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Dipole source localization in the study of EP generators: a critique.

(1) The decision to solve the inverse problem in terms of one or more localized generators implies the assumption of a particular generator model. This assumption permits carrying out inverse dipole estimation. However, it is perilous to justify the procedure on the basis of the result. (2) Goodness of fit is a necessary but not sufficient criterion of model adequacy. A particular quantitative inverse solution has meaning only if it is accompanied by consideration of sensitivity to small changes in all of the free modeling parameters and estimates of perturbing factors including noise and forward calculation uncertainties.

Brain Mapping↗

Frequency analysis of amino acids in the recognition regions of T-cell receptors.

In immunoglobulins (Igs), key amino acids in the Complementarity Determining Regions (CDR) are responsible for maintaining specific conformations called canonical structures. In T-cell receptors (TCRs), protein members of the Ig superfamily, the corresponding residues for maintaining these canonical structures have not been found. In previous studies we have found in Igs that the frequency of use of amino acids in some positions of the CDRs follows an inverse power law distribution, while the frequency of amino acids in the rest of the positions of the CDRs follows an exponential law distribution. The positions that follow the inverse power law distribution are precisely those involved in maintaining the canonical structures, while those positions for which the distribution fits the exponential distribution are those that should be properly involved in the recognition mechanism. In this paper, when the same analysis is applied to the use frequency of amino acids on the CDRs of TCRs, it is found that some positions that have been previously identified as having a structural role are those fitting the inverse power law. That finding combined with the cooperative or long-range interaction properties of systems that follow the inverse power law leads us to propose that the lack of determined key residues in certain positions is compensated by "equivalent' residues in other positions within the CDRs in order to maintain the canonical structures. Other positions that follow the exponential distribution are those which can be involved in the recognition process. These results coincide with a computer-generated model of TCR/peptide/MHC interaction previously published by the authors.

Amino Acid Sequence↗

Temporary and permanent migration with and without an immobile factor.

"This paper develops two two-country overlapping-generations models--one with and one without an immobile factor--to study temporary and permanent migration. Temporary migration is shown to be equivalent to international lending and borrowing. One strong result found in the literature that if natives of each country are homogenous permanent migration leads to the migration of the entire population of the [sending] country in the long run is overturned. Welfare effects of migration are analyzed."

Demography↗

Nucleotide sequence of the argF regulatory region of Escherichia coli K-12.

The deoxyribonucleotide sequence has been determined for the regulatory region of the arginine F gene (argF) of Escherichia coli K-12. The location of the argF coding region was deduced by comparison of the DNA sequence to the sequence predicted from the primary structure of the N-terminus of the argF gene product, the subunit of the "F" isoenzyme of ornithine transcarbamylase. Transcription of the argF gene was found to initiate at a position approx. 40 bp preceding the N-terminal codon for OTCase. Comparison of the region surrounding the origin of transcription with a computer-generated "model promoter sequence" revealed structural similarities between the two sequences, in particular, the promoter-associated stretches known as the "Pribnow box" and "minus 35 contact site". Another feature noted for the argF promoter region was its extreme abundance of A : T nucleotide pairs. In the region preceding the start site for argF translation, a sequence was observed to be complementary to the 3' end of the 16S RNA component of the E. coli ribosome. Both the length and the nucleotide sequence of the argF leader region indicate that the argF gene does not contain an attenuator proposed to exist in other operons concerned with amino acid biosynthesis.

Bacterial Proteins↗

Gadolinium-DTPA-enhanced and digitally subtracted magnetic resonance imaging of estrogen-induced pituitary lesions in rats: correlation with pituitary anatomy.

Pituitary hypertrophy and tumors were induced in male Sprague Dawley rats using estradiol-17 beta. This tumor model generates a variety of pituitary lesions which are relevant to human pituitary disease. In order to characterize these lesions, gadolinium DTPA was injected intravenously into the tail vein of estrogen treated and control rats. High resolution T1-weighted MR images, pre- and postenhancement, were obtained at 8 different time points spanning 300 days following the subcutaneous implantation of the estrogen pellets. Images with 2-mm slice thickness were made with a 2 Telsa small-bore MR imaging system. Both normal and tumorous pituitaries were found to enhance with contrast agent, but contrast uptake was not uniform. Gd-DTPA distribution was sensitive to the different types of lesions generated in the course of this study. Digital subtraction of congruent images, pre- and postcontrast, provided difference images reflecting contrast concentration and allowed identification of subtle enhancement effects. Hypertrophic pituitaries displayed uptake of contrast, but the distribution of contrast agent was nonuniform and appeared mottled. A bright rim enhancement was often seen anterior to the pituitary gland, most likely arising from the oculomotor nerves and arachnoid. Histological slices in the same anatomical plane as the MR images were obtained on the animals allowing identification of individual lesions. Cystic areas within tumors were found to give strong contrast enhancement in less than five min postinjection. Solid and hemorrhagic areas of the pituitary tumor were hypo- to isointense relative to surrounding brain and did not take up contrast agent. Significant perfusion in these areas apparently does not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of pharmacological interventions in the prevention of lipid peroxidation and respiratory depression induced by oxygen free radicals in anesthetized rats.

We have recently reported that in an anesthetized rat model, generation of oxygen free radicals (OFR) via i.v. administration of Xanthine plus Xanthine Oxidase [X + XO] resulted in death of about 90% of the animals within a 120-min observation period. Pretreatment of the rats with endogenous scavengers Superoxide Dismutase and Catalase, or with felodipine, a dihydropyridine calcium channel blocker, and/or with dopexamine, an agonist of beta 2 adrenoceptors as well as dopamine (DA-1) receptors significantly enhanced the survival rate to over 70%. The present study was designed to investigate whether lipid peroxidation and ensuing respiratory depression contributed to the lethal toxicity of the free radicals. In the control group, the death of the rats administered [X + XO] was proceeded by significant increases in the plasma lipid peroxides (PLP) and by a severe hypertensive response characteristic of an intense ischemic state, which was confirmed by the presence of hypercapnia, hypoxemia, and acidosis. Placement of the animals on the positive pressure ventilation prior to the administration of [X + XO] did not prevent increases in PLP but, prevented any adverse alterations in the respiratory markers and significantly enhanced survival rate up to 70%. In contrast, both felodipine as well as dopexamine prevented any increases in PLP, normalized blood gas profile, and significantly increased survival rate to 80 to 90%. These observations suggest that the lethal toxicity produced by oxygen free radical was due to respiratory distress. The relationship between increases in the PLP and respiratory depression and the mechanisms via which two pharmacologically distinct agents, felodipine and dopexamine, facilitated the salutary effects cannot be conclusively stated at this time. It is further suggested that although the doses of these two drugs employed in the present studies are not adequate to function as antioxidants, such a possibility cannot be entirely ruled out.

Anesthesia↗

Model control of image processing: pupillometry.

Smart instruments require on-line computers, special purpose hardware, or both. A pupillometer is described that relies only on a general purpose microcomputer with a frame grabber to process infrared video camera pictures of the human eye. An essential feature of the instrument is that a top-down model controls the image processing algorithms. The model generates regions of interest, ROIs, positioned from knowledge of anatomy and optics of the eye and information from previously analyzed frames. Within these adaptively controlled ROIs, fast, run-time algorithms automatically calculate local thresholds, area measurements, moments for centroid position information, and use pyramiding to shorten calculation time for large pupils. Outputs are precise measurements of pupil size and eye position in real time, with adequate bandwidth for most purposes.

Artificial Intelligence↗

Prediction of employability in schizophrenic patients.

This study, the third of a series of reports on employability and schizophrenia, investigated the effects of both interview and non-interview variables on employability. Data on 46 chronic schizophrenic inpatients included demographic and illness-related variables, measures of psychopathology and interview-based ratings of employment skill. Latent class analysis using linear structural relations (LISREL) modelling generated the main finding namely, that interview-based measures are the strongest determinants of employability. However, other variables pertaining to illness, prior functioning and negative symptoms, exert an effect on interview performance and hence indirectly influence employability ratings and judgements.

Activities of Daily Living↗

Cell proliferation patterns in the wing imaginal disc of Drosophila.

Morphogenetic processes, based on the temporal and spatial control of cell proliferation, are involved in determining the size and shape of an organism. We have used clonal analysis, employing X-ray-induced mitotic recombination, to study cell proliferation and differentiation processes in the developing wing imaginal disc of Drosophila. Our results show a non-uniform distribution of mitotic activities during different stages of wing development. This may reflect waves of cell proliferation which derive from distinct centers of cell proliferation within the growing wing imaginal disc. These proliferation centers are located within the major wing compartments (i.e. the anterior, posterior, dorsal and ventral compartments) and they are restricted to the areas which give rise to the intervein regions of the adult wing. The mitotic recombination analysis, combined with the study of Minute and gynandromorph mosaics, show that the presumptive vein regions of the wing represent distinct boundaries which delimit the proliferation centers to the intervein regions. We present a generative model of wing morphogenesis that is consistent with our results.

Animals↗

Can stock rotation effectively mitigate EMS medication exposure to excessive heat and cold?

The United States Pharmacopeia recently published a general chapter specifically addressing on-ambulance storage of medications, including a suggestion for stock rotation. This study describes the effectiveness of a simple stock rotation strategy in mitigating EMS medication exposure to excessive heat and cold. Previously collected on-ambulance temperature data from 5 US cities were randomly resampled to generate model exposures of 2 days to 6 months duration. The temperature measurements for every other 24-hour period were then set at 20 degrees C to model the rotation of medications into a controlled environment. For each model, we then determined consistency with the official United States Pharmacopeia definition of controlled room temperature. Without stock rotation, excessive heat occurred in 39.9% of the model exposures. With stock rotation, exposures to excessive heat occurred in less than 1% of northern city models and in 2.9% of the central US models. Stock rotation did not reduce heat exposures in the models for southern cities.

Ambulances↗

Alaryngeal speech aid using an intra-oral electrolarynx and a miniature fingertip switch.

We developed and evaluated an intra-oral electrolaryngeal speech aid system for those who could not acquire common alaryngeal speech or for early post-surgery speech rehabilitation. Our system consisted of a denture-base intra-oral vibrator, a wireless miniature fingertip switch and a controller. To produce natural speech, the fingertip switch produced binary commands of voicing and accent and the controller implemented the pitch generation model using the commands. We first estimated the intelligibility of consonant-vowel syllables produced by our system. We then obtained the feedback about the system from the Japanese users on the basis of their daily life use, and evaluated the possibility and acceptability as an alaryngeal speech aid. Although the users were less satisfied at the intra-oral electrolarynx, the intelligibility of the intra-oral electrolarygeal speech was comparable to that of transcervical electrolaryngeal speech, and most of them were willing to employ it if they lost their current electrolaryngeal speech. According to the feedbacks from the users, a completely wire-free system and less eye-catching designs would make the prosthesis more acceptable. These results placed the intra-oral electrolarynx as a useful option of alaryngeal speech aids and encouraged the further development of the intra-oral electrolarynx.

Aged↗

Generalised and conditional inactivation of Pex genes in mice.

During the past 10 years, several Pex genes have been knocked out in the mouse with the purpose to generate models to study the pathogenesis of peroxisome biogenesis disorders and/or to investigate the physiological importance of the Pex proteins. More recently, mice with selective inactivation of a Pex gene in particular cell types were created. The metabolic abnormalities in peroxisome deficient mice paralleled to a large extent those of Zellweger patients. Several but not all of the clinical and histological features reported in patients also occurred in peroxisome deficient mice as for example hypotonia, cortical and cerebellar malformations, endochondral ossification defects, hepatomegaly, liver fibrosis and ultrastructural abnormalities of mitochondria in hepatocytes. Although the molecular origins of the observed pathologies have not yet been resolved, several new insights on the importance of peroxisomes in different tissues have emerged.

Animals↗

Preferential loss of 5S and 28S rDNA genes in human adipose tissue during ageing.

Loss of genomic rDNA has been associated with cellular and organismal ageing. The rDNA locus in humans comprises multiple copies of the 5.8S, 28S and 18S genes. Aim of the present study was to test the effect of aging on the copy number of the three rDNA genes individually in post-mitotic human tissue. We utilized real time polymerase chain reaction relative quantification to measure the copy number of 5.8S, 28S and 18S rDNA genes individually. We obtained adipose tissue from 120 male individuals aged from 9 to 94 years. The available data of each subject corresponding to the time of tissue sampling included: age, height, weight and calculated body mass index. Each rDNA gene was directly tested with Pearson correlation against age and body mass index. We found a significant negative correlation of the gene copy of 5.8S (P < 0.001) and 28S (P < 0.003) with age. Interestingly 18S gene copy displayed a different pattern with no statistically significant correlation with age. Conversely, we observed a significant negative correlation of the 18S gene copy with body mass index (P = 0.004) and a marginally non-significant negative correlation of the 5.8S (P = 0.097) gene copy with body mass index. In summary our results indicate that the rDNA recombination events in humans can be differentially targeted and regulated in response to ageing and/or fat accumulation. The proposed model generates possible implications regarding the effects of each rDNA gene loss in cell function as well as the mechanism of recombination targeting.

Adipose Tissue↗

Estimation of maturity of compost from food wastes and agro-residues by multiple regression analysis.

The composting process of food wastes and tree cuttings was examined on four composting types composed from two kinds of systems and added mixture of microorganisms. The time courses of 32 parameters in each composting type were observed. The efficient composting system was found to be the static aerated reactor system in comparison with the turning pile one. Using the multiple regression analysis of all the data (159 samples) obtained from this study, some parameters were selected to predict the germination index (GI) value, which was adopted as a marker of compost maturity. For example, using the regression model generated from pH, NH(4)(+) concentration, acid phosphatase activity, and esterase activity of water extracts of the compost, GI value was expressed by the multi-linear regression equation (p<0.0001). High correlations between the measured GI value and the predicted one were made in each type of compost. As a result of these observations, the compost maturity might be predicted by only sensing of the water extract at the composting site without any requirements for a large-size equipment and skill, and this prediction system could contribute to the production of a stable compost in wide-spread use for the recycling market.

Acid Phosphatase↗

Volumetric spatial decomposition of trabecular bone into rods and plates--a new method for local bone morphometry.

Bone microarchitecture is believed to play a key role in determining bone quality. We therefore present a new method for the volumetric spatial decomposition of trabecular bone samples into its basic elements (rods and plates). This new method is a framework for the element based description of bone microarchitecture. First, the newly developed algorithm was validated on computer-generated models. Then, it was applied to 328 human trabecular bone samples harvested from 70 donors at five different anatomical sites (calcaneus, femoral head, iliac crest, lumbar spine 2 and 4), which were previously scanned by microcomputed tomography. Standard three-dimensional morphometric algorithms were used to analyze the trabeculae on an individual basis with respect to their volume, surface, and thickness. The results were statistically compared for the five sites. In this study, it was possible for the first time to spatially decompose trabecular bone structures in its volumetric elements; rods and plates. The size of the largest element in the structures showed significant differences for the five compared sites. In samples from femoral head, we found that basically one "major element" was spanning through the whole structure whereas in lumbar spine and calcaneus, smaller elements dominate. From this, we suggest that the strength of strong, dense plate-like structures is determined by the major elements whereas in looser rod-like structures the strength is given by the arrangement, quality, and shape of a whole set of elements. Furthermore, we found that globally determined structural indices such as the mean curvature of the bone surface ( ) or related to this the structure model index (SMI) are almost exclusively explained by the arrangement of the plates. This also suggests that rods hold independent information characterizing trabecular bone quality, especially in the spine. These findings may improve the understanding of the site-specific role of bone microarchitecture in determining bone quality and in future studies the competence of bone.

Adult↗

Dynamics of chromosome positioning during the cell cycle.

The arrangement and dynamics of chromosomes inside the nucleus of mammalian cells have been studied intensively over the last two years. Although chromosomes are relatively immobile and occupy non-random positions in interphase, their dynamic movements in mitosis have traditionally been assumed to randomize this arrangement. New methods of live cell imaging now make it possible to follow chromosome movements directly and quantitatively in single cells. Such studies have generated models of chromosome positioning throughout the cell cycle and provide a new basis to address the underlying mechanisms in future experiments.

Animals↗

A prospective randomized trial comparing the 1-stage with the 2-stage implantation of a pulse generator in patients with pelvic floor dysfunction selected for sacral nerve stimulation.

OBJECTIVE: The aim of this study was to evaluate in a prospective, randomized setting if the 2-stage implant, compared to a 1-stage implant, leads to a superior subjective or objective outcome of sacral nerve stimulation after implantation of the pulse generator in patients with lower urinary tract symptoms. PATIENTS AND METHODS: We implanted a sacral (S3) foramen lead and a pulse generator (model 3023, Medtronic Inc, Minneapolis, MN, USA) in 42 patients. They were randomized in a 1-stage or a 2-stage implant if a more than 50% improvement in voided volume or reduction of residual urine was seen during the test stimulation phase as compared to baseline. RESULTS: At 24 months follow-up, subjective (visual analogue scale) and objective (voided volume or residual urine) assessment were significantly better in the 2-stage group. Ten patients (24%) failed therapy, 7 in the 1-stage implant and 3 in the 2-stage group. Two patients were lost to follow-up. Logistic regression analysis revealed that failure was positively related to the 1-stage implant and negatively to the age of the patients. 76% of the treated patients had sustained clinical benefit with 23 revisions performed. The mean cost is respectively for the PNE (2006 Euro), for the 2-stage implant (10826 Euro) and for the 1 stage implant (8505 Euro). CONCLUSION: With this study, we demonstrated that the 2-stage implantation technique of the sacral neuromodulation therapy performed as a longer test stimulation phase has a higher success rate.

Algorithms↗

Membrane topology of human ABC proteins.

In this review, we summarize the currently available information on the membrane topology of some key members of the human ABC protein subfamilies, and present the predicted domain arrangements. In the lack of high-resolution structures for eukaryotic ABC transporters this topology is based only on prediction algorithms and biochemical data for the location of various segments of the polypeptide chain, relative to the membrane. We suggest that topology models generated by the available prediction methods should only be used as guidelines to provide a basis of experimental strategies for the elucidation of the membrane topology.

ATP-Binding Cassette Transporters↗