Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports.

Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5β-androstane-3α,17β-diol and 5α-androstane-3α,17β-diol/5β-androstane-3α,17β-diol as best biomarkers for DHT administration and DHEA/E, 16α-hydroxydehydroepiandrosterone/E, 7β-hydroxydehydroepiandrosterone/E and 5β-androstane-3α,17β-diol/5α-androstane-3α,17β-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained.The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids. Copyright © 2010 John Wiley & Sons, Ltd.

Report on selected computer systems operated by the State of Iowa for the period July 1, 1999 through June 30, 2014

Report on selected computer systems operated by the State of Iowa for the period July 1, 1999 through June 30, 2014

Education on Urban Corridor Issues Through Computer Animation, TR-419, 2003

This project was undertaken in coordination with the Environmental Assessment process on the Mt. Vernon Road Improvements project in Cedar Rapids, Iowa. The goal of the research was to determine the cost effectiveness of combined photo-imaging and computer animation as a presentation tool describing public road improvements. The Public Hearing, in combination with the involvement of a Citizen's Resource Group, afforded an opportunity to have an evaluation of the processes by interested citizens who were not familiar with engineering drawings or the construction industry. After the initial viewing of a draft version of the video, the Resource Group made recommendations to the staff developing the video. Discussion of these recommendations led to the development of an animated composite section that showed a combination of situations typically encountered throughout the project corridor, as well as critical considerations. The composite section did not show specific locations and therefore, individuals were not distracted by looking for the details pertaining to their properties. Concentration on the concepts involved rather than specifics provided the opportunity for a more thorough understanding by the citizens. The development of the composite concept was the primary discovery of the research.

Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers.

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

Comparison of Roadway Roughness Derived from LIDAR and SFM 3D Point Clouds, HR-3001, 2015

This report describes a short-term study undertaken to investigate the potential for using dense three-dimensional (3D) point clouds generated from light detection and ranging (LIDAR) and photogrammetry to assess roadway roughness. Spatially continuous roughness maps have potential for the identification of localized roughness features, which would be a significant improvement over traditional profiling methods. This report specifically illustrates the use of terrestrial laser scanning (TLS) and photogrammetry using a process known as structure from motion (SFM) to acquire point clouds and illustrates the use of these point clouds in evaluating road roughness. Five roadway sections were chosen for scanning and testing: three gravel road sections, one portland cement concrete (PCC) section, and one asphalt concrete (AC) section. To compare clouds obtained from terrestrial laser scanning and photogrammetry, the coordinates of the clouds for the same section on the same date were matched using open source computer code. The research indicates that the technologies described are very promising for evaluating road roughness. The major advantage of both technologies is the large amount of data collected, which allows the evaluation of the full surface. Additional research is needed to further develop the use of dense 3D point clouds for roadway assessment.

Computer Aided Detection and measurement of peripheral artery disease.

Computer-Aided Tomography Angiography (CTA) images are the standard for assessing Peripheral artery disease (PAD). This paper presents a Computer Aided Detection (CAD) and Computer Aided Measurement (CAM) system for PAD. The CAD stage detects the arterial network using a 3D region growing method and a fast 3D morphology operation. The CAM stage aims to accurately measure the artery diameters from the detected vessel centerline, compensating for the partial volume effect using Expectation Maximization (EM) and a Markov Random field (MRF). The system has been evaluated on phantom data and also applied to fifteen (15) CTA datasets, where the detection accuracy of stenosis was 88% and the measurement accuracy was with an 8% error.

A biophysical model of atrial fibrillation ablation: what can a surgeon learn from a computer model?

AIMS: Surgical ablation procedures for treating atrial fibrillation have been shown to be highly successful. However, the ideal ablation pattern still remains to be determined. This article reports on a systematic study of the effectiveness of the performance of different ablation line patterns. METHODS AND RESULTS: This study of ablation line patterns was performed in a biophysical model of human atria by combining basic lines: (i) in the right atrium: isthmus line, line between vena cavae and appendage line and (ii) in the left atrium: several versions of pulmonary vein isolation, connection of pulmonary veins, isthmus line, and appendage line. Success rates and the presence of residual atrial flutter were documented. Basic patterns yielded conversion rates of only 10-25 and 10-55% in the right and the left atria, respectively. The best result for pulmonary vein isolation was obtained when a single closed line encompassed all veins (55%). Combination of lines in the right/left atrium only led to a success rate of 65/80%. Higher rates, up to 90-100%, could be obtained if right and left lines were combined. The inclusion of a left isthmus line was found to be essential for avoiding uncommon left atrial flutter. CONCLUSION: Some patterns studied achieved a high conversion rate, although using a smaller number of lines than those of the Maze III procedure. The biophysical atrial model is shown to be effective in the search for promising alternative ablation strategies.

Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines.

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients.

Detection and chemical profiling of medicine counterfeits by Raman spectroscopy and chemometrics

Raman spectroscopy combined with chemometrics has recently become a widespread technique for the analysis of pharmaceutical solid forms. The application presented in this paper is the investigation of counterfeit medicines. This increasingly serious issue involves networks that are an integral part of industrialized organized crime. Efficient analytical tools are consequently required to fight against it. Quick and reliable authentication means are needed to allow the deployment of measures from the company and the authorities. For this purpose a method in two steps has been implemented here. The first step enables the identification of pharmaceutical tablets and capsules and the detection of their counterfeits. A nonlinear classification method, the Support Vector Machines (SVM), is computed together with a correlation with the database and the detection of Active Pharmaceutical Ingredient (API) peaks in the suspect product. If a counterfeit is detected, the second step allows its chemical profiling among former counterfeits in a forensic intelligence perspective. For this second step a classification based on Principal Component Analysis (PCA) and correlation distance measurements is applied to the Raman spectra of the counterfeits.

Proteomic and transcriptomic profiling of Staphylococcus aureus surface LPXTG-proteins: correlation with agr genotypes and adherence phenotypes.

Staphylococcus aureus infections involve numerous adhesins and toxins, which expression depends on complex regulatory networks. Adhesins include a family of surface proteins covalently attached to the peptidoglycan via a conserved LPXTG motif. Here we determined the protein and mRNA expression of LPXTG-proteins of S. aureus Newman in time-course experiments, and their relation to fibrinogen adherence in vitro. Experiments were performed with mutants in the global accessory-gene regulator (agr), surface protein A (Spa), and fibrinogen-binding protein A (ClfA), as well as during growth in iron-rich or iron-poor media. Surface proteins were recovered by trypsin-shaving of live bacteria. Released peptides were analyzed by liquid chromatography coupled to tandem mass-spectrometry. To unambiguously identify peptides unique to LPXTG-proteins, the analytical conditions were refined using a reference library of S. aureus LPXTG-proteins heterogeneously expressed in surrogate Lactococcus lactis. Transcriptomes were determined by microarrays. Sixteen of the 18 LPXTG-proteins present in S. aureus Newman were detected by proteomics. Nine LPXTG-proteins showed a bell-shape agr-like expression that was abrogated in agr-negative mutants including Spa, fibronectin-binding protein A (FnBPA), ClfA, iron-binding IsdA, and IsdB, immunomodulator SasH, functionally uncharacterized SasD, biofilm-related SasG and methicillin resistance-related FmtB. However, only Spa and SasH modified their proteomic and mRNA profiles in parallel in the parent and its agr- mutant, whereas all other LPXTG-proteins modified their proteomic profiles independently of their mRNA. Moreover, ClfA became highly transcribed and active in fibrinogen-adherence tests during late growth (24 h), whereas it remained poorly detected by proteomics. On the other hand, iron-regulated IsdA-B-C increased their protein expression by >10-times in iron-poor conditions. Thus, proteomic, transcriptomic, and adherence-phenotype demonstrated differential profiles in S. aureus. Moreover, trypsin peptide signatures suggested differential protein domain exposures in various environments, which might be relevant for anti-adhesin vaccines. A comprehensive understanding of the S. aureus physiology should integrate all three approaches.

Computer Analysis of Twin Box Culverts, 1959

The paper presents a method of analyzing Rigid Frames by use of the Conjugate Beam Theory. The development of the method along with an example is given. This method has been used to write a computer program for the analysis of twin box culverts. The culverts may be analyzed under any fill height and any of the standard truck loadings. The wall and slab thickness are increased by the computer program as necessary. The final result is steel requirements both for moment and shear, and the slab and wall thickness.