Embedding Languages Without Breaking Tools

Domain-specific languages (DSLs) are increasingly used as embedded languages within general-purpose host languages. DSLs provide a compact, dedicated syntax for specifying parts of an application related to specialized domains. Unfortunately, such language extensions typically do not integrate well with the development tools of the host language. Editors, compilers and debuggers are either unaware of the extensions, or must be adapted at a non-trivial cost. We present a novel approach to embed DSLs into an existing host language by leveraging the underlying representation of the host language used by these tools. Helvetia is an extensible system that intercepts the compilation pipeline of the Smalltalk host language to seamlessly integrate language extensions. We validate our approach by case studies that demonstrate three fundamentally different ways to extend or adapt the host language syntax and semantics.

Performance Characteristics of Airlift Pumps with Vortex Induced by Tangential Fluid Injection

The effect of the swirl component of air injection on the performance of an airlift pump was examined experimentally. An airlift pump is a device that pumps a liquid or slurry using only gas injection. In this study, the liquid used was water and the injected gas was air. The effect of the air swirl was determined by measuring the water discharge from an airlift pump with an air injection nozzle in which the air flow had both axial and tangential components and then repeating the tests with a nozzle with only axial injection. The induced water flow was measured using an orifice meter in the supply pipeline. Tests were run for air pressures ranging from 10 to 30 pounds per square inch, gauge (psig), at flow rates from 5 standard cubic feet per minute (scfm) up the maximum values attainable at the given pressure (usually in the range from 20 to 35 scfm). The nozzle with only axial injection produced a water flow rate that wasequivalent to or better than that induced by the nozzle with swirl. The swirl component of air injection was found to be detrimental to pump performance for all but the smallest air injection flow rate. Optimum efficiency was found for air injection pressures of 10 psig to 15 psig. In addition, the effect of using auxiliary tangential injection of water to create a swirl component in the riser before air injection on the overall capacity (i.e., flow rate) and efficiencyof the pump was examined. Auxiliary tangential water injection was found to have no beneficial effect on the pump capacity or performance in the present system.

Metabolomics reveals attenuation of the SLC6A20 kidney transporter in nonhuman primate and mouse models of type 2 diabetes mellitus

To enhance understanding of the metabolic indicators of type 2 diabetes mellitus (T2DM) disease pathogenesis and progression, the urinary metabolomes of well characterized rhesus macaques (normal or spontaneously and naturally diabetic) were examined. High-resolution ultra-performance liquid chromatography coupled with the accurate mass determination of time-of-flight mass spectrometry was used to analyze spot urine samples from normal (n = 10) and T2DM (n = 11) male monkeys. The machine-learning algorithm random forests classified urine samples as either from normal or T2DM monkeys. The metabolites important for developing the classifier were further examined for their biological significance. Random forests models had a misclassification error of less than 5%. Metabolites were identified based on accurate masses (<10 ppm) and confirmed by tandem mass spectrometry of authentic compounds. Urinary compounds significantly increased (p < 0.05) in the T2DM when compared with the normal group included glycine betaine (9-fold), citric acid (2.8-fold), kynurenic acid (1.8-fold), glucose (68-fold), and pipecolic acid (6.5-fold). When compared with the conventional definition of T2DM, the metabolites were also useful in defining the T2DM condition, and the urinary elevations in glycine betaine and pipecolic acid (as well as proline) indicated defective re-absorption in the kidney proximal tubules by SLC6A20, a Na(+)-dependent transporter. The mRNA levels of SLC6A20 were significantly reduced in the kidneys of monkeys with T2DM. These observations were validated in the db/db mouse model of T2DM. This study provides convincing evidence of the power of metabolomics for identifying functional changes at many levels in the omics pipeline.

Time-lapse microscopy and classification of 2D human mesenchymal stem cells based on cell shape picks up myogenic from osteogenic and adipogenic differentiation

Current methods to characterize mesenchymal stem cells (MSCs) are limited to CD marker expression, plastic adherence and their ability to differentiate into adipogenic, osteogenic and chondrogenic precursors. It seems evident that stem cells undergoing differentiation should differ in many aspects, such as morphology and possibly also behaviour; however, such a correlation has not yet been exploited for fate prediction of MSCs. Primary human MSCs from bone marrow were expanded and pelleted to form high-density cultures and were then randomly divided into four groups to differentiate into adipogenic, osteogenic chondrogenic and myogenic progenitor cells. The cells were expanded as heterogeneous and tracked with time-lapse microscopy to record cell shape, using phase-contrast microscopy. The cells were segmented using a custom-made image-processing pipeline. Seven morphological features were extracted for each of the segmented cells. Statistical analysis was performed on the seven-dimensional feature vectors, using a tree-like classification method. Differentiation of cells was monitored with key marker genes and histology. Cells in differentiation media were expressing the key genes for each of the three pathways after 21 days, i.e. adipogenic, osteogenic and chondrogenic, which was also confirmed by histological staining. Time-lapse microscopy data were obtained and contained new evidence that two cell shape features, eccentricity and filopodia (= 'fingers') are highly informative to classify myogenic differentiation from all others. However, no robust classifiers could be identified for the other cell differentiation paths. The results suggest that non-invasive automated time-lapse microscopy could potentially be used to predict the stem cell fate of hMSCs for clinical application, based on morphology for earlier time-points. The classification is challenged by cell density, proliferation and possible unknown donor-specific factors, which affect the performance of morphology-based approaches. Copyright © 2012 John Wiley & Sons, Ltd.

Intervertebral disc regeneration or repair with biomaterials and stem cell therapy--feasible or fiction?

The "gold standard" for treatment of intervertebral disc herniations and degenerated discs is still spinal fusion, corresponding to the saying "no disc - no pain". Mechanical prostheses, which are currently implanted, do only have medium outcome success and have relatively high re-operation rates. Here, we discuss some of the biological intervertebral disc replacement approaches, which can be subdivided into at least two classes in accordance to the two different tissue types, the nucleus pulposus (NP) and the annulus fibrosus (AF). On the side of NP replacement hydrogels have been extensively tested in vitro and in vivo. However, these gels are usually a trade-off between cell biocompatibility and load-bearing capacity, hydrogels which fulfill both are still lacking. On the side of AF repair much less is known and the question of the anchoring of implants is still to be addressed. New hope for cell therapy comes from developmental biology investigations on the existence of intervertebral disc progenitor cells, which would be an ideal cell source for cell therapy. Also notochordal cells (remnants of the embryonic notochord) have been recently pushed back into focus since these cells have regenerative potential and can activate disc cells. Growth factor treatment and molecular therapies could be less problematic. The biological solutions for NP and AF replacement are still more fiction than fact. However, tissue engineering just scratched the tip of the iceberg, more satisfying solutions are yet to be added to the biomedical pipeline.

Generation and analysis of a mouse intestinal metatranscriptome through Illumina based RNA-sequencing

With the advent of high through-put sequencing (HTS), the emerging science of metagenomics is transforming our understanding of the relationships of microbial communities with their environments. While metagenomics aims to catalogue the genes present in a sample through assessing which genes are actively expressed, metatranscriptomics can provide a mechanistic understanding of community inter-relationships. To achieve these goals, several challenges need to be addressed from sample preparation to sequence processing, statistical analysis and functional annotation. Here we use an inbred non-obese diabetic (NOD) mouse model in which germ-free animals were colonized with a defined mixture of eight commensal bacteria, to explore methods of RNA extraction and to develop a pipeline for the generation and analysis of metatranscriptomic data. Applying the Illumina HTS platform, we sequenced 12 NOD cecal samples prepared using multiple RNA-extraction protocols. The absence of a complete set of reference genomes necessitated a peptide-based search strategy. Up to 16% of sequence reads could be matched to a known bacterial gene. Phylogenetic analysis of the mapped ORFs revealed a distribution consistent with ribosomal RNA, the majority from Bacteroides or Clostridium species. To place these HTS data within a systems context, we mapped the relative abundance of corresponding Escherichia coli homologs onto metabolic and protein-protein interaction networks. These maps identified bacterial processes with components that were well-represented in the datasets. In summary this study highlights the potential of exploiting the economy of HTS platforms for metatranscriptomics.

Gene expression in cortex and hippocampus during acute pneumococcal meningitis

BACKGROUND: Pneumococcal meningitis is associated with high mortality (approximately 30%) and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown.We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i) a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI) and (ii) the self-organizing map (SOM), a clustering technique based on covariance in gene expression kinetics. RESULTS: Among 598 genes differentially regulated (change factor > or = 1.5; p < or = 0.05), 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. CONCLUSION: Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential targets for therapy.

Comparison of common dredging equipment air emissions

The purpose of this study is to provide a procedure to include emissions to the atmosphere resulting from the combustion of diesel fuel during dredging operations into the decision-making process of dredging equipment selection. The proposed procedure is demonstrated for typical dredging methods and data from the Illinois Waterway as performed by the U.S. Army Corps of Engineers, Rock Island District. The equipment included in this study is a 16-inch cutterhead pipeline dredge and a mechanical bucket dredge used during the 2005 dredging season on the Illinois Waterway. Considerable effort has been put forth to identify and reduce environmental impacts from dredging operations. Though environmental impacts of dredging have been studied no efforts have been applied to the evaluation of air emissions from comparable types of dredging equipment, as in this study. By identifying the type of dredging equipment with the lowest air emissions, when cost, site conditions, and equipment availability are comparable, adverse environmental impacts can be minimized without compromising the dredging project. A total of 48 scenarios were developed by varying the dredged material quantity, transport distance, and production rates. This produced an “envelope” of results applicable to a broad range of site conditions. Total diesel fuel consumed was calculated using standard cost estimating practices as defined in the U.S. Army Corps of Engineers Construction Equipment Ownership and Operating Expense Schedule (USACE, 2005). The diesel fuel usage was estimated for all equipment used to mobilize and/or operate each dredging crew for every scenario. A Limited Life Cycle Assessment (LCA) was used to estimate the air emissions from two comparable dredging operations utilizing SimaPro LCA software. An Environmental Impact Single Score (EISS) was the SimaPro output selected for comparison with the cost per CY of dredging, potential production rates, and transport distances to identify possible decision points. The total dredging time was estimated for each dredging crew and scenario. An average hourly cost for both dredging crews was calculated based on Rock Island District 2005 dredging season records (Graham 2007/08). The results from this study confirm commonly used rules of thumb in the dredging industry by indicating that mechanical bucket dredges are better suited for long transport distances and have lower air emissions and cost per CY for smaller quantities of dredged material. In addition, the results show that a cutterhead pipeline dredge would be preferable for moderate and large volumes of dredged material when no additional booster pumps are required. Finally, the results indicate that production rates can be a significant factor when evaluating the air emissions from comparable dredging equipment.

Systemic analysis of microarray data sets towards identifying genes regulating root development

Nitrogen and water are essential for plant growth and development. In this study, we designed experiments to produce gene expression data of poplar roots under nitrogen starvation and water deprivation conditions. We found low concentration of nitrogen led first to increased root elongation followed by lateral root proliferation and eventually increased root biomass. To identify genes regulating root growth and development under nitrogen starvation and water deprivation, we designed a series of data analysis procedures, through which, we have successfully identified biologically important genes. Differentially Expressed Genes (DEGs) analysis identified the genes that are differentially expressed under nitrogen starvation or drought. Protein domain enrichment analysis identified enriched themes (in same domains) that are highly interactive during the treatment. Gene Ontology (GO) enrichment analysis allowed us to identify biological process changed during nitrogen starvation. Based on the above analyses, we examined the local Gene Regulatory Network (GRN) and identified a number of transcription factors. After testing, one of them is a high hierarchically ranked transcription factor that affects root growth under nitrogen starvation. It is very tedious and time-consuming to analyze gene expression data. To avoid doing analysis manually, we attempt to automate a computational pipeline that now can be used for identification of DEGs and protein domain analysis in a single run. It is implemented in scripts of Perl and R.

BALTHMETRIC SURVEY IN THE KEWEENAW WATER WAY IN MICHIGAN, USA, MAKING 3D MODEL, AND COMPARING SONAR EQUIPMENT OF THE MODERN AUV AND THE TRADITIONAL SINGLE BEAM SONAR

This thesis represents the overview of hydrographic surveying and different types of modern and traditional surveying equipment, and data acquisition using the traditional single beam sonar system and a modern fully autonomous underwater vehicle, IVER3. During the thesis, the data sets were collected using the vehicles of the Great Lake Research Center at Michigan Technological University. This thesis also presents how to process and edit the bathymetric data on SonarWiz5. Moreover, the three dimensional models were created after importing the data sets in the same coordinate system. In these interpolated surfaces, the details and excavations can be easily seen on the surface models. In this study, the profiles are plotted on the surface models to compare the sensors and details on the seabed. It is shown that single beam sonar might miss some details, such as pipeline and quick elevation changes on the seabed when we compare to the side scan sonar of IVER3 because the single side scan sonar can acquire better resolution. However, sometimes using single beam sonar can save your project time and money because the single beam sonar is cheaper than side scan sonars and the processing might be easier than the side scan data.

EXHAUST EMISSIONS OF LOW LEVEL BLEND ALCOHOL FUELS FROM TWO-STROKE AND FOUR-STROKE MARINE ENGINES

The U.S. Renewable Fuel Standard mandates that by 2022, 36 billion gallons of renewable fuels must be produced on a yearly basis. Ethanol production is capped at 15 billion gallons, meaning 21 billion gallons must come from different alternative fuel sources. A viable alternative to reach the remainder of this mandate is iso-butanol. Unlike ethanol, iso-butanol does not phase separate when mixed with water, meaning it can be transported using traditional pipeline methods. Iso-butanol also has a lower oxygen content by mass, meaning it can displace more petroleum while maintaining the same oxygen concentration in the fuel blend. This research focused on studying the effects of low level alcohol fuels on marine engine emissions to assess the possibility of using iso-butanol as a replacement for ethanol. Three marine engines were used in this study, representing a wide range of what is currently in service in the United States. Two four-stroke engine and one two-stroke engine powered boats were tested in the tributaries of the Chesapeake Bay, near Annapolis, Maryland over the course of two rounds of weeklong testing in May and September. The engines were tested using a standard test cycle and emissions were sampled using constant volume sampling techniques. Specific emissions for two-stroke and four-stroke engines were compared to the baseline indolene tests. Because of the nature of the field testing, limited engine parameters were recorded. Therefore, the engine parameters analyzed aside from emissions were the operating relative air-to-fuel ratio and engine speed. Emissions trends from the baseline test to each alcohol fuel for the four-stroke engines were consistent, when analyzing a single round of testing. The same trends were not consistent when comparing separate rounds because of uncontrolled weather conditions and because the four-stroke engines operate without fuel control feedback during full load conditions. Emissions trends from the baseline test to each alcohol fuel for the two-stroke engine were consistent for all rounds of testing. This is due to the fact the engine operates open-loop, and does not provide fueling compensation when fuel composition changes. Changes in emissions with respect to the baseline for iso-butanol were consistent with changes for ethanol. It was determined iso-butanol would make a viable replacement for ethanol.

Automatic Data Normalization and Parameterization for Optical Motion Tracking

Methods for optical motion capture often require timeconsuming manual processing before the data can be used for subsequent tasks such as retargeting or character animation. These processing steps restrict the applicability of motion capturing especially for dynamic VR-environments with real time requirements. To solve these problems, we present two additional, fast and automatic processing stages based on our motion capture pipeline presented in [HSK05]. A normalization step aligns the recorded coordinate systems with the skeleton structure to yield a common and intuitive data basis across different recording sessions. A second step computes a parameterization based on automatically extracted main movement axes to generate a compact motion description. Our method does not restrict the placement of marker bodies nor the recording setup, and only requires a short calibration phase.

VR Based Visualization and Exploration of Plant Biological Data

This paper investigates the use of virtual reality (VR) technologies to facilitate the analysis of plant biological data in distinctive steps in the application pipeline. Reconstructed three-dimensional biological models (primary polygonal models) transferred to a virtual environment support scientists' collaborative exploration of biological datasets so that they obtain accurate analysis results and uncover information hidden in the data. Examples of the use of virtual reality in practice are provided and a complementary user study was performed.

The Mycoplasma conjunctivae genome sequencing, annotation and analysis

BACKGROUND: The mollicute Mycoplasma conjunctivae is the etiological agent leading to infectious keratoconjunctivitis (IKC) in domestic sheep and wild caprinae. Although this pathogen is relatively benign for domestic animals treated by antibiotics, it can lead wild animals to blindness and death. This is a major cause of death in the protected species in the Alps (e.g., Capra ibex, Rupicapra rupicapra). METHODS: The genome was sequenced using a combined technique of GS-FLX (454) and Sanger sequencing, and annotated by an automatic pipeline that we designed using several tools interconnected via PERL scripts. The resulting annotations are stored in a MySQL database. RESULTS: The annotated sequence is deposited in the EMBL database (FM864216) and uploaded into the mollicutes database MolliGen http://cbi.labri.fr/outils/molligen/ allowing for comparative genomics. CONCLUSION: We show that our automatic pipeline allows for annotating a complete mycoplasma genome and present several examples of analysis in search for biological targets (e.g., pathogenic proteins).

[Mastitis management in Swiss dairy farms with udder health problems]

The objective of this study was to describe the udder health management in Swiss dairy herds with udder health problems. One hundred dairy herds with a yield-corrected somatic cell count of 200'000 to 300'000 cells/ml during 2010 were selected. Data concerning farm structure, housing system, milking technique, milking procedures, dry-cow and mastitis management were collected during farm visits between September and December 2011. In addition, quarter milk samples were collected for bacteriological culturing from cows with a composite somatic cell count ≥ 150'000 cells/ml. The highest quarter level prevalence was 12.3 % for C. bovis. Eighty-two percent of the pipeline milking machines in tie-stalls and 88 % of the milking parlours fulfilled the criteria for the vacuum drop, and only 74 % of the pipeline milking machines met the criteria of the 10-l-water test. Eighty-five percent of the farms changed their milk liners too late. The correct order of teat preparation before cluster attachment was carried out by 37 % of the farmers only. With these results, Swiss dairy farmers and herd health veterinarians can be directed to common mistakes in mastitis management. The data will be used for future information campaigns to improve udder health in Swiss dairy farms.