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PubMed2006

Femoral revision with a fluted, tapered, modular stem seventy patients followed for a mean of 3.9 years.

Fluted tapered revision femoral stems have been used successfully in Europe. Modularity makes these implants more versatile, but outcomes of modular designs have not been reported. We report a retrospective review of 70 such stems with a mean follow-up of 47 months. Combined metaphyseal/diaphyseal bone loss was present preoperatively in 36 (51%) of 70 hips. Three hips (4.3%) were re-revised or in need of re-revision, and worst-case survival was 87%. The mean postoperative patient-assessed Oxford Hip Score was 21.1. Restoration of proximal bone was noted in 56%. Complications included mean subsidence of 9.9 mm, dislocation in 7 (10%) of 70 hips, and fracture or cortical perforation in 17 (24.2%) of 70. These results are equivalent to, or better than, reported results of other types of cementless revision femoral stems.

Adult↗

PubMed2006

Evidence for a protein-protein interaction motif on an acyl carrier protein domain from a modular polyketide synthase.

During biosynthesis on modular polyketide synthases (PKSs), chain extension intermediates are tethered to acyl carrier protein (ACP) domains through phosphopantetheinyl prosthetic groups. Each ACP must therefore interact with every other domain within the module, and also with a downstream acceptor domain. The nature of these interactions is key to our understanding of the topology and operation of these multienzymes. Sequence analysis and homology modeling implicates a potential helical region (helix II) on the ACPs as a protein-protein interaction motif. Using site-directed mutagenesis, we show that residues along this putative helix lie at the interface between the ACP and the phosphopantetheinyl transferase that catalyzes its activation. Our results accord with previous studies of discrete ACP proteins from fatty acid and aromatic polyketide biosynthesis, suggesting that helix II may also serve as a universal interaction motif in modular PKSs.

Acyl Carrier Protein↗

PubMed2005

Evaluation of the turnaround time of an integrated preanalytical and analytical automated modular system in a medium-sized laboratory.

OBJECTIVES: Evaluation of an integrated Modular Preanalytics (MPA) and Modular Analytics SWA (MA) system (Roche Diagnostics) during continuous batch processing. DESIGN AND METHODS: A total of 1000 blood specimen tubes was processed and tested in a batch-wise fashion, according to two different specimen input conditions (Study 1 and Study 2). The resulting turnaround time of the system was assessed. RESULTS: Study 1 tubes were centrifuged in the MPA. The preanalytical time rose steadily from 14 to 28 min, and after sample 315, it showed minimal variation. The analytical time remained almost constant. In Study 2, tubes were centrifuged before being processed in the MPA. The preanalytical time increased from 4 to 19 min, and the analytical time increased similarly. The turnaround time in Study 1 was 132 min and in Study 2 was 108 min. CONCLUSION: Centrifugation in the MPA slightly increased the turnaround time. Nevertheless, the labor associated with specimen processing was reduced and the efficiency of the laboratory was improved.

Autoanalysis↗

PubMed2006

Improved version of the printed circuit board (PCB) modular multi-channel microdrive for extracellular electrophysiological recordings.

The modular multi-channel PCB microdrive was described some years ago, since then several improvements were introduced while using these drives. Utilizing several years of experience with the original PCB microdrive we redesigned it to improve its stability and usability. The application of the printed circuit board technology and the extensive use of flexible fused silica capillaries for fabrication of the microdrive are described in detail. The improved design led to a low cost and light-weight multi-channel microdrive with outstanding modularity for extracellular field, single unit or multiunit tetrode recording up to 64/128 channels.

Electrodes, Implanted↗

PubMed2005

Fractures above and below a modular nail for knee arthrodesis. A case report.

Several techniques have been advocated for knee arthrodesis, and there has been an increasing interest in modular intramedullary nails in the recent last years. We report a case of femoral and tibial fractures at each end of a modular nail in a solidly fused knee 8 months after an arthrodesis.

Accidental Falls↗

PubMed2006

Long splice variant N type calcium channels are clustered at presynaptic transmitter release sites without modular adaptor proteins.

The presynaptic N type Ca channel (CaV2.2) is associated with the transmitter release site apparatus and plays a critical role in the gating of transmitter release. It has been suggested that a distinct CaV2.2 long C terminal splice variant is targeted to the nerve terminal and is anchored at the release face by calcium/calmodulin-dependent serine protein kinase (CASK) and Munc-18-interacting protein (MINT), two modular adaptor proteins. We used the isolated chick ciliary ganglion calyx terminal together with two new antibodies (L4569, L4570) selective for CaV2.2 long C terminal splice variant to test these hypotheses. CaV2.2 long C terminal splice variant was present at the presynaptic transmitter release sites, as identified by Rab3a-interacting molecule (RIM) co-staining and quantitative immunocytochemistry. CASK was also present at the terminal both in conjunction with, and independent of its binding partner, MINT. Immunoprecipitation of CaV2.2 long C terminal splice variant from brain lysate coprecipitated CASK, confirming that these two proteins can form a complex. However, CASK was not colocalized either with CaV2.2 long C terminal splice variant or the transmitter release site marker RIM at the calyx terminal release face. Neither was MINT colocalized with CaV2.2 long C terminal splice variant. Our results show that native CaV2.2 long C terminal splice variant is targeted to the transmitter release sites at an intact presynaptic terminal. However, the lack of enrichment of CASK at the release site combined with the failure of this protein or its partner MINT to colocalize with CaV2.2 argues against the idea that these modular adaptor proteins anchor CaV2.2 at presynaptic nerve terminals.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Is speech perception modular or interactive?

Norris et al. recently reported experimental evidence that listeners learn phoneme categories in response to lexical feedback. To reconcile these findings with their modular account of speech perception, the authors argue that top-down feedback can be used to support phoneme learning, but not to influence on-line phonemic processing. We suggest that these findings have broader implications than the authors assume, and we discuss potential challenges for integrating a modular theory with top-down learning.

Feedback↗

PubMed2004

Spatial interactions within modular organisms: genetic heterogeneity and organism fitness.

Modular organisms are composed of iterated units of construction that vary in their spatial arrangement. This variation is expected to affect the fitness of modular organisms due to interactions among neighboring modules and the potential for such organisms to be genetically heterogeneous. We devise a spatially explicit model to investigate how spatial interactions among neighboring modules affect organism fitness. We show that fitness is strongly dependent on the spatial arrangement of modules in both genetically homogeneous and heterogeneous organisms, and that the magnitude of the variation is dependent on the strength of interactions among modules. Organism fitness is more variable with interactions among modules that are symmetrical (each affects each other in the same directions) than with asymmetrical interactions (neighbors affect each other in different directions). We conclude by discussing potential extension of the present framework to a general dynamic model of spatially structured organism development.

Adaptation, Physiological↗

PubMed1998

Disorders of auditory processing: evidence for modularity in audition.

This article examines four disorders of auditory processing that can result from selective brain damage (cortical deafness, pure word deafness, auditory agnosia and phonagnosia) in an effort to derive a plausible functional and neuroanatomical model of audition. The article begins by identifying three possible reasons why models of auditory processing have been slower to emerge than models of visual processing: neuroanatomical differences between the visual and auditory systems, terminological confusions relating to auditory processing disorders, and technical factors that have made auditory stimuli more difficult to study than visual stimuli. The four auditory disorders are then reviewed and current theories of auditory processing considered. Taken together, these disorders suggest a modular architecture analogous to models of visual processing that have been derived from studying neurological patients. Ideas for future research to test modular theory more fully are presented.

Acoustic Stimulation↗

PubMed2001

A new modular testing system for biomechanical evaluation of tibial intramedullary fixation devices.

This biomechanical study was performed to evaluate a new modular, tibial testing system developed for analysis of tibial nails and their locking screws.A new testing system, consisting of five modules, was designed to simulate a tibia. For this study one module was removed to simulate a 55-mm distal tibial defect inducing maximum loading on the distal portion of the implant and locking bolts. The tibial load offsets were 23 mm proximally and 10 mm distally medial to the centreline of the tibial shaft to simulate the location of the expected resultant load during the peak loading and inversion torque on the ankle during the gait cycle. Four solid tibial nails (STN, Stryker-Howmedica-Osteonics, Kiel, Germany) were tested to static failure and 15 nails were tested dynamically. Our results showed that the solid tibial nails fractured in the testing device in the same manner and location as they do in clinical series. Evaluation of the results showed the mean fatigue limit of the STN to be 1.4 kN for 500,000 cycles with a standard deviation (S.D.) of 0.33 kN. This biomechanical study establishes a standard technique for the biomechanical testing of tibial nails, in a clinically relevant manner, avoiding the inconsistency of cadaver bone tests. As it is a standardised test set-up this new modular testing system could serve as a standard by which small diameter tibial nails and other devices could be evaluated and compared with other systems currently in use.

Biomechanical Phenomena↗

PubMed2000

Stress and micromotion in the taper lock joint of a modular segmental bone replacement prosthesis.

The stress distribution within the components and the micromotion of the interface significantly influence the long-term function of the taper lock joint in a modular segmental bone replacement prosthesis. Bending-induced gap opening between the cone and the sleeve can lead to an inflow of biological fluids, and thus accelerate implant corrosion. Local areas of high stress can also accelerate the corrosive processes and initiate local yielding, which may lead to a fracture in one of the components. In this study, a 3-D finite element (FE) model of a modular segmental bone replacement prosthesis was developed to study the interface micromotion and component stress distribution under the maximum loads applied during gait for a taper lock joint with multiple material combinations. Bending was the main cause of the local high stresses and interface separation within the taper joint. For Ti6A14V components, cortical bone bridging and ingrowth across the taper lock gap reduced the peak stress by 45% and reduced the contact interface separation by 55%. Such tissue formation around the taper lock joint could also form a closed capsule to restrict the migration of potential wear particles and thus prevent the biologic process of bone resorption induced by metal debris.

Bone and Bones↗

PubMed1998

Backside nonconformity and locking restraints affect liner/shell load transfer mechanisms and relative motion in modular acetabular components for total hip replacement.

Nonconformity between the polyethylene liner and the metal shell may exist in modular acetabular components by design, due to manufacturing tolerances, or from locking mechanisms that attach the polyethylene liner to the metal shell. Relative motion at the liner/shell interface has been associated with backside wear, which may contribute to osteolysis which has been clinically observed near screw holes. The purpose of this study was to investigate the effect of nonconformity and locking restraints on the liner/shell relative motion and load transfer mechanisms in a commercially available, metal-backed acetabular component with a polar fenestration. The finite element method was used to explore the hypothesis that backside nonconformity and locking restraints play important roles in long-term surface damage mechanisms that are unique to modular components, such as backside wear and liner extrusion through screw holes. The three-body quasi-static contact problem was solved using a commercially available explicit finite element code, which modeled contact between the femoral head, polyethylene liner, and the metal shell. Four sets of liner boundary conditions were investigated: no restraints, rim restraints, equatorial restraints, and both rim and equatorial restraints. The finite element model with a conforming shell predicted between 8.5 and 12.8 microm of incremental extrusion of the polyethylene through the polar fenestration, consistent with in vitro experiments of the same design under identical loading conditions. Furthermore, idealized rim and/or equatorial liner restraints were found to share up to 71% of the load across the liner/shell interface. Consequently, the results of this study demonstrate that backside nonconformity and locking restraints substantially influence backside relative motion as well as load transfer at the liner/shell interface.

Acetabulum↗

PubMed2002

Limits of cooperativity in a structurally modular protein: response of the Notch ankyrin domain to analogous alanine substitutions in each repeat.

To determine the limits of cooperativity in a structurally modular protein, we characterized the structure and stability of glycine variants of the ankyrin repeat domain from the Drosophila melangaster Notch receptor. The substitutions are of analogous alanine residues to glycine in each repeat, and allow the same perturbation to be examined at different positions in the protein. The ankyrin domain is insensitive to substitution in repeat one, suggesting that the first repeat is not fully-folded. Glycine substitutions in repeat two through seven are strongly destabilizing, but the variants retain their overall secondary and tertiary structures. Spectroscopic and calorimetric data are consistent with two-state unfolding transitions for the repeat-two through repeat-five glycine variants, and for the wild-type protein. These data indicate that, despite its modular structure, the Notch ankyrin domain unfolds as a cooperative unit consisting of the six C-terminal repeats, and that this cooperativity is maintained in the presence of severely destabilizing substitutions in the N-terminal and central repeats. In contrast, glycine substitution in repeat six leads to a multi-state unfolding transition, suggesting that the coupling that gives rise to long-range cooperativity in the wild-type protein may have a weak link in the C-terminal region. Such behavior is captured by a simple statistical thermodynamic model in which an unstable C-terminal region is coupled to a stable N-terminal region through a strongly stabilizing interface.

Alanine↗

PubMed2003

Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases.

Modular polyketide synthases (PKSs) are large multi-enzymatic, multi-domain megasynthases, which are involved in the biosynthesis of a class of pharmaceutically important natural products, namely polyketides. These enzymes harbor a set of repetitive active sites termed modules and the domains present in each module dictate the chemical moiety that would add to a growing polyketide chain. This modular logic of biosynthesis has been exploited with reasonable success to produce several novel compounds by genetic manipulation. However, for harnessing their vast potential of combinatorial biosynthesis, it is essential to develop knowledge based in silico approaches for correlating the sequence and domain organization of PKSs to their polyketide products. In this work, we have carried out extensive sequence analysis of experimentally characterized PKS clusters to develop an automated computational protocol for unambiguous identification of various PKS domains in a polypeptide sequence. A structure based approach has been used to identify the putative active site residues of acyltransferase (AT) domains, which control the specificities for various starter and extender units during polyketide biosynthesis. On the basis of the analysis of the active site residues and molecular modelling of substrates in the active site of representative AT domains, we have identified a crucial residue that is likely to play a major role in discriminating between malonate and methylmalonate during selection of extender groups by this domain. Structural modelling has also explained the experimentally observed chiral preference of AT domain in substrate selection. This computational protocol has been used to predict the domain organization and substrate specificity for PKS clusters from various microbial genomes. The results of our analysis as well as the computational tools for prediction of domain organization and substrate specificity have been organized in the form of a searchable computerized database (PKSDB). PKSDB would serve as a valuable tool for identification of polyketide products biosynthesized by uncharacterized PKS clusters. This database can also provide guidelines for rational design of experiments to engineer novel polyketides.

Amino Acid Sequence↗

PubMed1976

Modular Formula: an approach to management of infants with specific or complex food intolerances.

Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.

Diarrhea, Infantile↗

PubMed2006

The International Consultation on Incontinence Modular Questionnaire: www.iciq.net.

PURPOSE: In 1998 the first ICI was held in Monaco, sponsored by WHO and organized by the International Continence Society and International Consultation on Urological Diseases. The Scientific Committee recognized the need to develop a universally applicable questionnaire for wide application across international populations in clinical practice and research to assess urinary incontinence, facilitating the comparison of findings from different settings and studies, in a manner similar to the International Prostate Symptom Score. MATERIALS AND METHODS: An Advisory Board was formed to steer the development of the ICIQ and a decision was made to extend the concept further, developing the ICIQ Modular Questionnaire. RESULTS: The first module developed was the ICIQ Short Form Questionnaire for urinary incontinence. ICIQ modules have been developed or adapted for urinary tract symptoms and they are being developed for vaginal and lower bowel symptoms. Additional sexual matters and quality of life modules will become available for each condition area. Modules to assess patient satisfaction are expected to be of particular use for assessing treatment effectiveness. The ICIQ Advisory Board recently proposed the development of the ICIQ website, which is anticipated to be crucial for informing potential users of the phase of development of all ICIQ modules. CONCLUSION: The ICIQ can offer a full range of urinary tract symptom questionnaires. The website will aim to attract collaborators committed to the concept of this internationally accepted modular questionnaire who are willing to help with its development.

Internationality↗

PubMed1995

Project 2000: a modular approach to course planning.

Project 2000 has given nurse educators an opportunity to consider and plan educational programmes that will endure until the year 2000 and beyond. The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (1986) highlighted the need for preparing practitioners for uncertainty by developing structures that adapt to rapid change. This includes planning smaller units of study, that are accessible and allow for credit transfers. This article describes the development of a semester based, modular programme of study, for Project 2000. The idea of modularity, both from the higher education and nurse education perspective is examined. An outline of the course is offered and for the benefit of colleagues who may be considering embarking on a similar remit, areas of difficulty encountered on implementation are highlighted with some resolutions.

Curriculum↗

PubMed2002

Trout GH promoter analysis reveals a modular pattern of regulation consistent with the diversification of GH gene control and function in vertebrates.

In vertebrates, growth hormone (GH) gene expression requires the pituitary-specific transcription factor Pit-1/GHF1 but is differently regulated by a variety of factors in different vertebrate species. Here, we have studied the transcriptional activity of the trout GH (tGH) promoter, which is synergistically stimulated by cAMP and glucocorticoid. Gel shift assays indicated that Pit-1 binds as a dimer to three high affinity sites in the -226/+24 tGH region, and that recombinant cAMP response element (CRE)-binding protein (CREB) binds to a CRE situated between the two distal Pit-1 sites. Deletional and mutational transfection experiments, performed in pituitary Pit-1-expressing GC cells, showed that the different Pit-1 sites play distinct roles and are obligatory elements in the mechanisms mediating cAMP and glucocorticoid responses. Remarkably, the results suggest a hierarchical modular model of regulation of the tGH promoter, according to which a critical module, triggered by Pit-1 bound to the proximal Pit-1 site, is necessary and sufficient to turn on and drive basal levels of transcription. The latter may be stimulated synergistically by two Pit-1-dependent reciprocally non-cooperative auxiliary modules, activated by cAMP and glucocorticoid, respectively. Such modularity explains, in evolutionary terms, the crucial role played by Pit-1 in transcriptional activation and the emergence of the wide variety of mechanisms regulating transcriptional levels of GH, prolactin and other Pit-1-target genes in vertebrates.

Animals↗