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At least 487 records · Page 27Linked to original sources
PubMed2006

Global and focal aspects of absence epilepsy: the contribution of genetic models.

The cortico-reticular theory of absence epilepsy explains the origin of the bilateral generalized spike-wave discharges (SWDs) characterizing absence seizures via a subcortical pacemaker that is responsible for both normal sleep spindles and pathological SWDs. This pacemaker is the reticular thalamic nucleus (RTN); it produces spontaneous oscillations together with thalamic relay cells and the cortex in an assembled thalamo-cortico-thalamic network. Recently, Meeren et al. [2002. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. Journal of Neuroscience 22, 1480-1495.] proposed a focal theory of absence epilepsy based on experimental findings in the WAG/Rij rat, a genetic model of absence epilepsy: the somatosensory cortex contains a focus that initiates a cascade of events that ultimately leads to the occurrence of the bilateral and generalized SWDs if the state of the thalamo-cortical circuitry is favorable. Pharmacological, neurochemical, and neurophysiological data are presented and reviewed here that suggest SWDs might emerge from spontaneous oscillating neurons in the somatosensory cortex during both wakefulness and drowsiness. There is evidence for a variety of neurobiological changes, including a deficient global (parvalbumin) and local GABA-ergic (neurophysiological) system in the neocortex, which may explain why specifically the perioral region of the somatosensory cortex is hyperexcitable and the initiation site of 10Hz oscillations. The neuronal cortical and subcortical circuitry that produces SWDs is part of a large oscillatory system involved in generating cerebral rhythms associated with vibrissal movements. It needs to be established whether similar or comparable pathophysiological processes are also present in humans. Our hypothesis can be readily tested in other models and in humans considering that it is very specific and can be subjected to experimental verification.

Animals↗
PubMed1997

Intensity-modulated radiotherapy by means of static tomotherapy: a planning and verification study.

There is currently much research interest in developing, evaluating, and verifying intensity-modulation techniques. Of particular interest is how well the delivery of intensity-modulated profiles can be simulated by planning algorithms, and how accurately these profiles can be delivered given the specification constraints of linear accelerators. In this paper we present a planning and verification study based on delivering radiation in "static-tomotherapy" mode via the NOMOS MIMiC (Multileaf intensity-modulation collimator), which sheds some light on these issues. An inverse-planning algorithm was used to compute intensity-modulated profiles for a 9-coplanar-field plan for a body phantom. The algorithm makes several approximations about the form of the elementary fluence profile through bixels during delivery. Specifically, it is independent of the state of adjacent bixels (i.e., open or closed) and obeys the superposition principle. From the standpoint of comparing the predicted versus the delivered dose, these assumptions were made irrelevant by a final one-step forward dose calculation performed using the optimized intensity profiles. This forward dose calculation took into account the penumbral characteristics of the delivery system by decomposing the intensity profiles into the set of delivery components. Each component was assigned the appropriate penumbral functions thereby ensuring that the calculated dose distribution closely predicted the delivered dose distribution. The nine intensity modulated fields were delivered to a perspex phantom with the same geometry, containing a verification film. In general good agreement was found between the predicted and the measured delivered dose distributions. All the main features of the predicted dose distribution are seen in the delivered. The 90% isodoses were consistently in spatial agreement to within 3 mm. At the 50% isodose level consistent spatial agreement was again found to within 3 mm, the largest deviation being about 5 mm. The close correspondence between the predicted and measured dose distribution demonstrates the potential of the MIMiC delivery system. Our results indicate the level of dose conformation that is achievable in practice and the accuracy of the dose computation algorithm. However, this study only concerned delivery of radiation to a 2 cm thick slice, and the dose distribution was only verified in the central plane of the phantom where the film was placed. We therefore cannot comment as yet on what happens to the dose distribution away from the central film-plane.

Algorithms↗
PubMedDate not supplied

[Recognition of the potential SF-1 binding sites by SiteGA method, their experimental verification and search for new SF-1 target genes].

The SF-1 (Steroidogenic Factor-1) is a transcription factor known as a key regulator of the steroidogenic gene expression. SF-1 is required for the development and functioning at all levels of the hypothalamic-pituitary-gonadal and adrenal axis. Also it plays an essential role in sex determination. SF-1 is a member of the nuclear receptor superfamily and it activates gene expression by binding to DNA in a monomeric form. Here, we report the results of potential SF-1 binding sites identification by using the SiteGA recognition method. The SiteGA method was implemented using a genetic algorithm (GA) involving a iterative discriminant analyses of local dinucleotide context characteristics. These characteristics were compiled not only over the core binding sites region but over its flanks as well. Developed SiteGA method is characterized by considerably better recognition accuracy when compared to that for the weight matrix method. The experimental tests demonstrated that 83% of the sites recognized by the SiteGA method in the regulatory regions of steroidogenic genes, indeed, interact with the SF-1 factor. We also estimated the density of predicted sites in regulatory region of genes, the members of different functional groups and developed the criterion to search for new SF-1 target genes in genome sequences.

Algorithms↗
PubMed2002

High-throughput single-nucleotide polymorphism genotyping by fluorescent competitive allele-specific polymerase chain reaction (SNiPTag).

Single nucleotide polymorphisms (SNPs) are becoming widely recognized as the new currency for gene mapping as increasing numbers are discovered. Here we outline a method for their rapid analysis based on an allele-specific polymerase chain reaction (PCR) which employs a competitive approach, whereby both allele-specific primers are present in the same reaction and carry different fluorescent labels. This procedure is simple and amenable to high-throughput genotyping using conventional automated sequencing equipment, and no post-PCR modifications are required. Verification of the procedure was carried out by comparison of results derived by this method with those from restriction enzyme digestion of the ALDH2 exon 12 functional polymorphism (Glu-487-Lys) in 109 individuals. Additionally, we have examined all combinations of nucleotide substitutions and shown them to be differentiated by this method. As proof of concept, several assays were combined and loaded on a single gel lane/capillary to substantially improve throughput. This was made possible by designing the PCR products to be of different lengths and no interference was observed between products differing in size by only six nucleotides. We outline a number of test assays for well-characterized SNPs in human candidate genes for behavioral disorders.

Aldehyde Dehydrogenase↗
PubMed1997

Subcortical aphasia and the problem of attributing functional responsibility to parts of distributed brain processes.

N&C's discussion is, in places, an exemplar of the sort of rigor and attention to detail that will bring us closer to an understanding of the functional organization of the brain. Indeed, it is this level of work that pushes us to reflect on the assumptions that undergird our research efforts. Our criticisms have developed four main points. First, the level of rigor applied to the consideration of basal ganglionic aphasia should extend to each application of the CPC method (thalamic aphasia included). Second, in our haste to identify specific brain systems with distinct cognitive functions we should not neglect the more basic question of the causal mechanisms by which the brain organizes behavior. Questions of "direct" versus "indirect" involvement of a particular organ in a cognitive function are only likely to distract our attention from this more basic and less inferentially perilous issue. Third, pure cases should no longer be considered touchstones against which all behavioral disturbances are measured. Reifying such ideals is more likely to shroud than reveal the brain's true complexity. Finally, the functions that we enshrine in particular brain regions should explain the particular character of the symptoms observed when they are damaged and should admit of independent verification.

Aphasia, Broca↗
PubMed1986

Portable and desktop microcomputers for patient care charting.

Microcomputers are perfectly suited for the input, storage, display, and printing of medical information. The most efficient method of data input and verification is by health professionals themselves, at the bedside or in the exam room. Battery-powered microcomputers are now available with all the power and function of desktops. One patient-care software package [Smart-Chart(tm)] allows entry of clinical data into battery-powered computers such as the Epson Geneva or Data General One, and two-way communication of such data with IBM-PC compatibles. This system inexpensively places a complete computer system in the hands of health professionals in all locations of practice (even at home for use during telephone calls). A dozen or so floppy disks can allow primary physicians to have immediate access to current information on all patients in their practice. Medical notation by computer may now achieve its full potential for clarifying medical records, improving patient care, and diminishing the frustration of medical practice.

Attitude to Computers↗
PubMed2006

Verification of Onsager's reciprocal relations for evaporation and condensation using non-equilibrium molecular dynamics.

Non-equilibrium molecular dynamic (NEMD) simulations have been used to study heat and mass transfer across a vapor-liquid interface for a one-component system using a Lennard-Jones spline potential. It was confirmed that the relation between the surface tension and the surface temperature in the non-equilibrium system was the same as in equilibrium (local equilibrium). Interfacial transfer coefficients were evaluated for the surface, which expressed the heat and mass fluxes in temperature and chemical potential differences across the interfacial region (film). In this analysis it was assumed that the Onsager reciprocal relations were valid. In this paper we extend the number of simulations such that we can calculate all four interface film transfer coefficients along the whole liquid-vapor coexistence curve. We do this analysis both for the case where we use the measurable heat flux on the vapor side and for the case where we use the measurable heat flux on the liquid side. The most important result we found is that the coupling coefficients within the accuracy of the calculation are equal. This is the first verification of the validity of the Onsager relations for transport through a surface using molecular dynamics. The interfacial film transfer coefficients are found to be a function of the surface temperature alone. New expressions are given for the kinetic theory values of these coefficients which only depend on the surface temperature. The NEMD values were found to be in good agreement with these expressions.

Journal Article↗
PubMed2004

A new method of ozone forecasting using fuzzy expert and neural network systems.

This study describes the method of forecasting daily maximum ozone concentrations at four monitoring sites in Seoul, Korea. The forecasting tools developed are fuzzy expert and neural network systems. The hourly data for air pollutants and meteorological variables, obtained both at the surface and at the high elevation (500 hPa) stations of Seoul City for the period of 1989-1999, were analyzed. Two types of forecast models are developed. The first model, Part I, uses a fuzzy expert system and forecasts the possibility of high ozone levels (equal to or above 80 ppb) occurring on the next day. The second model, Part II, uses a neural network system to forecast the daily maximum concentration of ozone on the following day. The forecasting system includes a correction function so that the existing model can be updated whenever a new ozone episode appears. The accuracy of the forecasting system has been improved continuously through verification and augmentation.

Journal Article↗
PubMed2002

Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study.

Microarray studies can be used to examine expression levels for large numbers of genes simultaneously and may be applied to identify genes involved in schizophrenia. A microarray with 1127 brain-relevant genes was used to screen relative gene expression in the dorsolateral prefrontal cortex (DLPFC) from three pools of patients with schizophrenia (n = 15) and three matched control pools (n = 15). Pooling of tissue samples was employed as a strategy to detect changes in gene expression that are consistently found across individual cases of schizophrenia. Differences in gene expression were examined by z-ratios in addition to traditional normalized ratios. Three genes that showed consistently decreased expression in schizophrenia by both z-ratio differences and decreased normalized numerical ratios were identified. These were histidine triad nucleotide-binding protein (HINT), ubiquitin conjugating enzyme E2N (UBE2N) and glutamate receptor, ionotropic, AMPA 2 (GRIA2). Moreover, HINT gene expression was decreased to a similar degree in a prior study. In addition, a decrease in AMPA receptor expression is consistent with a decrease in glutamate synaptic function. These results are subject to limitations based on variations inherent to human subjects and tissue samples, possible effects of neuroleptic treatment, and the requirement for verification using independent techniques.

Adult↗
PubMed2006

Scale dependence of branching in arterial and bronchial trees.

Although models of branching in arterial and bronchial trees often predict a dependence of bifurcation parameters on the scale of the bifurcating vessels, direct verification of this dependence by comparison with data is uncommon. We compare measurements of bifurcation parameters of airways and arterial trees of different mammals as a function of scale to general features predicted by theoretical models based on minimization of pumping power and network volume. We find that the size dependence is more complex than existing theories based solely on energy and volume minimization explain, and suggest additional factors that may govern the branching at different scales.

Animals↗
PubMed1989

ampG is essential for high-level expression of AmpC beta-lactamase in Enterobacter cloacae.

Mutants of Enterobacter cloacae 55 were studied to delineate more completely the genetics of inducible expression of AmpC beta-lactamase. E. cloacae 55M-L, derived by mutagenesis from a mutant with high-level cefotaxime resistance (MIC, greater than 64 micrograms/ml), E. cloacae 55M, demonstrated a novel phenotype by producing only low levels of AmpC constitutively. Neither the parental phenotype of E. cloacae 55M nor the wild-type phenotype of E. cloacae 55 could be restored in E. cloacae 55M-L by the introduction of functional ampR, ampC, or ampD genes. Cloning each of these genes from E. cloacae 55M-L confirmed the same genotype for this mutant as for its parental strain. Mutation of E. cloacae 55M-L to the E. cloacae 55M phenotype was found to occur spontaneously at a frequency of 10(-8). All such revertants demonstrated an inducible wild-type phenotype after introduction of a functional ampD. These results suggested that the E. cloacae 55M-L phenotype was due to a mutation in an as yet unrecognized gene, designated ampG. Verification of this gene was obtained by the restoration of the E. cloacae 55M phenotype in E. cloacae 55M-L by introduction of a cloned 2.9-kilobase BamHI fragment from the E. cloacae 55 chromosome. Transformation of both ampG and ampD into E. cloacae 55M-L reconstituted the inducible wild-type phenotype. These results indicate that ampG is required for the activation of ampC by AmpR. Without ampG, neither induction nor high-level expression of AmpC is possible. It is likely that the ampG gene product and AmpD together modulate the ability of AmpR to activate ampC expression.

Ampicillin↗
PubMed1988

A compensation method for membrane-covered (Clark) electrodes.

Membrane-covered electrodes (Clark electrodes) are widely used for monitoring blood gases, particularly PO2. A method of compensating for the inherently limited speed of response of Clark electrodes is presented. The theoretical response in the time domain is related to that in the frequency domain, and the latter is deduced from measurement of the former. Although the response functions are both infinite series, both responses are nevertheless completely defined by a single time parameter Te characteristic of the electrode under given measurement conditions. Practical verification was performed using electrodes in the double-pulsed mode, but the theory is applicable equally to direct-current-polarized and simply pulsed electrodes.

Algorithms↗
PubMed2005

Multiple scattering by the iterative Foldy-Lax scheme.

The Foldy-Lax multiple-scattering equations in matrix form were examined for their suitability for solving the phase function and degree of linear polarization of clusters of particles as a complementary approach to the superposition T-matrix scheme. The constituent particles used for verification against the latter method were spheres with size parameters close to unity, with their aggregation governed by generalized Brownian motion. The number of constituents can be enlarged beyond the limitations of the benchmark method by a relatively small sacrifice in accuracy, but increasing constituent size and introducing nonsphericity easily result in numerical noise and overwhelming computational effort unless a large amount of the accuracy is going to be traded off.

Journal Article↗
PubMed2004

Wavelength-controlled variable-order optical fractional Fourier transform.

The relationship between optical fractional Fourier transforms (OFRTs) obtained at different wavelengths is derived by use of the ABCD matrix formalism. It is shown that varying the wavelength while retaining the same optical system can be used to control the order of the OFRT. The advantage of this method of varying OFRT order is that no variation in the characteristics of the bulk optics is required. A general experimental verification of the theory is provided by showing the exact equivalence of two OFRT systems of different order when they are replayed using the same input function at different wavelengths.

Journal Article↗
PubMed2005

Methods of dendritic cell preparation for acute lymphoblastic leukemia immunotherapy in children.

Cell immunotherapy through dendritic cells (DC) presents a hopeful strategy for the treatment of various tumors. The aim of our study was to find which progenitor cells are most suitable for the preparation of dendritic cells in acute lymphoblastic leukemia (ALL) in pediatric patients, whether blasts from bone marrow or dendritic cells generated from peripheral blood mononuclear cells taken at the time of remission after induction chemotherapy. DC generated from the BM blasts of patients with B-ALL and T-ALL (n = 15) at the time of diagnosis expressed low levels of costimulatory molecules and CD markers typical for mature DC. In contrast, DC cultivated from peripheral mononuclear cells of patients (n = 9) had comparable morphology and expression of costimulatory molecules to DC obtained from healthy individuals, which was even higher after tumor lysate pulsing. Autologous lymphocyte proliferation increased after DC blasts lysate pulsation and further after lymphocyte restimulation, showing evidence of induction of specific cytotoxic lymphocytes. When comparing both cell sources for the preparation of DC in patients with ALL, it appears that peripheral mononuclear cells obtained after chemotherapy are more suitable than bone marrow leukemic blasts due to similar morphology, phenotypic, and functional capacity to monocytes of healthy donors. Despite this, it is necessary to take into account individual variability when preparing DC-based vaccines. The final verification of the efficiency of immunotherapy against residual hematopoietic malignant cells in patients with ALL can only be obtained through a clinical study.

Adolescent↗
PubMedDate not supplied

Mechanisms of the immunosuppressive and anti-inflammatory effects of glucocorticosteroids.

Corticosteroids have multifaceted effects on various phases of inflammatory and immunological activity. These include effects on vascular and tissue responses, effects on the movement or traffic of inflammatory or immunologically reactive cells, direct effects on functional capabilities of cells, and direct or indirect effects on various soluble factors mediating inflammation or immunologic activity. It is clear that there is a differential sensitivity of various populations and subpopulations of cells to the corticosteriod modulation of cellular kinetic patterns, cellular interactions, and functional capabilities. In general, corticosteroids have a much greater and more obvious effect on the traffic and kinetics than on the functional properties of cells involved in inflammation and immunologic activity. Hypotheses concerning the precise mechanisms of many of these effects have been proposed, but still await verification and possibly amplification.

Animals↗
PubMedDate not supplied

Conversion prosthesis: a transitional fixed implant-supported prosthesis for an edentulous arch--a technical note.

A technique for fabricating a provisional fixed prosthesis for an edentulous arch immediately following abutment connection, termed conversion prosthesis, is described in detail. Advantages of the restoration include the following: it provides a fixed prosthesis immediately following stage 2 surgery with improved function, stability, and distribution of load; it protects the sutured mucosa; it serves as a prototype for the final prosthesis; it can be used as a verification jig; it preserves the original vertical dimension of occlusion; it aids in obtaining and transferring the interocclusal record; it assists long-term patient maintenance; and it reduces treatment visits. The advantages of its use clearly outweigh the disadvantages.

Acrylic Resins↗
PubMed1986

[Verification of smoking habits in group studies by anamnesis or determination of serum thiocyanate level?].

In an unselected series of 336 patients of our clinic for occupational diseases a standardized questionnaire on respiratory symptoms and measurements of lung function (spirometry, body plethysmography, flow-volume-curve) were used to study the relations of these results to smoking habits evaluated by questionnaire or thiocyanate level. Statistical elaboration revealed closer connections between anamnestic data on smoking habits and respiratory impairment than between the latter and thiocyanate level. In conclusion anamnestic data on smoking habits are more reliable than thiocyanate measurements in occupational field studies.

Adult↗