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PubMed2002

Enteroviruses identifications and differentiation on the basis of the selective group--specific inhibitory effect of chemical compounds.

Two new enteroviruses (EV) inhibitors with the selective group-specific effect were detected and studied representing the products of the original chemical synthesis. One of them--nifan (arylfuran derivative) inhibits poliomyelitis virus replication, the other one--belvtazide (synchonic acid derivative) blocks non-poliomyelitis EV (ECHO and Coxsackie B) replication. The study of the reference strains of poliomyelitis virus type 1-3, twenty-three ECHO virus types (from the 1st to the 33rd), Coxsackie B virus type 1-6 and 288 primary EV isolates did not reveal type or strain specific variability in the inhibitors effect. Nifan and belvtazide supress the replication of both EV monostrains and their mixtures. The isolates of mixed nature are inhibited by the mixture nifan + belvtazide. At the same time neither separate chemicals nor their blend affects viruses from other families (Adenoviridae, Orthomyxoviridae, Herpesviridae etc.). The mechanism of nifan and belvtazide action is intracellular EV replication inhibition (they do not affect the process of virus adsorption and penetration into the cell), suppression of de novo virus synthesis by 7.0-2.25 lg (tissue culture infective dose 50 per cent) TCID50/ml and of virus-induced RNA synthesis. The drugs feature is high selectivity (90-91%) regarding RNA polioviruses (nifan) and RNA non-poliomyelitis EV (belvtazide). Nifan and belvtazide antiviral effect selectivity allows unknown cytopathic agents (CPA) belonging to the EV to be established with the high degree (over 98%) of reproducibility at the stage of primary identification with the differentiation of poliomyelitis and non-poliomyelitis viruses.

Antiviral Agents↗
PubMed2003

Time-resolved fluorescence allows selective monitoring of Trp30 environmental changes in the seven-Trp-containing human pancreatic lipase.

Human pancreatic lipase (HPL, triacylglycerol acylhydrolase, EC 3.1.1.3) is a carboxyl esterase which hydrolyzes insoluble emulsified triglycerides and is essential for the efficient digestion of dietary fats. Though the three-dimensional structure of this enzyme has been determined, monitoring the conformational changes that may accompany the binding of various substrates and inhibitors is still of interest. Because of its sensitivity and ease of use, fluorescence spectroscopy of the intrinsic Trp residues is ideally suited for this purpose. However, the presence of seven Trp residues spread all over the HPL structure renders the interpretation of the fluorescence changes difficult with respect to the identification and location of the conformational or environmental changes taking place at the various Trp residues. In this context, the aim of this work was to investigate the contribution of the individual Trp residues to the fluorescence properties of HPL. To this end, we analyzed the steady-state and time-resolved fluorescence parameters of five single-point mutants in which one Trp residue was substituted with a weakly fluorescent Phe residue. In addition to the Trp residues at positions 30, 86, and 252, strategically located with respect to the active site, we also mutated Trp residues at positions 17 and 402, as representative residues of the HPL N- and C-terminal domains, respectively. Taken together, our data suggested that the solvent-exposed Trp30 residue contributed to at least 44% of the overall fluorescence of wild-type HPL. Moreover, we found that the long-lived fluorescence lifetime (6.77 ns) of wild-type HPL could be specifically attributed to Trp30, a feature that enables selective monitoring of its environmental changes. Additionally, Trp residues at positions 17 and 402 strongly contributed to the 1.61 ns lifetime of HPL, while Trp residues at positions 86 and 252 contributed to the 0.29 ns lifetime.

Base Sequence↗
PubMed1999

Visual attention deficits in Alzheimer's disease: simple versus conjoined feature search.

The authors investigated selective attention in patients with Alzheimer's disease (AD), using a well-known visual search procedure. In simple feature search, the deficit observed in AD patients represented a baseline shift in the median hit reaction time (RT). On the conjoined feature search task, the median hit RT for AD patients increased disproportionately with increasing array size, indicating an additional cognitive impairment on this task. Of particular importance, the cognitive deficit observed in conjunction search was more profound than that predicted on the basis of previous reports of global cognitive slowing in AD. There was some evidence that the performance of AD patients improved more than the performance of controls over the duration of the experimental test session. Patients also had more difficulty in detecting targets on the right side of hemispace and in more peripheral locations.

Adolescent↗
PubMed1998

Electronic structural information from Q-band ENDOR on the type 1 and type 2 copper liganding environment in wild-type and mutant forms of copper-containing nitrite reductase.

Q-band ENDOR elucidated proton and nitrogen hyperfine features to provide spin density information at ligands of blue-green Type 1 and catalytic Type 2 copper centers in nitrite reductase. The blue-green Type 1 center of nitrite reductase has a redox, electron-transfer role, and compared to the blue center of plastocyanin, it has the following structural differences: a shortened Cu-Smet bond length, a longer Cu-Scys bond length, and altered ligand-copper-ligand bond angles (Adman, E. T., Godden, J. W., and Turley, S. (1995) J. Biol. Chem. 270, 27458-27474). The hyperfine couplings of the two Type 1 histidine (N delta) ligands showed a larger percentage difference from each other in electron spin density than previously reported for other blue Type 1 proteins, while the cysteine beta-proton hyperfine couplings, a measure of unpaired p pi spin density on the liganding cysteine sulfur, showed a smaller electron spin density. A mutation of the Type 1 center, M182T, having the copper-liganding Met182 transformed to Thr182, caused the center to revert to an optically "blue" center, raised its redox potential by approximately 100 mV, and led to the loss of activity (prior paper). Surprisingly, in M182T there was no change from native Type 1 copper either in the histidine or cysteine hyperfine couplings or in g values and Cu nuclear hyperfine couplings. The conclusion is that the optical and redox alterations due to changed Type 1 methionine ligation need not be concurrent with electron spin delocalization changes in the HOMO as reported from its essential cysteine and histidines. A detailed picture of the nitrogen couplings from the three histidine (N epsilon) ligands of the Type 2 center indicated a substantial ( approximately 200%) electronic hyperfine inequivalence of one of the histidine nitrogens from the other two within the Type 2 HOMO and thus provided evidence for electronic distortion of the Type 2 site. In the presence of the nitrite substrate, hyperfine couplings of all histidines diminished. We suggest that this nitrite-induced decreased covalency would correlate with an increased Type 2 redox potential to assist electron transfer to the Type 2 center. Dipole-coupled, angle-selected exchangeable proton features, observed over a range of g values, predicted a ligand-water proton distance of 2.80 A from copper, and these water protons were eliminated by nitrite. His287 is not a Type 2 ligand but is positioned to perturb an axial water or a nitrite of Type 2 copper. In the presence of nitrite the mutant H287E showed no evidence for the loss of water protons and no diminished ligand histidine covalency. H287E has vastly diminished activity (prior paper), and the ENDOR information is that NO2- does not bind to Type 2 copper of H287E. In summary, the electronic information from this study of native and suitably chosen mutants provided a test of the highest occupied molecular orbital (HOMO) wave function at Type 1 and Type 2 coppers and an intimate electronic insight into functional enzymatic properties.

Copper↗
PubMed2004

Filter versus wrapper gene selection approaches in DNA microarray domains.

DNA microarray experiments generating thousands of gene expression measurements, are used to collect information from tissue and cell samples regarding gene expression differences that could be useful for diagnosis disease, distinction of the specific tumor type, etc. One important application of gene expression microarray data is the classification of samples into known categories. As DNA microarray technology measures the gene expression en masse, this has resulted in data with the number of features (genes) far exceeding the number of samples. As the predictive accuracy of supervised classifiers that try to discriminate between the classes of the problem decays with the existence of irrelevant and redundant features, the necessity of a dimensionality reduction process is essential. We propose the application of a gene selection process, which also enables the biology researcher to focus on promising gene candidates that actively contribute to classification in these large scale microarrays. Two basic approaches for feature selection appear in machine learning and pattern recognition literature: the filter and wrapper techniques. Filter procedures are used in most of the works in the area of DNA microarrays. In this work, a comparison between a group of different filter metrics and a wrapper sequential search procedure is carried out. The comparison is performed in two well-known DNA microarray datasets by the use of four classic supervised classifiers. The study is carried out over the original-continuous and three-intervals discretized gene expression data. While two well-known filter metrics are proposed for continuous data, four classic filter measures are used over discretized data. The same wrapper approach is used for both continuous and discretized data. The application of filter and wrapper gene selection procedures leads to considerably better accuracy results in comparison to the non-gene selection approach, coupled with interesting and notable dimensionality reductions. Although the wrapper approach mainly shows a more accurate behavior than filter metrics, this improvement is coupled with considerable computer-load necessities. We note that most of the genes selected by proposed filter and wrapper procedures in discrete and continuous microarray data appear in the lists of relevant-informative genes detected by previous studies over these datasets. The aim of this work is to make contributions in the field of the gene selection task in DNA microarray datasets. By an extensive comparison with more popular filter techniques, we would like to make contributions in the expansion and study of the wrapper approach in this type of domains.

Artificial Intelligence↗
PubMed1993

Focal attention produces spatially selective processing in visual cortical areas V1, V2, and V4 in the presence of competing stimuli.

1. The activity of single neurons was recorded in Macaca mulatta monkeys while they performed tasks requiring them to select a cued stimulus from an array of three to eight stimuli and report the orientation of that stimulus. Stimuli were presented in a circular array centered on the fixation target and scaled to place a single stimulus element within the receptive field of the neuron under study. The timing of the cuing event permitted the directing of visual attention to the spatial location of the correct stimulus before its presentation. 2. The effects of focal attention were examined in cortical visual areas V1, V2, and V4, where a total of 672 neurons were isolated with complete studies obtained for 94 V1, 74 V2, and 74 V4 neurons with receptive-field center eccentricities in the range 1.8-8 degrees. Under certain conditions, directed focal attention results in changes in the response of V1, V2, and V4 neurons to otherwise identical stimuli at spatially specific locations. 3. More than one-third of the neurons in each area displayed differential sensitivity when attention was directed toward versus away from the spatial location of the receptive field just before and during stimulus presentation. Both relative increases and decreases in neural activity were observed in association with attention directed at receptive-field stimuli. 4. The presence of multiple competing stimuli in the visual field was a major factor determining the presence or absence of differential sensitivity. About two-thirds of the neurons that were differentially sensitive to the attending condition in the presence of competing stimuli were not differentially sensitive when single stimuli were presented in control studies. For V1 and V2 neurons the presence of only a few (3-4) competing stimuli was sufficient for a majority of the neurons studied; a majority of the V4 neurons required six to eight stimuli in the array before significant differences between attending conditions occurred. 5. For V1 and V2 neurons the neuronal sensitivity differences between attending conditions were observed primarily at or near the peak of the orientation tuning sensitivity for each neuron; the differences were evident over a broader range of orientations in V4 neurons. 6. In conclusion, neural correlates of focal attentive processes can be observed in visual cortical processing in areas V1 and V2 as well as area V4 under conditions that require stimulus feature analysis and selective spatial processing within a field of competing stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

[Selection of therapeutic procedures according to the clinicopathological features of breast cancer].

The therapeutic guidelines for breast cancer do not depend on histological type, by which prognosis can differ according to minor variations. Treatment for breast cancer is subdivided into two categories; one is for primary breast cancer which is curable by surgery and the other is for advanced or recurrent breast cancer. In the former category, the surgical method and adjuvant therapy are selected according to stage. In the latter, endocrine therapy, chemotherapy, immunotherapy and radiotherapy are indicated in single or combined use. Main factors of selection in such cases are menopausal status, estrogen receptor status and site of distant metastasis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A CAD system for the automatic detection of clustered microcalcifications in digitized mammogram films.

Clusters of microcalcifications in mammograms are an important early sign of breast cancer. This paper presents a computer-aided diagnosis (CAD) system for the automatic detection of clustered microcalcifications in digitized mammograms. The proposed system consists of two main steps. First, potential microcalcification pixels in the mammograms are segmented out by using mixed features consisting of wavelet features and gray level statistical features, and labeled into potential individual microcalcification objects by their spatial connectivity. Second, individual microcalcifications are detected by using a set of 31 features extracted from the potential individual microcalcification objects. The discriminatory power of these features is analyzed using general regression neural networks via sequential forward and sequential backward selection methods. The classifiers used in these two steps are both multilayer feedforward neural networks. The method is applied to a database of 40 mammograms (Nijmegen database) containing 105 clusters of microcalcifications. A free-response operating characteristics (FROC) curve is used to evaluate the performance. Results show that the proposed system gives quite satisfactory detection performance. In particular, a 90% mean true positive detection rate is achieved at the cost of 0.5 false positive per image when mixed features are used in the first step and 15 features selected by the sequential backward selection method are used in the second step. However, we must be cautious when interpreting the results, since the 20 training samples are also used in the testing step.

Breast Neoplasms↗
PubMed2005

pdbFun: mass selection and fast comparison of annotated PDB residues.

pdbFun (http://pdbfun.uniroma2.it) is a web server for structural and functional analysis of proteins at the residue level. pdbFun gives fast access to the whole Protein Data Bank (PDB) organized as a database of annotated residues. The available data (features) range from solvent exposure to ligand binding ability, location in a protein cavity, secondary structure, residue type, sequence functional pattern, protein domain and catalytic activity. Users can select any residue subset (even including any number of PDB structures) by combining the available features. Selections can be used as probe and target in multiple structure comparison searches. For example a search could involve, as a query, all solvent-exposed, hydrophylic residues that are not in alpha-helices and are involved in nucleotide binding. Possible examples of targets are represented by another selection, a single structure or a dataset composed of many structures. The output is a list of aligned structural matches offered in tabular and also graphical format.

Algorithms↗
PubMed1992

Clinical determinants for the management of thyroid nodules by fine-needle aspiration cytology.

To evaluate the utility of clinical features for the selection of patients with thyroid lesions suitable for diagnosis by fine-needle aspiration cytologic study, we reviewed 149 cases with complete clinical histories, laboratory evaluations, fine-needle aspirates, and histologic study of the index lesion. Review of these data demonstrated that only the presence of lymphadenopathy was of statistical value in the distinction of benign from malignant nodules. Moreover, once an aspiration diagnosis of "follicular neoplasm" had been made, no clinical, radiologic, or laboratory test aided in the distinction of follicular adenoma from follicular carcinoma.

Analysis of Variance↗
PubMed1996

Noncytotoxic alkyl-lysophospholipid treatment increases sensitivity of leukemic K562 cells to lysis by natural killer (NK) cells.

Alkyl-lysophospholipids (ALP) are a group of anti-cancer compounds tha t have previously been shown to have the unique feature of being selectively toxic to neoplastic tissues. Because alkyl-lysophospholipids target the cell membrane as their site of action, our aim was to analyse the immunological effects of a nonlethal ALP treatment on leukemic K562 cells. In this in vitro study we used ET-18-OCH3, one of the most potent ALP derivatives, at different concentrations ranging from 25 up to 100 microgram/ml. By measurement of cell viability and of apoptosis, we determined a concentration of 25 microgram/ml ET-18-OCH3 and an incubation period of 2 hr as nonlethal for K562 cells; higher concentrations markedly reduced cell viability and led to induction of apoptosis. Similar to the effects induced by nonlethal heat shock, a nontoxic ET-18-OCH3 treatment led to a significant increase in the sensitivity of K562 cells to lysis by interleukin-2 (IL-2) stimulated natural killer (NK) cells. With respect to these results, we investigated the influence of nonlethal ALP treatment on the cell surface expression patterns and compared it to the results obtained with nonlethal heat shock. ALP treatment does not induce major histocompatibility complex (MHC) expression; however, a significant increase in the cell surface expression of HSP72 was shown by immunoblot analysis of membrane lysates of either untreated or ET-18-OCH3 treated K562 cells. The increased sensitivity of ET-18-OCH3 treated K562 cells to lysis by NK cells could be correlated with the elevated cell surface expression of HSP72.

Antineoplastic Agents↗
PubMed2002

On-chip enzymatic assays.

This article reviews different possibilities for conducting enzymatic assays on microchip platforms, along with potential advantages, limitations, and selected examples of such biochips. Enzyme-based chips combine the analytical power and reagent economy of microfluidic devices with the selectivity and amplification features of biocatalytic reactions. "Lab-on-chip" devices thus allow enzymatic assays to be performed more rapidly, easily, and economically. Such assays usually rely on on-chip mixing and reactions (of the substrates and enzymes) in connection to separations (of the substrates or products). The realization of on-chip enzymatic assays thus requires understanding of how enzymatic reactions behave on a small scale and can be interfaced with separation microchips, and how the microfluidics can be tailored to suit the requirements of particular enzymatic assays. The goal is to obtain sufficient reaction times, without compromising the quality of the analytical separation. The versatility of such on-chip enzymatic assays offers great promise for decentralized testing of clinically or environmentally important substrates.

Electrophoresis, Capillary↗
PubMed1990

Differing patterns of striatal 18F-dopa uptake in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Bacterial ion channels and their eukaryotic homologues.

Due to the relative ease of obtaining their crystal structures, bacterial ion channels provide a unique opportunity to analyse structure and function of their eukaryotic homologues. This review describes prokaryotic channels whose structures have been determined. These channels are KcsA, a bacterial homologue of eukaryotic potassium channels, MscL, a bacterial mechanosensitive ion channel and ClC0, a prokaryotic homologue of the eukaryotic ClC family of anion-selective channels. General features of their structure and function are described with a special emphasis on the advantages that these channels offer for understanding the properties of their eukaryotic homologues. We present amino-acid sequences of eukaryotic proteins related in their primary sequences to bacterial mechanosensitive channels. The usefulness of bacterial mechanosensitive channels for the studies on general principles of mechanosensation is discussed.

Amino Acid Sequence↗
PubMed2004

Retrospective image-based gating of intracoronary ultrasound images for improved quantitative analysis: the intelligate method.

Quantitative analysis of intracoronary ultrasound (ICUS) studies is performed on a series of tomographic cross-sectional ICUS images acquired during a motorized 0.5 mm/sec catheter pullback. Catheter displacement in the vascular lumen during the cardiac cycle causes an anatomically shuffled ICUS study, which results in a sawtooth-shaped appearance of the coronary segment in longitudinal reconstructed views in quantitative coronary ultrasound software packages. This hampers contour detection and leads to a laborious time-consuming semiquantitative analysis process that may produce inaccurate results. To solve these problems, in the past, online ECG-gated acquisition hardware has been applied. This article describes a novel image-based gating method called Intelligate, which features automatic retrospective selection of end-diastolic frames from videotaped or digitally stored ICUS studies. Our evaluation shows that there are no quantitative differences between analysis results of hardware ECG-gated and Intelligated ICUS studies.

Coronary Circulation↗
PubMed1988

Fine structure of larval malpighian tubules and rectal sac in the tick Ornithodoros (Pavlovskyella) erraticus (Ixodoidea: Argasidae).

The fine structure of the Malpighian tubules (Mts) and rectal sac (rs) is described in the larval tick Ornithodoros (Pavlovskyella) erraticus before and after feeding up to molting. Mts consist of structurally different pyramidal and cuboidal cells along the entire length of the tubule. In unfed ticks, the two types of cell are characterized by apical microvilli and a few basal membrane infoldings. The abundant pyramidal cells contain glycogen particles, lipid droplets, lysosomelike structures, and rickettsialike microorganisms. After feeding but before molting, pyramidal cells loose glycogen particles and become very dense and dramatically reduced in size. These cells are possibly involved in the formation of guanine crystalloids as an excretory product. In contrast, cuboidal cells, filled with glycogen particles, free ribosomes, and mitochondria in unfed larvae, grow steadily after feeding; their cytoplasm becomes rich in lipid droplets in addition to showing an increase in glycogen particles. Lipid and glycogen could be the source of energy required for water and ion reabsorption in which cuboidal cells are probably involved. The paired-lobe rs consists of one type of cuboidal cells with basal membrane infoldings and a brush-border microvilli covered by a fuzzy coat of glycocalyx. These cells grow rapidly after feeding; they have functional features indicating extensive, selective reabsorption of essential components from excretory products.

Animals↗
PubMed1998

The mechanical effectiveness of erect and "bent-hip, bent-knee" bipedal walking in Australopithecus afarensis.

It is universally accepted that the postcranial skeleton of the early hominid Australopithecus afarensis shows adaptations, or at least exaptations, towards bipedalism. However, there continues to be a debate concerning the likely form of terrestrial bipedality: whether gait was erect, like our own, or "bent-hip, bent-knee" like the bipedalism of living chimpanzees. In this study we use predictive dynamic modelling to assess the mechanical effectiveness of AL-288-1 under both hypotheses, on the basis of data on segment proportions from the literature. AL-288-1's proportions are incompatible with the kinematics of chimpanzee bipedalism, but compatible with the kinematics of either erect or "bent-hip, bent-knee" human gait. In the latter case, neither the ankle nor the knee joint would have contributed substantial mechanical work to propulsion of the body, and net energy absorption is predicted for these joints, which would have resulted in increased heat load. Such an ineffective gait is unlikely to have lead to selection for "bipedal" features in the postcranial skeleton.

Animals↗
PubMed1984

A model for generalization and specification by single neurons.

A rule for environmentally dependent modification of the neuronal state is examined. Under the rule, the neuron selects a trigger feature that matches either a particular pattern in the stimulus set, or the most common pattern component, depending on a certain parameter. Thus a neuron may evolve to respond to its stimulus environment in one of two capacities, namely specification or generalization. Neurons of the former variety are labelled "S-cells"; and those of the latter, "G-cells". In the model, synaptic modification is modulated by two postsynaptic mechanisms which act antagonistically to strengthen or weaken the synaptic connectivities. The functional dependence of these mechanisms on the postsynaptic activity is shown to determine whether the neuron acts as an S-cell or a G-cell. A circuit is proposed for a module that consists of a G-cell and several S-cells sharing a common set of inputs. By inhibiting the G-cells, the S-cell acts as a contrast-enhancing element, increasing their specificities for individual patterns in the stimulus set. The output from the module is a recoded representation of the environment with respect to its general and distinctive features.

Environment↗