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At least 523 records · Page 29Linked to original sources
PubMed2005

Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.

In both genetic and idiopathic forms of Parkinson's disease (PD), considerable evidence supports the involvement of alpha-synuclein, electron transport chain complex I, protein aggregation, and the ubiquitin-proteasome system. To investigate alterations in the transcription of genes that comprise these pathways, we performed gene expression profiling and functional gene group analysis of three brain regions (the substantia nigra, putamen, and area 9) in postmortem tissue from matched groups of PD or control subjects (n = 15/group). Verification of selected changes was performed using RT-PCR, and visualization of selected changes in expression was accomplished using in situ hybridization (ISH). Our results provide strong support for the impairment of multiple electron transport chain complexes and the ubiquitin-proteasomal system in PD, along with a robust induction of heat shock proteins and some anti-apoptotic gene groups. Several novel gene and gene group findings were also obtained that offer new insight into the pathogenesis and potential treatment of PD.

Aged↗
PubMed2005

Wavelet transformation based watermarking technique for human electrocardiogram (ECG).

Nowadays, watermarking has become a technology of choice for a broad range of multimedia copyright protection applications. Watermarks have also been used to embed prespecified data in biomedical signals. Thus, the watermarked biomedical signals being transmitted through communication are resistant to some attacks. This paper investigates discrete wavelet transform based watermarking technique for signal integrity verification in an Electrocardiogram (ECG) coming from four ECG classes for monitoring application of cardiovascular diseases. The proposed technique is evaluated under different noisy conditions for different wavelet functions. Daubechies (db2) wavelet function based technique performs better than those of Biorthogonal (bior5.5) wavelet function. For the beat-to-beat applications, all performance results belonging to four ECG classes are highly moderate.

Algorithms↗
PubMed1998

Spontaneous liposome formation induced by grafted poly(ethylene oxide) layers: theoretical prediction and experimental verification.

Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1, 2-diacyl-sn-glycerophosphocholines (e.g., egg L-alpha-lecithin, 1, 2-dimyristoyl-sn-glycero-3-phosphocholine, 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1, 2-distearoyl-sn-glycero-3-phosphocholine) and 1, 2-dipalmitoyl-sn-glycerophosphatidylethanolamine-PEO conjugates (i.e. , 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e glycol)2000]carboxamide and 1, 2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxypoly(e thylen e oxide)5000]carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersions, analyzed by quasielastic light scattering, solute retention, 31P NMR, and freeze-fracture electron microscopy measurements, confirmed the single chain mean field predictions. These data indicate that thermodynamically stable, unilamellar liposomes are formed spontaneously by simple hydration of fluid phase phospholipid bilayer films containing low molar ratios of PEO-based amphiphiles. They further suggest that the equilibrium size and colloidal properties of fluid phase, PEO-modified liposomes can be predicted by using this theoretical approach. The implication of these results on the design and processing of sterically stabilized liposomes used in drug delivery applications also is described.

1,2-Dipalmitoylphosphatidylcholine↗
PubMedDate not supplied

Probing sensory and associative semantics for animals and objects in normal subjects.

Neuropsychological studies of patients with "category-specific" semantic memory disorders have fuelled a debate concerning the organisation of knowledge. In particular it has been suggested that the reported double dissociation between knowledge of animals and living things on the one hand, and objects on the other, reflects a more fundamental division of semantic representation into functional-associative and sensory-visual domains. The present study attempted to investigate whether there were systematic differences along these dimensions in normal subjects using a sentence-verification technique. It was found that response times were significantly longer for verification of statements concerning the sensory attributes of objects than for statements about their associative attributes. In the case of animals, there were no differences in response latency to associative or sensory statements. In the light of this previously unreported fractionation within verbal semantics, the possible consequences for models of semantic memory are discussed.

Adult↗
PubMed1977

The radiology of ex vivo renal perfusion and autotransplantation.

The radiologic findings in 16 patients subjected to ex vivo renal perfusion and autotransplantation are reviewed. Preoperative excretion urography and renal arteriography are essential to define ureteral and arterial anatomy; renal scintiangiography and renography are useful for baseline studies. Plain radiographs should be obtained during nephrolithotomy. Intraoperative renal arteriography should be reserved for patients who require more precise definition of vascular anatomy or verification of adequate repair after a difficult dissection. Postoperative scintiangiography is required on the first day to exclude arterial occlusion. Renography and urography to evaluate autotransplant anatomy and function should be deferred for about 3 weeks, unless there is clinical evidence of a complication.

Angiography↗
PubMed2004

Verification of skin-based markers for 3-dimensional kinematic analysis of the equine tarsal joint.

REASONS FOR PERFORMING STUDY: Kinematic studies are usually based on tracking markers attached to the skin. However, complex joints, such as the tarsal joint, function in 3-dimensions (3D), and have therefore necessitated application of the invasive bone pin technique, limiting kinematic studies to the research laboratory. This study investigates the feasibility of using skin-based markers for 3D analysis of tarsal joint motion. HYPOTHESIS: Three-dimensional motions of the tarsal joint can be measured with an acceptable degree of accuracy using skin markers. METHODS: Retroreflective markers were attached over the tibial and metatarsal segments. Markers were tracked automatically at trot. Three-dimensional skin correction algorithms were used for correction of skin displacement, and 3D motions derived from the corrected (CSD) and uncorrected (USD) skin displacement were compared with data from a previous study in which those motions were described using bone-fixed markers (BFM) by correlation, root mean square errors (RMS) and shape agreement (SA) of the curves. RESULTS: The RMS of BFM and CSD were smaller than those of BFM and USD for all motions. The correlation coefficients of BFM and CSD were higher than those of BFM and USD. SA was good or fair for all motions except internal/external rotation and medial/lateral translation. CONCLUSIONS AND POTENTIAL RELEVANCE: With appropriate correction for skin movement relative to skeletal landmarks, skin markers can identify tarsal 3D motions for flexion/extension, abduction/adduction, cranial/caudal translation, and proximal/distal translation, allowing analysis and comparison of information between horses during swing and stance phases.

Algorithms↗
PubMed2004

[New chapter in the study of visual evoked potentials--clinical application of the multifocal VEP method].

The multifocal visual evoked potentials are the evoked responses over the visual cortex in response to the stimulation of circumscribed small areas in the central 30 degree region of the retina. The recording of multifocal visual evoked potentials was made possible by the computer algorhythm elaborated by Sutter in 1991. Multifocal electroretinography, developed upon the same theoretical principles, is already an routine clinical examination method for the topographic analysis of functional damages in the central part of the retina and for the differential diagnostics in neuro-ophthalmology. The multifocal visual evoked potential, however, has not been introduced into the clinical practice, although it displays the function of ganglion cells in a given region of the retina in a more detailed way than the sensitivity threshold in the perimetry. This examination makes the objective verification of defects possible in the visual pathway, too. In our department the recording of multifocal visual evoked potentials was started in 2002. In this paper we present the basics of this method and also deal with the problems concerning its application and its status in the history of visual evoked potentials.

Electroretinography↗
PubMedDate not supplied

Gender verification of female athletes.

The International Olympic Committee (IOC) officially mandated gender verification for female athletes beginning in 1968 and continuing through 1998. The rationale was to prevent masquerading males and women with "unfair, male-like" physical advantage from competing in female-only events. Visual observation and gynecological examination had been tried on a trial basis for two years at some competitions leading up to the 1968 Olympic Games, but these invasive and demeaning processes were jettisoned in favor of laboratory-based genetic tests. Sex chromatin and more recently DNA analyses for Y-specific male material were then required of all female athletes immediately preceding IOC-sanctioned sporting events, and many other international and national competitions following the IOC model. On-site gender verification has since been found to be highly discriminatory, and the cause of emotional trauma and social stigmatization for many females with problems of intersex who have been screened out from competition. Despite compelling evidence for the lack of scientific merit for chromosome-based screening for gender, as well as its functional and ethical inconsistencies, the IOC persisted in its policy for 30 years. The coauthors of this manuscript have worked with some success to rescind this policy through educating athletes and sports governors regarding the psychological and physical nature of sexual differentiation, and the inequities of genetic sex testing. In 1990, the International Amateur Athletics Federation (IAAF) called for abandonment of required genetic screening of women athletes, and by 1992 had adopted a fairer, medically justifiable model for preventing only male "impostors" in international track and field. At the recent recommendation of the IOC Athletes Commission, the Executive Board of the IOC has finally recognized the medical and functional inconsistencies and undue costs of chromosome-based methods. In 1999, the IOC ratified the abandonment of on-site genetic screening of females at the next Olympic Games in Australia. This article reviews the history and rationales for fairness in female-only sports that have led to the rise and fall of on-site, chromosome-based gender verification at international sporting events.

Chromatin↗
PubMed2002

Verification of 525 coding SNPs in 179 hypertension candidate genes in the Japanese population: identification of 159 SNPs in 93 genes.

Single-nucleotide polymorphisms (SNPs) located in coding regions (coding SNPs; cSNPs) with amino acid substitution can potentially alter protein function. Therefore, identification of the nonsynonymous cSNPs of the genes of common diseases is valuable in tests of association with phenotypes. In this study, we validated 525 candidate cSNPs from 179 hypertension candidate genes deposited in the publicly available database dbSNP by DNA sequencing of samples from 32 Japanese individuals. We identified a total of 143 SNPs (27%) in 93 hypertension candidate genes. We also identified 16 new SNPs, for a total of 159 SNPs. Of the 159 SNPs thus identified, 104 were nonsynonymous. We estimate that approximately 20% of the SNPs deposited in dbSNP database showed a minor allele frequency of over 5%. The candidate SNPs for hypertension identified in this study would be valuable for association studies with hypertension to accelerate the identification of hypertension genes.

Gene Frequency↗
PubMed2001

Database verification studies of SWISS-PROT and GenBank.

PROBLEM STATEMENT: We have studied the relationships among SWISS-PROT, TrEMBL, and GenBank with two goals. First is to determine whether users can reliably identify those proteins in SWISS-PROT whose functions were determined experimentally, as opposed to proteins whose functions were predicted computationally. If this information was present in reasonable quantities, it would allow researchers to decrease the propagation of incorrect function predictions during sequence annotation, and to assemble training sets for developing the next generation of sequence-analysis algorithms. Second is to assess the consistency between translated GenBank sequences and sequences in SWISS-PROT and TrEMBL. RESULTS: (1) Contrary to claims by the SWISS-PROT authors, we conclude that SWISS-PROT does not identify a significant number of experimentally characterized proteins. (2) SWISS-PROT is more incomplete than we expected in that version 38.0 from July 1999 lacks many proteins from the full genomes of important organisms that were sequenced years earlier. (3) Even if we combine SWISS-PROT and TrEMBL, some sequences from the full genomes are missing from the combined dataset. (4) In many cases, translated GenBank genes do not exactly match the corresponding SWISS-PROT sequences, for reasons that include missing or removed methionines, differing translation start positions, individual amino-acid differences, and inclusion of sequence data from multiple sequencing projects. For example, results show that for Escherichia coli, 80.6% of the proteins in the GenBank entry for the complete genome have identical sequence matches with SWISS-PROT/TrEMBL sequences, 13.4% have exact substring matches, and matches for 4.1% can be found using BLAST search; the remaining 2.0% of E.coli protein sequences (most of which are ORFs) have no clear matches to SWISS-PROT/TrEMBL. Although many of these differences can be explained by the complexity of the DB, and by the curation processes used to create it, the scale of the differences is notable.

Algorithms↗
PubMed1993

Hierarchical functional organization of formal biological systems: a dynamical approach. III. The concept of non-locality leads to a field theory describing the dynamics at each level of organization of the (D-FBS) sub-system.

In paper I, the construction of the graph of interactions, called (O-FBS), was deduced from the 'self-association hypothesis'. In paper II, a criterion of evolution during development for the (O-FBS), which represents the topology of the biological system, was deduced from an optimum principle leading to specific dynamics. Experimental verification of the proposed extremum hypothesis is possible because precise knowledge of the dynamics is not necessary; only knowledge of the monotonic variation of the number of sinks is required for given initial conditions. Essentially, the properties of the (O-FBS) are based on the concept of non-symmetry of functional interactions, as shown by the 'orgatropy' function (paper II). In this paper, a field theory is proposed to describe the (D-FBS), i.e. the physiological processes expressed by functional interactions: (i) physiological processes are conceived as the transport of a field variable submitted to the action of a field operator; (ii) because of hierarchy, this field theory is based on the concept of non-locality, and includes a non-local and non-symmetric interaction operator; (iii) the geometry of the structure contributes to the dynamics via the densities of structural units; and (iv) because a physiological process evolves on a particular timescale, it is possible to classify the levels of organization according to distinct timescales, and, therefore, to obtain a 'decoupling' of dynamics at each level. Thus, a property of structurality for a biological system is proposed, which is based on the finiteness of the velocity of the interaction, thus, with distinct values of timescales for the construction of the hierarchy of the system. Three axioms are introduced to define the fields associated with the topology of the system: (i) the existence of the fields; (ii) the decoupling of the dynamics; and (iii) the ability of activation-inhibition. This formulation leads to a self-coherent definition of auto-organization: an FBS is self-organized if it goes from one stable state for the (D-FBS) to another under the influence of certain modifications of its topology, i.e. a modification of the (O-FBS). It is shown that properties deduced with this formalism give the relationship between topology and geometry in an FBS, and particularly, the geometrical re-distribution of units.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

A finite element musculoskeletal model of the shoulder mechanism.

The finite element method described in this study provides an easy method to simulate the kinetics of multibody mechanisms. It is used in order to develop a musculoskeletal model of the shoulder mechanism. Each relevant morphological structure has been represented by an appropriate element. For the shoulder mechanism two special-purpose elements have been developed: a SURFACE element representing the scapulothoracic gliding plane and a CURVED-TRUSS element to represent muscles which are wrapped around bony contours. The model contains four bones, three joints, three extracapsular ligaments, the scapulothoracic gliding plane and 20 muscles and muscle parts. In the model, input variables are the positions of the shoulder girdle and humerus and the external load on the humerus. Output variables are muscles forces subject to an optimization procedure in which the mechanical stability of the glenohumeral joint is one of the constraints. Four different optimization criteria are compared. For 12 muscles, surface EMG is used to verify the model. Since the optimum muscle length and force-length relationship are unknown, and since maximal EMG amplitude is length dependent, verification is only possible in a qualitative sense. Nevertheless, it is concluded that a detailed model of the shoulder mechanism has been developed which provides good insight into the function of morphological structures.

Acceleration↗
PubMed1991

Non-random cell killing in cryopreservation: implications for performance of the battery of leukocyte tests (BLT), I. Toxic and immunotoxic effects.

To eliminate between-tests error in longitudinal human studies, for specimen sharing, convenient scheduling, etc., it is necessary for us to freeze leukocytes as well as non-transformed, continuous T lymphocyte (CTL) lines. Two commonly used cryopreservation methods were compared in terms of efficacy. Isolated peripheral blood mononuclear cells and CTLs were each aliquoted into three sets of vials. Two sets each were frozen in a 1:1 mixture of 15% DMSO in Mixed Medium (MM) and 20% FBS in MM using a commonly employed styrofoam freezer insert method for liquid nitrogen refrigerators and a programmed freezer (temperature falls at an optimal rate), respectively. The remaining set was held in MM with 20% FBS at 20 degrees C during the 2-h freezing process. The cells were thawed and/or washed and assayed for viability and T helper (Th)/T suppressor (Ts) ratio. It is clear that inadequate freezing (via the styrofoam method) non-randomly damages cells of T cell subpopulations, Th being more sensitive than Ts. Further, it is shown that inadequate cryopreservation can confound results from a number of assessment methods owing to morphological and functional damages. The battery of leukocyte tests (BLT) under development in this laboratory, is designed to detect toxic, immunotoxic and genotoxic effects of in vivo mutagen exposure on human blood. It is concluded that minimization of non-random cell losses (as quantitated on the basis of morphology) and preservation of related regulatory cell function is essential if one would assess the in vivo and in vitro states of heterogeneous cells. Further, it is suggested that freezing methods should be used only after verification that selective damage to subpopulations is not occurring among cells that otherwise might wrongly be assumed to be intact.

Blood Component Removal↗
PubMed1979

Signal detection theory pain measures: empirical validation studies and adaptation-level effects.

Proponents of the use of signal detection theory (SDT) in the assessment of pain modulation have generally looked for changes in d' to indicate a reduction of sensory function, and a change in criterion to indicate a modification of the subject's response bias or attitudinal predisposition. In the first experiment, both assumptions failed to receive empirical verification. Discrimination d' was eqivalent before and after two strong levels of electrical current was reduced. The criterion parameter appeared to shift in a more conservative direction after the stimulus diminution. These results are used to question the validity of both detection and discrimination indices in the measurement of pain. An alternative means for describing the experimental results revealed a striking adaptation-level effect with implications for the assessment of both experimentally induced and endogenous pain. The outcome of a second experiment reinforced the adaptation-level theory interpretation of the results and provided additional evidence concerning the difficultuies in evaluating SDT parameters in studies of potential analgesics.

Discrimination, Psychological↗
PubMed2001

Circadian regulation of gene expression systems in the Drosophila head.

Mechanisms composing Drosophila's clock are conserved within the animal kingdom. To learn how such clocks influence behavioral and physiological rhythms, we determined the complement of circadian transcripts in adult Drosophila heads. High-density oligonucleotide arrays were used to collect data in the form of three 12-point time course experiments spanning a total of 6 days. Analyses of 24 hr Fourier components of the expression patterns revealed significant oscillations for approximately 400 transcripts. Based on secondary filters and experimental verifications, a subset of 158 genes showed particularly robust cycling and many oscillatory phases. Circadian expression was associated with genes involved in diverse biological processes, including learning and memory/synapse function, vision, olfaction, locomotion, detoxification, and areas of metabolism. Data collected from three different clock mutants (per(0), tim(01), and Clk(Jrk)), are consistent with both known and novel regulatory mechanisms controlling circadian transcription.

Animals↗
PubMed2005

Experimental characterization and physical modelling of the dose distribution of scanned proton pencil beams.

In this paper we present the pencil beam dose model used for treatment planning at the PSI proton gantry, the only system presently applying proton therapy with a beam scanning technique. The scope of the paper is to give a general overview on the various components of the dose model, on the related measurements and on the practical parametrization of the results. The physical model estimates from first physical principles absolute dose normalized to the number of incident protons. The proton beam flux is measured in practice by plane-parallel ionization chambers (ICs) normalized to protons via Faraday-cup measurements. It is therefore possible to predict and deliver absolute dose directly from this model without other means. The dose predicted in this way agrees very well with the results obtained with ICs calibrated in a cobalt beam. Emphasis is given in this paper to the characterization of nuclear interaction effects, which play a significant role in the model and are the major source of uncertainty in the direct estimation of the absolute dose. Nuclear interactions attenuate the primary proton flux, they modify the shape of the depth-dose curve and produce a faint beam halo of secondary dose around the primary proton pencil beam in water. A very simple beam halo model has been developed and used at PSI to eliminate the systematic dependences of the dose observed as a function of the size of the target volume. We show typical results for the relative (using a CCD system) and absolute (using calibrated ICs) dosimetry, routinely applied for the verification of patient plans. With the dose model including the nuclear beam halo we can predict quite precisely the dose directly from treatment planning without renormalization measurements, independently of the dose, shape and size of the dose fields. This applies also to the complex non-homogeneous dose distributions required for the delivery of range-intensity-modulated proton therapy, a novel therapy technique developed at PSI.

Calibration↗
PubMed1979

Development of a multifunctional drug file for hospital pharmacy computer applications.

The development of a multifunctional master drug file (MDF) which satisfies initial pharmacy data base requirements and has the capability to support increasingly sophisticated computer applications is described. The computerized purchasing, inventory, drug use review and formulary systems in a 1,100-bed teaching hospital were evaluated to determine which existing data fields should be included in the MDF, Functional requirements for the MDF and 27 data fields, each with its own particular specifications for programming, were identified. A method of data input was designed to create and maintain the file using keypunched Hollerith cards. Data input forms were designed to serve as coding documents for drug file data. Verification of all data in the file can be performed by running a program which lists the contents of each drug recorded. Based on 1975 salary rates, the total cost of the MDF development was $4,010; total time required was 640 hours. Approximately one hour per week is needed to keep the file contents up to date. File design specifications and contents are discussed, with special emphasis on the functional aspects of the MDF. The MDF successfully fulfilled the initaial pharmacy computer system requirements and has the potential to accommodate increasingly sophisticated applications.

Computers↗
PubMed2006

Rapid production of human KIR2DL4 extracellular domain and verification of its interaction with HLA-G.

Killer cell immunoglobulin-like receptor (KIR) 2DL4 is the only KIR member reported to be expressed by all human natural killer (NK) cells. It differs from other KIR members in both structure and function. Its specific interaction with HLA-G, a non-classical MHC class I molecule, has been suggested to play an important role in regulating NK cell-mediated cytotoxicity. However, this interaction is still in doubt. In addition, the soluble KIR2DL4 extracellular domain used in many studies was produced by eukaryotic expression, which is less efficient than prokaryotic expression. In this study, we describe a method of rapid production a large amount of soluble KIR2DL4 extracellular domain based on a prokaryotic expression system. With this soluble KIR2DL4, we verified the interaction between KIR2DL4 and HLA-G1.

Gene Expression↗