms, including zebrafish. Because the technique is so easy and efficient in zebrafish, the most valuable asset is no longer a mutated fish (which has distribution challenges), but rather a CRISPR/Cas9 target sequence to the gene confirmed to have high mutagenic efficiency. With a highly active CRISPR target, a mutant fish can be quickly replicated in any genetic background anywhere in the world. However, sgRNA's vary widely in their activity and models for predicting target activity are imperfect. Thus, it is very useful to collect in one place validated CRISPR target sequences with their relative mutagenic activities. A researcher could then select a target of interest in the database with an expected activity. Here, we report the development of CRISPRz, a database of validated zebrafish CRISPR target sites collected from published sources, as well as from our own in-house large-scale mutagenesis project. CRISPRz can be searched using multiple inputs such as ZFIN IDs, accession number, UniGene ID, or gene symbols from zebrafish, human and mouse.

Behavioural Aspects of Software Project Management- In- House Software Development

The study was aimed at looking into the behavioural aspects of software project management in in-house software development centres in India. It was considered to investigate the relationship between sector type and major organisational factor as perceived by the in-house software project head and the collective behavioural perception of in-house software project heads on human resource management, project management practices and supportive skills and environment where in-house development happens. The study was based on survey explorative design by using a structured questionnaire which was pre-tested with 35 in-house software project heads. After making necessary modifications from the collected feedback, questionnaires were sent to nearly 300 in-house software project heads in four different sectors and finally 200 responded. The collected data was analysed using chi-square analysis, correlation and other statistical tools to draw conclusions. The study revealed the collective perception of the in-house software project heads, in the descending order of their perceived interests, towards the factors of human resource management, project management practices, and supportive skills & environment. It was also found out that there is a relationship between sector type and organisational factor as perceived by the in-house software project head. In-house development centre heads need to be concerned with the behavioural aspects of developer community in their organisation, and beginning to consider these variables in their management practices will surely help to turn out successful projects both quantitatively and qualitatively. It is time to prove through further research and experiments that the behavioural aspects of software project management in the inhouse development centres in India still need to catch up with the practices to match the global standards as set by major software development companies both in India and abroad.

Transforming a glass negative collection into a digital asset through collaborative effort

The Hughes Company Glass Negatives Collection is one of the many notable image collections held by Special Collections at the Albin O. Kuhn Library &amp; Gallery of the University of Maryland, Baltimore County. In an effort to provide public access to this set of large-format glass negatives, Special Collections and the Bibliographic and Metadata Services units worked in collaboration on an in-house project to digitise, describe and serve the images and metadata to the public via a digital content management system. The project utilised existing staff with some additional hiring of student workers and required three years to complete. This paper describes the collection, the digitisation process and the creation of the metadata records representing the images.

Visual Management in Mid-sized Construction Design Projects

Visual Management has emerged during the past decades within manufacturing and service organizations, as a system that through visualization enables the employees to better understand their role and contribution in relation to both their own organizational values and costumer needs. Visual management is not well known within the construction industry; however, the importance of visualization is well recognized. In construction design, two types of visual means are frequently applied, i.e., 3D models and visual planning. These visual means support communication and mutual understanding during design, but do however not address the management of the project. The aim of this article is to explore how visual means support the design in terms of coordination and how they utilize the potential that exists in a multi-disciplinary design team. For exploring how visual means support the design coordination, we conducted and compared two case studies qualitatively in a construction design setting. Both case studies were followed throughout the entire design process, where the design teams were semi-collocated. More than 15 semi-structured interviews were recorded and transcribed. Both cases were residential in-house projects. Based on our findings we contribute with the following: (1) by using multiple visual means, i.e., visual management, the design teams become more self-going. (2) However, the self-going supported by visual management is primarily related to a collocated setting and active engagement of all actors involved.

Microseed matrix screening for optimization in protein crystallization: what have we learned?

Protein crystals obtained in initial screens typically require optimization before they are of X-ray diffraction quality. Seeding is one such optimization method. In classical seeding experiments, the seed crystals are put into new, albeit similar, conditions. The past decade has seen the emergence of an alternative seeding strategy: microseed matrix screening (MMS). In this strategy, the seed crystals are transferred into conditions unrelated to the seed source. Examples of MMS applications from in-house projects and the literature include the generation of multiple crystal forms and different space groups, better diffracting crystals and crystallization of previously uncrystallizable targets. MMS can be implemented robotically, making it a viable option for drug-discovery programs. In conclusion, MMS is a simple, time- and cost-efficient optimization method that is applicable to many recalcitrant crystallization problems.

In-House Coordination for Organ Donation—Single-Center Experience in a Pilot Project in Germany (2006 to 2013)

A challenge for solid organ transplantation in Germany is the shortage of organs. In an effort to increase donation rates, some federal states mandated hospitals to install transplantation officers to coordinate, evaluate, and enhance the donation and transplantation processes. In 2009 the German Foundation for Organ Transplantation (DSO) implemented the In-House Coordination Project, which includes retrospective, quarterly, information technology-based case analyses of all deceased patients with primary or secondary brain injury in regard to the organ donation process in maximum care hospitals. From 2006 to 2008 an analysis of potential organ donors was performed in our hospital using a time-consuming, complex method using questionnaires, hand-written patient files, and the hospital IT documentation system (standard method). Analyses in the In-House Coordination Project are instead carried out by a proprietary semiautomated IT tool called Transplant Check, which uses easily accessible standard data records of the hospital controlling and accounting unit. The aim of our study was to compare the results of the standard method and Transplant Check in detecting and evaluating potential donors. To do so, the same period of time (2006 to 2008) was re-evaluated using the IT tool. Transplant Check was able to record significantly more patients who fulfilled the criteria for inclusion than the standard method (641 vs 424). The methods displayed a wide overlap, apart from 22 patients who were only recorded by the standard method. In these cases, the accompanying brain injury diagnosis was not recorded in the controlling and accounting unit data records due to little relative clinical significance. None of the 22 patients fulfilled the criteria for brain death. In summary, Transplant Check is an easy-to-use, reliable, and valid tool for evaluating donor potential in a maximum care hospital. Therefore from 2010 on, analyses were performed exclusively with Transplant Check at our university hospital.

Implementation of an In-House Innovation Learning Project

This paper reports on activities and results of a partnership approach to an in-house innovation learning project (ILP) that sought to leave a legacy of skills, expertise and experience to be retained and repeated in-house for participating owner-managed Small and Medium-sized Enterprises (SMEs). The project was geared at enhancing the competency, absorptive capacity, innovation capability, and technology transfer and licensing opportunities through engaging in activities that increased innovation capacity and organisational efficiency. The inclusion of activities for organisational efficiency was due to the fact that several SMEs in the eligible region did not have the preconditioned robust business foundations to effectively engage and harness the advantages of innovation. The project’s implementation took place between 2010 and 2013 and involved 90 owner-managed SMEs in three cohorts and three regions. These SMEs employed between six to 144 employees from various industrial sectors. Innovation consultants were contracted as facilitators, aided by specialist academics, in 12 half-day company sessions over a 12-month period in a hands-on ‘learning by doing’ customised process. This was also complemented by off-site practical learning workshops in innovation and skills development of three key people from each company, including the owner-manager. The paper tests and confirms significant improvements in sales, gross and net profits, innovation capacity, innovation skills and general business skills. A positive and significant relationship is also observed between sales turnover and the outputs of the innovation project.

The influence of project team relationships on cost growth

Purpose – Using projects executed with both traditional and integrated procurement methods, the study sought to investigate relationships that exist among project participants and the influence of those relationships on cost growth. The paper aims to discuss these issues. Design/methodology/approach – Questionnaires were administered among 274 construction projects located in 12 states including the Federal Capital Territory of Nigeria. Responses were obtained from 96 projects. Data were subjected to both descriptive and inferential analyses. Findings – In terms of cordiality, relationships between client and contractors ranked highest, while those among in-house project teams ranked lowest. Cost growth or cost overrun is significantly correlated with client-contractor relationship, consultant-contractor relationship, client-consultant-contractor relationship and in-house team relationships. No association between procurement method and cost growth was found. Research limitations/implications – The limitation of generalizability of results due to the sampling method used is acknowledged. One implication of the findings is that in the context of this research, any explanation for cost growth has to be found outside procurement methods. Practical implications – Findings may assist project participants on variables to consider in anticipating, preventing or managing cost growth in building construction projects, beyond formularization of contracts and structures. Originality/value – The research has uniquely investigated the association between intangible project team relationships and tangible variable of cost growth.

Characteristics and determinants of insourced and offshored projects: A comparative analysis

Similar in-house (or insourced) and offshored software development data were paired to find differences (if any) on four project performance criteria: project elapsed times, size, data quality, and same-source nations. For each paired project, the differences between five technical variables (development type, application type, architecture, development platform, and programming language) were considered. The resource dependency theory was used to examine the technical differences between matched projects. Additionally, Hofstede's cultural dimensions were used to analyze the performance of offshored software projects. Data from the International Software Benchmarking Standard Group (ISBSG) was used. The main empirical findings were as follows: project completion time is significantly shorter for in-house development projects; and firms prefer offshoring for new projects, client-service platforms, and newer application languages. Some of Hofstede's cultural dimensions do affect project quality and work effort for offshore projects.

A gradient-boosting approach for filtering de novo mutations in parent–offspring trios

Whole-genome and -exome sequencing on parent-offspring trios is a powerful approach to identifying disease-associated genes by detecting de novo mutations in patients. Accurate detection of de novo mutations from sequencing data is a critical step in trio-based genetic studies. Existing bioinformatic approaches usually yield high error rates due to sequencing artifacts and alignment issues, which may either miss true de novo mutations or call too many false ones, making downstream validation and analysis difficult. In particular, current approaches have much worse specificity than sensitivity, and developing effective filters to discriminate genuine from spurious de novo mutations remains an unsolved challenge. In this article, we curated 59 sequence features in whole genome and exome alignment context which are considered to be relevant to discriminating true de novo mutations from artifacts, and then employed a machine-learning approach to classify candidates as true or false de novo mutations. Specifically, we built a classifier, named De Novo Mutation Filter (DNMFilter), using gradient boosting as the classification algorithm. We built the training set using experimentally validated true and false de novo mutations as well as collected false de novo mutations from an in-house large-scale exome-sequencing project. We evaluated DNMFilter's theoretical performance and investigated relative importance of different sequence features on the classification accuracy. Finally, we applied DNMFilter on our in-house whole exome trios and one CEU trio from the 1000 Genomes Project and found that DNMFilter could be coupled with commonly used de novo mutation detection approaches as an effective filtering approach to significantly reduce false discovery rate without sacrificing sensitivity. The software DNMFilter implemented using a combination of Java and R is freely available from the website at http://humangenome.duke.edu/software.

Matched molecular pair-based data sets for computer-aided medicinal chemistry

Matched molecular pairs (MMPs) are widely used in medicinal chemistry to study changes in compound properties including biological activity, which are associated with well-defined structural modifications. Herein we describe up-to-date versions of three MMP-based data sets that have originated from in-house research projects. These data sets include activity cliffs, structure-activity relationship (SAR) transfer series, and second generation MMPs based upon retrosynthetic rules. The data sets have in common that they have been derived from compounds included in the ChEMBL database (release 17) for which high-confidence activity data are available. Thus, the activity data associated with MMP-based activity cliffs, SAR transfer series, and retrosynthetic MMPs cover the entire spectrum of current pharmaceutical targets. Our data sets are made freely available to the scientific community.

Matched molecular pair-based data sets for computer-aided medicinal chemistry

Matched molecular pairs (MMPs) are widely used in medicinal chemistry to study changes in compound properties including biological activity, which are associated with well-defined structural modifications. Herein we describe up-to-date versions of three MMP-based data sets that have originated from in-house research projects. These data sets include activity cliffs, structure-activity relationship (SAR) transfer series, and second generation MMPs based upon retrosynthetic rules. The data sets have in common that they have been derived from compounds included in the latest release of the ChEMBL database for which high-confidence activity data are available. Thus, the activity data associated with MMP-based activity cliffs, SAR transfer series, and retrosynthetic MMPs cover the entire spectrum of current pharmaceutical targets. Our data sets are made freely available to the scientific community.

적도태평양 도서국과의 협력 활성화를 위한 연구 인프라 구축

Until recently, Pacific equatorial tropical island states were subject of only very limited interest by scientists, government officials, industry and policy makers of Korea. And, comprehensive information and data on these island regions is not very detailed to help better understand their social backgrounds as well as their natural environment. However, these island regions are now in the middle of diplomatic tug-ofwar among super powers as well as becoming nucleus of various science-based ocean issues including marine biodiversity, shifting ecosystem, global environmental change including sea level rise and ocean acidification, fisheries, etc. Therefore, rising political and scientific importance of these areas call for better understanding of these regions, in social aspects as well as natural scientific knowledge of the region. To be provocatively prepared to more actively role in these regions, “A study on Establishing Research Infrastructures in the Tropical Pacific” has been supported during 2012-2013 as a mission-oriented in-house project of the KIOST. This project aims to provide various research infrastructure for Pacific island states, to reinforce cooperation with these nations, and to enhance Korea's national prestige. This special issue contains 10 research articles based on the studies conducted in 2012~2013.

CSAR Data Set Release 2012: Ligands, Affinities, Complexes, and Docking Decoys

A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) has collected several data sets from industry and added in-house data sets that may be used for this purpose (www.csardock.org). CSAR has currently obtained data from Abbott, GlaxoSmithKline, and Vertex and is working on obtaining data from several others. Combined with our in-house projects, we are providing a data set consisting of 6 protein targets, 647 compounds with biological affinities, and 82 crystal structures. Multiple congeneric series are available for several targets with a few representative crystal structures of each of the series. These series generally contain a few inactive compounds, usually not available in the literature, to provide an upper bound to the affinity range. The affinity ranges are typically 3–4 orders of magnitude per series. For our in-house projects, we have had compounds synthesized for biological testing. Affinities were measured by Thermofluor, Octet RED, and isothermal titration calorimetry for the most soluble. This allows the direct comparison of the biological affinities for those compounds, providing a measure of the variance in the experimental affinity. It appears that there can be considerable variance in the absolute value of the affinity, making the prediction of the absolute value ill-defined. However, the relative rankings within the methods are much better, and this fits with the observation that predicting relative ranking is a more tractable problem computationally. For those in-house compounds, we also have measured the following physical properties: logD, logP, thermodynamic solubility, and pKa. This data set also provides a substantial decoy set for each target consisting of diverse conformations covering the entire active site for all of the 58 CSAR-quality crystal structures. The CSAR data sets (CSAR-NRC HiQ and the 2012 release) provide substantial, publically available, curated data sets for use in parametrizing and validating docking and scoring methods.