From phenotype to genotype: issues in navigating the available information resources

pre-printObjectives-As part of an investigation of connecting health professionals and the lay public to both disease and genomic information, we assessed the availability and nature of the data from the Human Genome Project relating to human genetic diseases. Methods-We focused on a set of single gene diseases selected from main topics in MEDLINEplus, the NLM's principal resource focused on consumers. We used publicly available websites to investigate specific questions about the genes and gene products associated with the diseases. We also investigated questions of knowledge and data representation for the information resources and navigational issues. Results-Many online resources are available but they are complex and technical. The major challenges encountered when navigating from phenotype to genotype were (1) complexity of the data, (2) dynamic nature of the data, (3) diversity of foci and number of information resources, and (4) lack of use of standard data and knowledge representation methods. Conclusions-Three major informatics issues arise from the navigational challenges. First, the official gene names are insufficient for navigation of these web resources. Second, navigational inconsistencies arise from difficulties in determining the number and function of alternate forms of the gene or gene product and maintaining currency with this information. Third, synonymy and polysemy cause much confusion. These are severe obstacles to computational navigation from phenotype to genotype, especially for individuals who are novices in the underlying science. Tools and standards to facilitate this navigation are sorely needed

Electrolyte jet machining for surface texturing of Inconel 718

Electrolyte jet machining is an emerging non-conventional machining process which is capable of selectively applying multi-scale surface textures. Surfaces processed in this way do not suffer from thermal damage and hence this technique is highly suited to finishing procedures in high value manufacturing across the aerospace and biomedical sectors. Furthermore, input variables can be modified dynamically to create functional graduation across component surfaces. In this study, the development and design of a custom-built EJM system is described, and the capability of the EJM platform to machine and create surface textures in Inconel 718, a widely used nickel based super alloy, is investigated. Through control of machine path programming and parameter variation, multi-scale surface textures are created which have the potential to enhance bonding with subsequent coating layers and also provide fluid dynamic advantage

Chaos and isospin symmetry breaking in rotational nuclei

For nuclei with N = Z, the isospin degree of freedom is important and, for deformed systems, rotational bands of different isospin may be expected at low excitation energies. We have investigated, in a simple model space, the influence of the isospin-breaking Coulomb interaction on the degree of chaoticity of these rotational bands. The statistical measures used rely on an analysis of level-spacing distributions, which are extremely difficult to measure experimentally. We show, however, that the overlap intergrals between states of similar frequency reflect well the degree of chaoticity. This quantity is closely related to the experimentally more accessible gamma-decay ``spreading width''.Comment: 13 pages, 9 figures, Elsevie

Transitory electrochemical masking for precision jet processing techniques

Electrochemical jet processing techniques provide an efficient method for large area surface structuring and micro-milling, where the metallurgy of the near-surface is assured and not adversely affected by thermal loading. Here, doped electrolytes are specifically developed for jet techniques to exploit the Gaussian energy distribution as found in energy beam processes. This allows up to 26% reduction in dissolution kerf and enhancements of the defined precision metric of up to 284% when compared to standard electrolytes. This is achieved through the filtering of low energy at discrete points within the energy distribution curve. Two fundamental mechanisms of current filtering and refresh rate are proposed and investigated in order to underpin the performance enhancements found using this methodology. This study aims to demonstrate that a step change in process fidelity and flexibility can be achieved through optimisation of the electrochemistry specific to jet processes

Traumatic thoracic ASIA A examinations and potential for clinical trials

Study Design: Retrospective review of prospective database Objectives: To define the variability of neurologic examination and recovery after non-penetrating complete thoracic spinal cord injuries (ASIA A). Background Data: Neurologic examinations after SCI can be difficult and inconsistent. Unlike cervical SCI patients, alterations in thoracic (below T1) complete SCI (ASIA A – based on the ASIA Impairment Scale [AIS]) patients’ exams are based only on sensory testing, thus changes in the neurological level (NL) are determined only by sensory changes. Methods: A retrospective review of the placebo control patients in a multicenter prospective database utilized for the pharmacologic trial of Sygen. Patients were included if they had a complete thoracic SCI on initial evaluation, with completed ASIA examinations at follow-up weeks 4, 8, 16, 26 and 52. Specifically, pin prick (PP) and light touch (LT) were assessed and the absolute change was calculated as the number of spinal levels at a given observation time. Results 3165 patients were initially screened for the Sygen clinical trial, of which 57 were the control placebo patients used in this analysis. Alterations from the baseline exam (PP and LT) were fairly consistent and the median change/recovery in neurologic examination was one spinal level. Across all observations post-baseline, the average change for PP was 1.48 +/- 0.13 (mean +/- SE), and for LT, 1.40 +/-0.13. There were equal proportions of directional changes (none, improved, lost). Conclusions: Changes in a thoracic complete (ASIA A) SCI patient ASIA examination as measured through sensory modalities (PP/LT) are fairly uncommon. The overall examination had only 1-2 level variability across patients, indicating minimal change in the sensory exam over the follow-up period. Stability in the ASIA examination as measured through sensory modalities has thus been demonstrated over time, making it an excellent tool to monitor changes in neurologic function

Advancing electrochemical jet methods through manipulation of the angle of address

Electrochemical jet processing techniques have traditionally been considered to be limited to planar interactions with the electrolyte jet being maintained normal to the workpiece surface. In this study, the viability and resultant effects of articulating the nozzle relative to the work were investigated for the first time. Two machining conventions were defined, normal, where the jet is maintained perpendicular to the traverse direction, and push/pull, where the nozzle is rotated with respect to the direction of travel. It was found, with the normal convention that a range of differing resultant profile surface geometries could be created; unique to this process. This was demonstrated by the changing resultant side wall slopes found through the rotation of the head with up to 80% difference between the slopes of the cut walls. The adjacent wall to the nozzle slope decreasing as the jet angle approaches 90° whilst the opposite side wall slope increases. Predictable ratios of the differing slopes of the striation side walls were then able to be defined. The push/pull convention demonstrated that deeper, sharper cuts are possible due to the highly localising current density effect of nozzle inclination achieving a 35% increase in depth without requiring additional energy. Also, that resultant surface finish could be greatly improved, reducing the profile roughness (Ra) from 0.2 μm in the pull mode to 0.04 μm in the push mode achieving a mirror-like finish. The mechanics of these phenomena are investigated and defined. The influence of nozzle jet speed variation combined with inclining the jet was also studied. This was found to have no noticeable influence on the resultant profile when the nozzle is inclined. In contrast, when the nozzle is normal to the surface, jet velocity is seen to have a direct influence due to polarisation effects relating to the poor clearance of machining debris and the formation of oxides. It is shown that through variation of the angle of jet address an extra level of flexibility and performance is possible within electrochemical jet processes

Effects of clarithromycin at sub-minimum inhibitory concentrations on early ermB gene expression, metabolic activity and growth of an erm(B)-expressing macrolide-resistant strain of Streptococcus pneumoniae

AIM: To investigate the effects of exposure of a macrolide-resistant [erm(B)-expressing] strain of Streptococcus pneumo- niae (strain 2507) to clarithromycin (0.5 and 5 mg/L) added at the outset and 6 hours after initiation of culture on early gene expression, energy metabolism, and growth. METHODS: Bacterial growth was determined by turbidometric and colony counting procedures, energy metabolism by measurement of ATP, while analysis of gene expression was per- formed using reverse transcription-PCR and sequencing. RESULTS: Addition of clarithromycin, at either concentration, at the outset of culture, caused transient suppression of growth of 10 - 12 hours duration, while delayed addition of antibi-otic (during the logarithmic phase) resulted in an abrupt halt in growth followed by recovery. These inhibitory effects of clarithromycin on bacterial growth were associated with up-regulation of expression of erm(B), decreased ATP and protein synthesis, and were unaffected by inclusion of either catalase (500 and 1000 kunits/L), or compe- tence-stimulating peptide (CSP-1, 0.5 mg/L). The inhibitory effects could, however, be overcome by pre-exposure of the bacteria to the antibiotic. Moreover, clarithromycin appeared to potentiate the antimicrobial actions of ceftriaxone, at sub-MIC concentrations, for strain 2507. CONCLUSIONS: Unlike several other common bacterial pathogens, the full expression of erm(B)-mediated macrolide resistance by the pneumococcus has a slow onset, which is associated with transient susceptibility to macrolides and inhibition of growth.CF is supported by the National Research Foundation of South Africa.http://www.SciRP.org/journal/ojr