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Motor maps and synergies.

Consider the process of raising and lowering the arm in the sagittal plane. Different parts of different muscles operate over different sectors of the angular range. How and why does the nervous system implement this differential muscle activation according to joint angle? We contend that such control depends on the adaptive formation of motor maps. These solve the problem of redundancy in the musculoskeletal system by connecting a relatively small number of cortical columns in the motor cortex to a large number of alpha motor neuron pools. We argue that motor maps are formed such that each functional muscle is activated in proportion to its moment arm about the movement. Because of this the required agonist and antagonist turning forces are generated with a minimum demand for metabolic energy. We know from biomechanical principles that, at any given posture, those muscle fibres that change length most in response to a small joint-angle change are those with the greatest moment arm. Likewise those that change least have the smallest. By establishing a model of the polynomial relationships between the lengths of functional muscles l and the corresponding changes in joint angles theta, the nervous system can generate signals partial differentiallj/ partial differentialthetai (where lj is the length of the jth functional muscle and thetai is the magnitude of the ith elemental movement). These signals create motor maps by modulating the gains of descending motor pathways. As a result, functional muscles are activated in proportion to their moment arms. This reduces the demand for metabolic energy to a minimum. Since moment arms change with joint angle, it also accounts for the experimental observations above. Such motor mapping effectively provides a minimum energy "wired-in" synergy. Established in utero, motor maps are the first stage of synergy formation and provide the basis for the development of subsequent task-dependent synergies.

Biomechanical Phenomena↗

The yeast MATa1 gene contains two introns.

In the yeast Saccharomyces cerevisiae there are two mating types, a and alpha, which may mate to produce an a/alpha diploid. Mating type is determined by the allele (MATa or MAT alpha) occupying the MAT locus. In a diploid, expression of the MATa1 and MAT alpha 2 genes determines the a/alpha state by regulating the expression of unlinked genes. Previous S1 endonuclease mapping implied that the MATa1 transcript is not processed. We have performed further S1 mapping of this transcript, demonstrating that the MATa1 gene contains two introns, unlike any other characterized nuclear gene in yeast. Both introns contain 5' splice sites and 5'- TACTAACA -3' consensus sequences at the positions predicted by the S1 mapping data. In the splicing-defective rna2 mutant, the mature message disappears rapidly and the precursor RNA accumulates. The RNA processing removes the UGA stop codon which was previously believed to be read-through.

Base Sequence↗

MAP kinases in the immune response.

MAP kinases are among the most ancient signal transduction pathways and are widely used throughout evolution in many physiological processes. In mammalian species, MAP kinases are involved in all aspects of immune responses, from the initiation phase of innate immunity, to activation of adaptive immunity, and to cell death when immune function is complete. In this review, we summarize recent progress in understanding the function and regulation of MAP kinase pathways in these phases of immune responses.

Animals↗

[Comparison of body surface maps with epicardial maps in patients with Wolff-Parkinson-White syndrome].

To investigate the ventricular activation process reflected on body surface maps, we compared body surface isopotential and isochrone maps with epicardial isochrone maps in 39 patients with Wolff-Parkinson-White syndrome. The epicardial earliest activation site, the latest activation site and the distribution of isochrone line during mid QRS period were reflected well on the location of minimum during early QRS period, the location of maximum during terminal QRS period, and the movement of base line during mid QRS period on isopotential maps respectively. Right ventricular breakthrough via normal conduction pathway was recognized on epicardial maps in most patients with left sided or septal accessory pathway, though some patients had it on isopotential maps and a few patients had it on isochrone maps. The unique distribution of initial minimum in patients with posteroseptal pathway was caused by the ventricular fusion of the preexcitation at diaphragmatic base and the normal activation at right ventricular free wall.

Adult↗

Common prefrontal regions coactivate with dissociable posterior regions during controlled semantic and phonological tasks.

One of the most ubiquitous findings in functional neuroimaging research is activation of left inferior prefrontal cortex (LIPC) during tasks requiring controlled semantic retrieval. Here we show that LIPC participates in the controlled retrieval of nonsemantic representations as well as semantic representations. Results also demonstrate that LIPC coactivates with dissociable posterior regions depending on the information retrieved: activating with left temporal cortex during the controlled retrieval of semantics and with left posterior frontal and parietal cortex during the controlled retrieval of phonology. Correlation of performance to LIPC activation suggests a processing role associated with mapping relatively ambiguous stimulus-to-representation relationships during both semantic and phonological tasks. These findings suggest that LIPC participates in controlled processing across multiple information domains collaborating with dissociable posterior regions depending upon the kind of information retrieved.

Adult↗

Effects of dopamine, NMDA, opiate, and serotonin-related agents on acute methamphetamine-induced self-injurious behavior in mice.

We examined the biochemical processes responsible for acute methamphetamine (MAP)-induced self-injurious behavior (SIB) in mice. In initial experiments, a single dose of MAP (5, 10, or 15 mg/kg, IP) or an equivalent volume of saline was administered to male BALB/c mice. Acute MAP administration dose dependently increased the incidence of SIB (p < 0.05). In further experiments, we evaluated the effects of SCH23390, sulpiride, MK-801, naloxone or 5-hydroxy-L-tryptophan (5-HTP) on the incidence of acute MAP (15 mg/kg, IP)-induced SIB. Both SCH23390 (0.5 and 1.0 mg/kg, IP) and 5-HTP (100 and 200 mg/kg, IP) reduced the incidence of MAP-induced SIB (p < 0.05). MK-801 (0.125 and 0.25 mg/kg, IP) completely blocked the SIB induced by MAP (p < 0.001). In contrast, neither sulpiride (25, 50, and 100 mg/kg, IP) nor naloxone (1, 5, and 10 mg/kg, IP) affected the incidence of MAP-induced SIB. It is concluded that dopamine D(1), NMDA, and serotonin neurotransmission may be involved in critical biochemical processes responsible for acute MAP-induced SIB.

5-Hydroxytryptophan↗

A statistical model for functional mapping of quantitative trait loci regulating drug response.

Differential drug response, that is, pharmacodynamics, is most often likely to be a complex trait, controlled by the combined influences of multiple genes and environmental influences. Genetic mapping has proven to be a powerful tool for detecting and identifying specific genes affecting complex traits, that is, quantitative trait loci (QTL), based on polymorphic markers. In this article, we present a novel statistical model for genetic mapping of QTL governing pharmacodynamic processes. In principle, this model is a combination of functional mapping proposed to map function-valued traits and linkage disequilibrium mapping designed to provide high-resolution mapping of QTL by making use of recombination events created at a historic time. We implement a closed-form solution for the Expectation-Maximization algorithm to estimate the population genetic parameters of QTL and the simplex algorithm to estimate the curve parameters describing the pharmacodynamic changes of different QTL genotypes in response to drug dose or concentrations. Extensive simulations are performed to investigate the statistical properties of our model. The implications of our model in pharmacogenetic and pharmacogenomic research are discussed.

Algorithms↗

Insulin increases the processing efficiency of messenger ribonucleic acid-S14 nuclear precursor.

Feeding a lipogenic diet increases transcription and enhances processing of the rat hepatic messenger RNA (mRNA)-S14 gene. To determine the separate roles of insulin and increased glucose in these processes, we used the streptozotocin-induced diabetic rat model. Diabetes caused a reduction in mature mRNA-S14 in chow- and lipogenic diet-fed animals (P < 0.006 and P < 0.001, respectively). Insulin restored these levels to normal. Despite the known effects of insulin and carbohydrate on the transcription of this gene, we were unable to demonstrate significant changes in the nuclear proteins that bind to carbohydrate response regions. Yet, insulin restored the content of the mRNA by increasing the ratio of mature to precursor mRNA-S14. Insulin significantly increased this ratio (P < 0.0001) independent of diet and diabetes, further supporting the action of insulin on increasing processing from precursor to mature mRNA. The mechanism of the enhanced processing was studied by ribonuclease mapping and primer extension analysis. Ribonuclease mapping showed that lipogenic diet feeding increases the efficiency of processing at a step before formation of the branched form of the precursor mRNA. Taken together, our data demonstrate for the first time that insulin significantly enhances the efficiency of processing of a pre-mRNA.

Animals↗

Modeling 3-D compliant blood flow with FOSLS.

Blood flow in large vessels is typically modeled using the Navier-Stokes equations for the fluid domain and elasticity equations for the vessel wall. As the wall deforms, additional complications are introduced because the shape of the fluid domain changes, necessitating the use of a re-mapping or re-griding process for the fluid region. Typically, this system (fluid, solid, mapping) is solved using an iterative approach in which the fluid, elastic, and mapping equations are solved in series until the iterations converge. We present a new approach based on multilevel minimization of the finite element approximation error using a least-squares (LS) norm. This approach allows for minimization of the error for the entire system or in selected parts. The multilevel LS approach overcomes many shortcomings of standard techniques. Most notably, the computational cost of solving the problem increases linearly with the degrees of freedom and the associated least-squares functional provides an a posteriori error measure. This paper compares the LS finite element approach to other popular numerical methods, specifically, the commercial package CFD-ACE. The focus of the comparison is on accuracy, computational cost, scalability (both parallel and serial), and flexibility. We show that the multilevel LS finite element approach scales optimally (i.e., linearly in serial environments), while the other methods degrade substantially as the problem size increases.

Algorithms↗

Microstates in language-related brain potential maps show noun-verb differences.

Brain processing of grammatical word class was studied analyzing event-related potential (ERP) brain fields. Normal subjects observed a randomized sequence of single German nouns and verbs on a computer screen, while 20-channel ERP field map series were recorded separately for both word classes. Spatial microstate analysis was applied, based on the observation that series of ERP maps consist of epochs of quasi-stable map landscapes and based on the rationale that different map landscapes must have been generated by different neural generators and thus suggest different brain functions. Space-oriented segmentation of the mean map series identified nine successive, different functional microstates, i.e., steps of brain information processing characterized by quasi-stable map landscapes. In the microstate from 116 to 172 msec, noun-related maps differed significantly from verb-related maps along the left-right axis. The results indicate that different neural populations represent different grammatical word classes in language processing, in agreement with clinical observations. This word class differentiation as revealed by the spatial-temporal organization of neural activity occurred at a time after word input compatible with speed of reading.

Adult↗

Using intervention mapping to develop a breast and cervical cancer screening program for Hispanic farmworkers: Cultivando La Salud.

This article describes the development of the Cultivando La Salud program, an intervention to increase breast and cervical cancer screening for Hispanic farmworker women. Processes and findings of intervention mapping (IM), a planning process for development of theory and evidence-informed program are discussed. The six IM steps are presented: needs assessment, preparation of planning matrices, election of theoretic methods and practical strategies, program design, implementation planning, and evaluation. The article also describes how qualitative and quantitative findings informed intervention development. IM helped ensure that theory and evidence guided (a) the identification of behavioral and environmental factors related to a target health problem and (b) the selection of the most appropriate methods and strategies to address the identified determinants. IM also guided the development of program materials and implementation by lay health workers. Also reported are findings of the pilot study and effectiveness trial.

Adolescent↗

Controlled struvite crystallisation for removing phosphorus from anaerobic digester sidestreams.

Enhanced biological phosphorus removal wastewater treatment plants that use anaerobic digesters for sludge treatment, have high phosphorus concentrations in the sidestreams from their sludge dewatering equipment. To remove phosphorus from such sidestreams controlled struvite crystallisation can be used. Struvite (or MAP) is a naturally occurring crystal of magnesium, ammonium and phosphate. We present operational results obtained with a continuously operated pilot-scale MAP reactor. The pilot-scale reactor (143 l) was an air agitated column reactor with a reaction and a settling zone, based on the Phosnix process of Unitika Ltd., Japan. The influent to the MAP reactor was centrate from the centrifuge that dewaters anaerobically digested sludge at the Oxley Creek wastewater treatment plant in Brisbane. We used a 60% magnesium hydroxide slurry to add the required magnesium to the process and to obtain the alkaline pH value required. The pilot-scale MAP process achieved an ortho-P removal ratio of 94% from an average influent ortho-P concentration of 61 mg/l. The reactor was operated at a pH of around 8.5. Insufficient dosing of magnesium reduced the P removal performance. There was no influence of the hydraulic residence time on the process in the range of 1-8 h. The dry MAP product had cadmium, lead and mercury concentrations well below the legal limits for fertilisers in Queensland, Australia and can be reused as a valuable slow-release fertiliser.

Ammonia↗

Registration of medical images using an interpolated closest point transform: method and validation.

Image registration is an important procedure for medical diagnosis. Since the large inter-site retrospective validation study led by Fitzpatrick at Vanderbilt University, voxel-based methods and more specifically mutual information-based registration methods (see for instance [IEEE Trans. Med. Imag. 22 (8) (2003) 986] for a review on these methods) have been regarded as the method of choice for rigid-body intra-subject registration problems. In this study we propose a method that is based on the Iterative Closest Point algorithm and a pre-computed closest point map obtained with a slight modification of the fast marching method proposed by Sethian. Pre-computing the closest point map speeds up the process because at each iteration point correspondence can be established by table lookup. We also show that because the closest point map is defined on a regular grid it introduces a registration error and we propose an interpolation scheme that addresses this issue. The method has been tested both on synthetic and real images, and registration results have been assessed quantitatively using the data set provided by the Retrospective Registration Evaluation Project. For these volumes, MR and CT head surfaces were extracted automatically using a level-set technique. Results show that on these data sets this registration method leads to accuracy numbers that are comparable to those obtained with voxel-based methods.

Algorithms↗

Epitope-targeted proteome analysis: towards a large-scale automated protein-protein-interaction mapping utilizing synthetic peptide arrays.

We describe the development of a process for the genome-wide mapping of interactions between protein domains and peptide ligands entirely based on high-throughput biochip technologies. A phage library displaying protein domains from a randomly fragmented and cloned cDNA library will be "panned" on an array of synthetic peptide ligands. After multiplexed affinity enrichment, peptide-specific phage populations will be automatically eluted, propagated, labelled and identified by hybridisation to a DNA microarray. Peptide arrays are synthesized in situ by SPOT synthesis on a planar substrate. By utilizing a commercially available library of human brain cDNA plus a set of distinct model domains cloned into T7-phage, we could show that a single panning round on an array of known peptide ligands for these model domains synthesized on a cellulose membrane can yield an enrichment of better than a factor of 1,000. This is sufficient to detect peptide-specific enrichment of Cy3(post-panning) against Cy5(pre-panning)-labelled phage DNA inserts on a cDNA microarray. Thus, the proof-of-principle of our approach could be successfully demonstrated and first interaction data are being collected.

Amino Acid Sequence↗

Light-response quantitative trait loci identified with composite interval and eXtreme array mapping in Arabidopsis thaliana.

Genetic analysis of natural variation in ecotypes of Arabidopsis thaliana can facilitate the discovery of new genes or of allelic variants of previously identified genes controlling physiological processes in plants. We mapped quantitative trait loci (QTL) for light response in recombinant inbred lines (RILs) derived from the Columbia and Kashmir accessions via two methods: composite interval mapping and eXtreme array mapping (XAM). After measuring seedling hypocotyl lengths in blue, red, far-red, and white light, and in darkness, eight QTL were identified by composite interval mapping and five localized near photoreceptor loci. Two QTL in blue light were associated with CRY1 and CRY2, two in red light were near PHYB and PHYC, and one in far-red light localized near PHYA. The RED2 and RED5 QTL were verified in segregating lines. XAM was tested for the identification of QTL in red light with pools of RILs selected for extreme phenotypes. Thousands of single feature polymorphisms detected by differential DNA hybridized to high-density oligo-nucleotide arrays were used to estimate allele frequency differences between the pools. The RED2 QTL was identified clearly; differences exceeded a threshold of significance determined by simulations. The sensitivities of XAM to population type and size and genetic models were also determined by simulation analysis.

Arabidopsis↗

How a three-campus heart service line improves clinical processes and outcomes.

BACKGROUND: In 1993, Intermountain Health Care's three Salt Lake Valley Hospitals formed service lines in four clinical areas, one of which was heart services. After experimenting with various organizational structures, the Salt Lake Valley Hospitals formed a cardiac executive council and three specialty work teams--the clinical process and outcome, satisfaction, and resource teams--to allow for unified planning and greater teamwork. CASE STUDY--OPEN HEART TEAM: The team mapped out the current process and identified areas for potential improvement in the care of patients undergoing coronary artery bypass graft (CABG) surgery. One of the key processes selected for study was extubation. Patients were extubated for an average of 20.41 hours (range, 6 to 120 hours). Analysis of practice patterns demonstrated that extubation was related to staffing patterns, not the patient's readiness. The team created a weaning path, which reduced extubation time to an average of 8.89 hours. LESSONS LEARNED: A common vision and an organized structure to support integrated services is essential. Cross-training of staff helps ensure that the same standards of care apply across the three campuses. Even when the medical staff and hospital departments each have their own structures for dealing with quality issues, cohesiveness among physicians treating a certain group of patients, such as cardiac patients, can be promoted. In conclusion, a "cardiac culture" that is evident throughout the three hospitals promotes performance improvement.

Angioplasty, Balloon, Coronary↗

Probabilistic annotation of protein sequences based on functional classifications.

BACKGROUND: One of the most evident achievements of bioinformatics is the development of methods that transfer biological knowledge from characterised proteins to uncharacterised sequences. This mode of protein function assignment is mostly based on the detection of sequence similarity and the premise that functional properties are conserved during evolution. Most automatic approaches developed to date rely on the identification of clusters of homologous proteins and the mapping of new proteins onto these clusters, which are expected to share functional characteristics. RESULTS: Here, we inverse the logic of this process, by considering the mapping of sequences directly to a functional classification instead of mapping functions to a sequence clustering. In this mode, the starting point is a database of labelled proteins according to a functional classification scheme, and the subsequent use of sequence similarity allows defining the membership of new proteins to these functional classes. In this framework, we define the Correspondence Indicators as measures of relationship between sequence and function and further formulate two Bayesian approaches to estimate the probability for a sequence of unknown function to belong to a functional class. This approach allows the parametrisation of different sequence search strategies and provides a direct measure of annotation error rates. We validate this approach with a database of enzymes labelled by their corresponding four-digit EC numbers and analyse specific cases. CONCLUSION: The performance of this method is significantly higher than the simple strategy consisting in transferring the annotation from the highest scoring BLAST match and is expected to find applications in automated functional annotation pipelines.

Algorithms↗

Locating the motor cortex on the MRI with transcranial magnetic stimulation and PET.

Transcranial magnetic stimulation with a focal coil was used to map the cortical representation of a hand muscle in four healthy subjects. In each subject, the three-dimensional locations of the magnetic stimulation positions and about 400 positions on the surface of the head were digitized. The amplitude-weighted center of gravity of each subject's map was found, and a line perpendicular to the local head surface was projected inward. The digitized heads were registered with the subjects' MRIs using the scalp contours. The coordinate transformations yielded by this process were used to map the stimulation positions and the perpendicular line into the MRIs. Brain areas imaged with positron emission tomography (PET) and 15O-labeled water, activated by movement of the same muscle, were registered with the MRIs using the brain contours. In all cases, the magnetic stimulation lines encountered the surface of the brain at the anterior lip of the central sulcus and ran along the precentral gyrus a few millimeters anterior to the central sulcus, coming within 5-22 mm of all the PET activation maxima. This technique demonstrates the accuracy of transcranial magnetic stimulation for locating the primary motor area.

Adult↗