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PubMed2004

Advances in the development of common interchange standards for proteomic data.

The generation of proteomics data is increasingly high-throughput and high volume. Both experimental design and the technologies used to produce and subsequently analyze the data are becoming ever more complex. An increasing need for methods by which such data can be accurately described, stored and exchanged between experimenters and data repositories has been recognised. Work by the Proteomics Standards Initiative of the Human Proteome Organisation has laid the foundation for the development of standards by which experimental design can be described and data exchange facilitated. At a recent workshop in Nice, participants gathered to review the progress made to date and assist in pushing the process still further forward.

Humans↗

PubMed2006

Autumn 2005 Workshop of the Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) Geneva, September, 4-6, 2005.

The autumn workshop of the Proteomics Standards Initiative of the Human Proteomics Organisation met to further advance the development of the existing standards in the fields of molecular interactions and mass spectrometry. In addition, new areas were addressed, in particular developing standards for the description and exchange of data from gel electrophoresis experiments. The General Proteomics Standards group is now working closely with the FuGE (Functional Genomics Experiment) efforts to define a general standard in which to encode data that will enable a systems biology approach to data analysis. Common to all these efforts is the field of protein modifications, and work has been initiated to establish an ontology in this field that can be used by both workers in the field of proteomics and the wider scientific community.

Databases, Protein↗

PubMed2003

Filtering and selection of structural models: combining docking and NMR.

It is generally accepted that protein structures are more conserved than protein sequences, and 3D structure determination by computer simulations have become an important necessity in the postgenomic area. Despite major successes no robust, fast, and automated ab initio prediction algorithms for deriving accurate folds of single polypeptide chains or structures of intermolecular complexes exist at present. Here we present a methodology that uses selection and filtering of structural models generated by docking of known substructures such as individual proteins or domains through easily obtainable experimental NMR constraints. In particular, residual dipolar couplings and chemical shift mapping are used. Heuristic inclusion of chemical or biochemical knowledge about point-to-point interactions is combined in our selection strategy with the NMR data and commonly used contact potentials. We demonstrate the approach for the determination of protein-protein complexes using the EIN/HPr complex as an example and for establishing the domain-domain orientation in a chimeric protein, the recently determined hybrid human-Escherichia. coli thioredoxin.

Algorithms↗

PubMed2005

Spline-based non-parametric regression for periodic functions and its application to directional tuning of neurons.

The activity of neurons in the brain often varies systematically with some quantitative feature of a stimulus or action. A well-known example is the tendency of the firing rates of neurons in the primary motor cortex to vary with the direction of a subject's arm or wrist movement. When this movement is constrained to vary in only two dimensions, the direction of movement may be characterized by an angle, and the neuronal firing rate can be written as a function of this angle. The firing rate function has traditionally been fit with a cosine, but recent evidence suggests that departures from cosine tuning occur frequently. We report here a new non-parametric regression method for fitting periodic functions and demonstrate its application to the fitting of neuronal data. The method is an extension of Bayesian adaptive regression splines (BARS) and applies both to normal and non-normal data, including Poisson data, which commonly arise in neuronal applications. We compare the new method to a periodic version of smoothing splines and some parametric alternatives and find the new method to be especially valuable when the smoothness of the periodic function varies unevenly across its domain.

Action Potentials↗

PubMed1993

Alignment and searching for common protein folds using a data bank of structural templates.

We introduce an approach to protein comparisons in which tertiary-structure information is exploited in the alignment of a protein sequence of known tertiary structure, or an aligned set of sequences of known homologous structures, with one or more sequences. The local tertiary environments of residues in the one or more three-dimensional structures (defined in terms of residue accessibility to solvent, secondary structure and hydrogen bonding) are used to select position-specific amino acid substitution scores and produce a scoring template suitable for aligning sequences or searching sequence data banks. The amino acid substitution scores have been accumulated from 72 families of protein structures in which the observed substitutions have been classified according to features of the local structure. Hence, the value attributed to a particular amino acid interchange in the template is not a constant, but is dependent upon the environmental context in which that substitution has occurred. We have used these structural templates to align proteins, as well as to search an amino acid sequence data bank for proteins having a similar fold. Indeed, a database of templates that corresponds to both unique structures and aligned homologous structures from the Brookhaven Protein Data Bank has been produced. A new sequence can be searched against the database of templates in order to identify a similar tertiary fold even if the sequence is not significantly similar to any proteins of known three-dimensional structure.

Amino Acid Sequence↗

PubMed1999

Are brain functions really additive?

Although Positron Emission Tomography (PET) and functional magnetic resonance imaging (fMRI) studies commonly subtract data obtained during two or more experimental conditions to decompose a complex task, there have been few opportunities to evaluate this approach directly. In the present study, PET was used to study three motor speech tasks selected such that two were constituent components of the third, making possible a direct examination of decomposition by subtraction. In Experiment 1, a group of 13 right-handed normal volunteers participated in three activation studies: syllable repetition; phonation; and repetitive lip closure. A scanning session was devoted to a single task, repeated four times. In Experiment 2, six of the original subjects performed the same three activation studies during a single scanning session. Whether tasks were studied in separate scanning sessions or combined within a single session, the results of decomposition by compound subtraction differed significantly from the results obtained when individual tasks were compared to a simple baseline condition. These data failed to demonstrate task additivity, a necessary property if decomposition by subtraction is to provide an accurate characterization of the brain activity accompanying complex behavior.

Adult↗

PubMed2002

Distortion-free diffusion tensor imaging of cranial nerves and of inferior temporal and orbitofrontal white matter.

The main impact of functional neuroimaging has been its ability to locate neuronal activity either directly (EEG, MEG) or through the hemodynamic response caused by neuronal activity (PET, fMRI). In the past decade functional neuroimaging has been extended to investigate how brain regions interact, using the concepts of functional and effective connectivity. These concepts are further strengthened by estimates of anatomical connectivity of the same subject. A tool to determine anatomical connectivity in vivo may be provided by diffusion tensor imaging (DTI) methods. These can be used to determine the orientation of fiber bundles in white matter on the basis of the diffusion characteristics of water. Commonly, DTI data are acquired using echo planar imaging which suffers from susceptibility artifacts in orbitofrontal and inferior temporal cortex. Here we demonstrate the use of an alternative pulse sequence, diffusion-weighted single-shot STEAM, for assessing fiber orientation in orbitofrontal cortex and the cranial nerves. The scope of DTI needs to be extended to these structures to investigate psychiatric disorders in which orbitofrontal pathology or temporo-frontal disconnection have been postulated.

Adult↗

PubMed1991

Neurons of the pretectal area convey spinal input to the motor thalamus of the cat.

The aim of this study was to corroborate lesioning work (Mackel and Noda 1989), suggesting the pretectal area of the rostral midbrain acts as a relay between the spinal cord and the ventrolateral (VL) nucleus of the thalamus. For this purpose, extracellular recordings were made from neurons in the pretectal area which were antidromically activated by stimulation in the rostral thalamus, particularly in VL. The neurons were tested for input from the dorsal columns of the spinal cord, the dorsal column nuclei, and the ventral quadrant of the spinal cord. Latencies of the antidromic responses ranged between 0.6 and 3.0 ms (median 1.0 ms): no differences in latencies were associated with either location of the neurons in the pretectal area or with the site of their thalamic projection. Orthodromic responses to stimulation of ascending pathways were seen in the majority of neurons throughout the pretectal area sampled. Latencies of orthodromic responses varied considerably, with ranges of 0.9-9 ms, 6-20 ms, and 2.5-20 ms upon stimulating the dorsal column nuclei, dorsal columns, and ventrolateral quadrant, respectively. The shortest-latency responses to stimulation of the dorsal column nuclei or of the ventral quadrant were likely to be monosynaptic. Temporal and spatial facilitation of the responses to ascending input were common. The data show that neurons of the pretectal area are capable of relaying somatosensory input ascending from the spinal cord to the rostral thalamus. It is suggested that the pretectofugal output to VL converges with cerebellar input in VL neurons and becomes incorporated in cerebello-cerebral interactions and, ultimately, the control of movement.

Animals↗

PubMed1991

Role of quinolones in surgical prophylaxis.

The general principles involved in the use of chemoprophylaxis in surgery, the selection of patients at risk, and the choice of antibiotic agents are reasonably well established. While a good deal of data exist regarding commonly used prophylactic regimens, very little data are available on the role of quinolones in surgical prophylaxis. The literature dealing with this area is reviewed, and studies on the use of quinolones in biliary, colorectal, urologic, orthopedic and vascular surgery are discussed. The data suggest that generally the quinolones are as efficacious as the other antibiotics with which they were compared, and in the case of urologic surgery the results using quinolones were better than those in non-treated controls. Single-dose prophylaxis was regularly shown to be as effective as multiple dose regimens. Further clinical trial data are necessary before any firm conclusions can be drawn regarding the role of quinolones in surgical prophylaxis.

4-Quinolones↗

PubMedDate not supplied

Integrating occupational health into the medicine clerkship using problem-based learning.

OBJECTIVE: To improve medical students' ability and willingness to obtain occupational histories from their patients. PARTICIPANTS: General medicine faculty and internal medicine teaching residents, who participated as instructors, and medical students during their required internal medicine clerkships. SETTING: The primary teaching hospitals of two medical schools. DESIGN: During alternate months, students participated in problem-based sessions that included occupational health objectives (intervention) or attended the standard small-group didactic sessions (control). Process evaluations were collected from students and faculty in the intervention group following each session. Outcome evaluation was performed using chart audit and multiple-choice testing to compare the intervention and control groups. INTERVENTION: Intervention students participated in at least one problem-based session incorporating occupational aspects of disease into clinical internal medicine. Instructors received information packets and materials but had no other expertise in occupational medicine. MEASUREMENTS AND MAIN RESULTS: The great majority of ratings on the process evaluations showed that the students were "moderately" to "extremely" interested in the session attended. No student rated any session to be a "waste of time," and over 90% of students would recommend the session being evaluated to a friend. Chart audit showed that students in the intervention group recorded slightly more occupational information than did those in the control group (an average of 2.97 vs. 2.37 pieces of information, p = 0.06). When the most commonly documented data (employment status and job title) were ignored, the difference between group means (1.1 vs. 0.91) was significant (p = 0.03), suggesting that intervention students were more likely to probe further into a patient's occupational history. Both groups of students collected less occupational information from women than from men (t = 3.22, p = 0.0035). Multiple-choice tests revealed no difference between the two groups in overall medical knowledge or occupational medicine knowledge. CONCLUSIONS: Problem-based learning with specific occupational content is well accepted by students and modestly improves their occupational history taking.

Clinical Clerkship↗

PubMed2004

Mitochondrial DNA sequence variation in the Anatolian Peninsula (Turkey).

Throughout human history, the region known today as the Anatolian peninsula (Turkey) has served as a junction connecting the Middle East, Europe and Central Asia, and, thus, has been subject to major population movements. The present study is undertaken to obtain information about the distribution of the existing mitochondrial D-loop sequence variations in the Turkish population of Anatolia. A few studies have previously reported mtDNA sequences in Turks. We attempted to extend these results by analysing a cohort that is not only larger, but also more representative of the Turkish population living in Anatolia. In order to obtain a descriptive picture for the phylogenetic distribution of the mitochondrial genome within Turkey, we analysed mitochondrial D-loop region sequence variations in 75 individuals from different parts of Anatolia by direct sequencing. Analysis of the two hypervariable segments within the noncoding region of the mitochondrial genome revealed the existence of 81 nucleotide mutations at 79 sites. The neighbour-joining tree of Kimura's distance matrix has revealed the presence of six main clusters, of which H and U are the most common. The data obtained are also compared with several European and Turkic Central Asian populations.

Asian People↗

PubMed2005

Influence of photon scattering and attenuation on ROI analysis in brain perfusion single-photon emission tomographic imaging of normal subjects.

OBJECTIVE: The aim of this study was to evaluate the effect of scatter and attenuation correction in region of interest (ROI) analysis in brain perfusion single-photon emission tomography (SPECT) and to assess the influence of selecting the reference area on semi-quantification. METHODS: Ten normal subjects were enrolled and injected with 123I-iodoamphetamine to undergo simultaneous emission and transmission scanning for scatter and attenuation correction. We reconstructed three SPECT images from common projection data of each subject: with scatter correction and non-uniform attenuation correction, with scatter correction and uniform attenuation correction, and with uniform attenuation correction applied to data without scatter correction. A program for automated ROI drawing was used to set ROIs on various regions in brain images. Regional count ratios were compared in images with different correction procedures by using three different reference areas. RESULTS: The effect of the combination of scatter and attenuation correction was marked in the precentral, temporal, posterior, hippocampus and especially in the cerebellum. In contrast, it was not appreciable in the central and parietal areas. When using the cerebellar ROI as the reference, the count ratio varied widely depending on the correction procedures. On the other hand, the whole brain reference offered the least variation in the count ratio. CONCLUSIONS: The influence of photon scattering and attenuation was dependent on regions. Since the count in the cerebellar ROI is greatly affected by photon scattering and attenuation, nonuniform attenuation correction combined with scatter correction deserves consideration when using the cerebellar ROI as the reference.

Algorithms↗

PubMed2001

Guidelines for neurosurgical trauma in Brazil.

This chapter emphasizes some aspects of the Brazilian Guidelines for the Assessment of Head Injury Patients, written based on the experience of the Emergency Service, Neurosurgical Division of the University of São Paulo Medical School Hospital, and sponsored by the Brazilian Society of Neurosurgery. These guidelines approach the management of head-injury patients from their initial assessment in the Emergency Room until the final suggested clinical or surgical management. The Brazilian Guidelines represents our efforts to provide the basis for a common unified data collection system, which may allow cooperative studies in the future.

Brain Injuries↗

PubMed2000

A mouse phenome project.

A community-wide effort to establish baseline phenotypic data on commonly used and genetically diverse inbred mouse strains and to provide the information through a publicly accessible database.

Animals↗

PubMed1998

Genetic factors in fibromyalgia syndrome.

Although familial occurrence of fibromyalgia syndrome (FMS) has been commonly observed, data on a genetic role in this condition are limited. A few studies have reported familial aggregation and association with HLA. We have studied genetic linkage of FMS with HLA in multicase families, and found a rather weak linkage of FMS with HLA (P < 0.029).

Fibromyalgia↗

PubMed2005

Intima-media thickness score from carotid and femoral arteries predicts the extent of coronary artery disease: intima-media thickness and CAD.

OBJECTIVES: In the present study we measured carotid and femoral intima-media thickness (IMT) by B-Mode ultrasonography, as well as angiographic extent and severity of coronary artery disease in patients referred for coronary arteriography, to assess the relation between individual IMT, scores incorporating IMT from the carotid and femoral arteries and the extent and severity of coronary artery disease. METHODS: Two hundred and two patients referred for elective coronary angiography underwent ultrasound imaging of both carotid and femoral arteries for IMT measurements. An IMT score was developed as the number of sites with abnormal IMT (range 0-8). Multiple regression analysis indicated that IMT score was independently related to Gensini score, age and glucose levels. A high risk IMT score predicted an extended coronary artery disease although a low or medium risk IMT score cannot exclude the possibility of multivessel disease. Also, a high risk group could predict the performance of revascularization procedures and all cardiovascular events during a follow-up of 14.5 +/- 2.4 months. CONCLUSIONS: IMT incorporating data from common and internal carotid artery, carotid bifurcation and femoral artery are well correlated with the extent of coronary atherosclerosis, much better than individual IMT. Patients with high IMT score usually have multivessel coronary artery disease and are at increased risk for subsequent cardiovascular events.

Age Factors↗

PubMed2005

Polar plot representation for frequency-domain analysis of fluorescence lifetimes.

We present applications of polar plots for analyzing fluorescence lifetime data acquired in the frequency domain. This graphical, analytical method is especially useful for rapid FLIM measurements. The usual method for sorting out and determining the underlying lifetime components from a complex fluorescence signal is to carry out the measurement at multiple frequencies. When it is not possible to measure at more than one frequency, such as rapid lifetime imaging, specific features of the polar plot analysis yield valuable information, and provide a diagnostic visualization of the participating fluorescent species underlying a complex lifetime distributions. Data are presented where this polar plot presentation is useful to derive valuable, unique information about the underlying component distributions. We also discuss artifacts of photolysis and how this method can also be applied to samples where each fluorescence species shows a continuous distribution of lifetimes. Polar plots of frequency-domain data are commonly used for analysis of dielectric relaxation experiments (Cole-Cole plots), which have proved to be exceptionally useful in that field for decades. We compare this analytical tool that is well developed and extensively used in dielectric relaxation and chemical kinetics to fluorescence measurements.

Journal Article↗

PubMed2005

Therapeutic options for patients with Hodgkin's disease and non-Hodgkin's lymphoma who relapse after autologous transplant.

Although autologous stem cell transplantation for Hodgkin's disease and non-Hodgkin's lymphoma has become a safe and effective therapy, relapses after transplant are common. Emerging data indicate that an increasing number of patients can be re-induced into durable complete remission. Conventional dose- salvage chemotherapy and single-agent monoclonal antibody treatment provided limited success, but combination chemotherapy-monoclonal antibody treatments, second autografts, and reduced-intensity conditioning allografts provide encouraging results. For some patients, the best strategy may consist of participation in phase I to II studies of novel agents. New strategies designed to prevent relapse after autograft include cytokine therapy such as interleukin-2 in combination with monoclonal antibodies and the use of autologous antilymphoma vaccines.

Clinical Trials as Topic↗