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PubMedDate not supplied

Low-dimensional chaos maps learning in a model neuropil (olfactory bulb).

Quantification of a chaotic system can be made by calculating the correlation dimension (D2) of the data that the system generates (Packard et al., 1980). The D2 algorithm, however, requires stationarity of the generator, a feature that biological data rarely reflect (Mayer-Kress et al., 1988). So we developed the "point correlation dimension" (PD2), an algorithm that accurately tracks D2 in linked data of different dimensions (Carpeggiani et al., 1991). We now present a mathematical argument that, for stationary data, individual PD2s converge to D2 and we demonstrate that the algorithm rejects contributions made by bursts of noise. Data were obtained from the surface of the olfactory bulb of the conscious rabbit (64 electrodes, 640 Hz each, 1.3 sec epochs) before and after presentation of a novel or habituated odor. D2 could be calculated in only 1 of 10 novel-odor trials, whereas PD2 could be calculated in all. Both algorithms indicated that a novel odor evokes a spatially uniform dimensional increase. The PD2 uniquely exhibited the dimensional decreases that occur during inspiration and the gradients of mean dimension present during the nonstimulated control state. These control gradients remained unchanged without odor experience, but showed spatially specific PD2 increases following odor habituation. It is interpreted that, 1) the PD2 is sensitive, accurate, and appropriate for dimensional assessment of biological data, 2) that during analysis of unfamiliar information a single global process is transiently evoked in the neuropil, and 3) after experience multiple spatially specific processes tonically map the sites of learning.

Algorithms↗
PubMedDate not supplied

Basic level object categories support the acquisition of novel adjectives: evidence from preschool-aged children.

Two experiments examined 3- and 4-year-old children's ability to map novel adjectives to object properties. Sixty-four children were introduced to a target (e.g., a bumpy object), and asked to choose between (1) a matching test object (e.g., a different bumpy object), and (2) a contrasting test object (e.g., a smooth object). Four-year-olds successfully extended novel adjectives from the target to the matching test object whether these objects were drawn from the same, or different, basic level categories. In contrast, 3-year-olds' extensions were more restricted. They successfully extended novel adjectives if the target and test objects were drawn from the same basic level category but failed to do so if the objects were drawn from different basic level categories (Experiment 1). However, if 3-year-olds (n = 20) were first permitted to extend a novel adjective to objects within the same basic level category, they were subsequently able to extend that novel adjective broadly to objects from different basic level categories (Experiment 2). Thus, basic level object categories serve as an initial foundation in the process of mapping novel adjectives to object properties.

Child Language↗
PubMed2000

Structure and mutation analysis of the gene encoding DNA fragmentation factor 40 (caspase-activated nuclease), a candidate neuroblastoma tumour suppressor gene.

We have characterised the DFFB gene, encoding the active subunit of the apoptotic nuclease DNA fragmentation factor (DFF40). DFFB maps to 1p36, near the imprinted putative tumour suppressor gene TP73. The DFFA gene (encoding the inhibitory DFF45 subunit) also maps to 1p36.2-36.3, and we show by FISH that DFFB lies distal to DFFA. We have also mapped a processed DFFB pseudogene to chromosome 9. DFFB itself has seven coding exons spanning 10 kb. Exhaustive mutation screening of 41 neuroblastomas and other tumours in which a 1p36 tumour suppressor gene is implicated showed no tumour-specific mutations. A coding region polymorphism was used to demonstrate uniformly biallelic expression in human fetal DFFB transcripts. Since the putative neuroblastoma tumour suppressor gene in distal 1p36 is predicted to be maternally expressed, the lack of imprinting and absence of somatic mutations in DFFB indicate that it is probably not the neuroblastoma tumour suppressor gene.

Apoptosis↗
PubMed2001

The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.

Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (massive repeat units) using an iterative mapping-sequencing process. A complex of three palindromes, the largest spanning 3 Mb with 99.97% identity between its arms, encompasses the AZFc region. The palindromes are constructed from six distinct families of amplicons, with unit lengths of 115-678 kb, and may have resulted from tandem duplication and inversion during primate evolution. The palindromic complex contains 11 families of transcription units, all expressed in testis. Deletions of AZFc that cause infertility are remarkably uniform, spanning a 3.5-Mb segment and bounded by 229-kb direct repeats that probably served as substrates for homologous recombination.

Base Sequence↗
PubMed1993

The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random.

The dynamic periphery of unstimulated, preaggregation, hunger-stage Dictyostelium discoideum amoebae was investigated by time-lapse videomicroscopy and digital image processing. Circular maps (i.e. of each of 360 radii around the cell transformed upon Cartesian coordinates) were constructed around the centroid of individual cell images and analysed in time series. This novel technique generated spatiotemporal structures of various degrees of order in the maps, which resemble classical wave interference patterns. The patterns thus demonstrate that cell movement is not random and that cells are intrinsically vibrating bodies, transited by self-organized, superpositioned, harmonic modes of rotating oscillatory waves (ROWS). These waves appear to depend upon spatiotemporal oscillations in the physicochemical reactions associated with actin polymerization, and they govern pseudopodial movements, cell shape and locomotion generally. ROWS in this case are unrelated to the cyclic-AMP-regulated oscillations, which characterize later, aggregative populations of Dictyostelium. However, the exposure of aggregation-stage cells to a pulse of the chemoattractant cyclic-AMP induces a characteristic sequence of changes in the global cellular concentration and spatiotemporal distribution of fibrillar (F-)actin. This reaction begins with what appears to be a phase resetting of ROWS and it may, therefore, underlie the cellular perception of and response to chemotactic signals. We also develop here an analytical mathematical description of ROWS, and use it to simulate cell movements accurately.

Actins↗
PubMed1996

Differential temporal evolution of post-training changes in regional brain glucose metabolism induced by repeated spatial discrimination training in mice: visualization of the memory consolidation process?

The present study analyses the effects of the stage of learning on the spatial patterns and time-course of [14C]glucose uptake in BALB/c mice brain regions produced by spatial discrimination training in an eight-arm radial maze. Our particular approach was designed to follow, during the post-training period, the level of functional activity in individual brain areas which may underlie the memory consolidation process. Regional mapping of relative [14C]glucose uptake was assessed at three post-training time intervals (5 min, 1 and 3 h) after either the first (Day 1), the fourth (Day 4) or the last (Day 9) daily training session of the discrimination task and compared with sham-conditioned animals placed in the same experimental environment. The results indicated that numerous subcortical and cortical brain regions exhibit metabolic alterations following the acquisition of the spatial discrimination task. These alterations, which were specifically related to learning since they did not appear in sham-conditioned animals, were functions both of the post-training interval studied and of the degree of mastery of the task. On Day 1, a progressive, time-dependent and sequential increase in labelling was found from subcortical (5 min post-training) to cortical regions (3 h post-training). On Day 4, a peak of cortical metabolic activation was identified at 1 h post-training. In contrast, on Day 9, maximum labelling was found 5 min post-training in all subcortical and cortical regions followed by a general monotonic decline at 1 and 3 h post-training. These findings, which show widely distributed changes of metabolic activity in the brain, are consistent with the hypothesis that learning involves distributed neural networks. The sequential activation from subcortical to cortical regions seems to indicate a general mechanism whose function would ultimately be to store cortical memory representations. The acquisition-dependent shifts in the patterns of post-training metabolic labelling observed as a function of task mastery may be taken to represent a visualization of the spatio-temporal evolution of the networks of brain structures actively engaged in the memory consolidation process. In particular, the present data suggest that the duration of post-acquisition memory processing is a function of the quantity of new information which has to be dealt with by the central nervous system.

Animals↗
PubMedDate not supplied

The service blueprint as a tool for designing innovative pharmaceutical services.

OBJECTIVE: To describe service blueprints, discuss their need and design, and provide examples of their use in advancing pharmaceutical care. BACKGROUND: Service blueprints are pictures or maps of service processes that permit the people involved in designing, providing, managing, and using the service to better understand them and deal with them objectively. A service blueprint simultaneously depicts the service process and the roles of consumers, service providers, and supporting services. Service blueprints can be useful in pharmacy because many of the obstacles to pharmaceutical care are a result of insufficient planning by service designers and/or poor communication between those designing services and those implementing them. One consequence of this poor design and communication is that many consumers and third party payers are uninformed about pharmacist roles. Service blueprints can be used by pharmacists to promote the value of pharmaceutical care to consumers and other decision makers. They can also assist in designing better pharmaceutical services. METHODS: Blueprints are designed by identifying and mapping a process from the consumer's point of view, mapping employee actions and support activities, and adding visible evidence of service at each consumer action step. Key components of service blueprints are consumer actions, "onstage" and "backstage" employee actions, and support processes. DISCUSSION: Blueprints can help pharmacy managers identify and correct problems with the service process, provide pharmacy employees an opportunity to offer feedback in the planning stages of services, and demonstrate the value of pharmaceutical services to consumers. CONCLUSION: Service blueprints can be a valuable tool for designing, implementing, and evaluating pharmacy services.

Communication↗
PubMed2000

Is keratoconus a true ectasia? An evaluation of corneal surface area.

BACKGROUND: Keratoconus has long been considered to be an ectasia produced by stromal stretching. Although stretching should result in increased corneal surface area, previous observations of topography during progression of keratoconus have suggested that surface area may actually be conserved. A novel objective surface area measurement based on corneal topography was tested and applied to data from actual corneas under various conditions for comparative analysis. SETTING: The LSU Eye Center clinic videokeratography archives. METHODS: TMS-1 videokeratography files (Tomey Corp, Cambridge, Mass) were obtained from 6 groups of corneas: normal (n = 29), keratoconus from mild to severe states (n = 51), topographically judged keratoconus-suspect conditions (n = 10), postoperative photorefractive keratectomy for myopia (n = 39), with-the-rule corneal astigmatism (n = 17), and keratoglobus (n = 1). Additionally, 3 different spherical test surfaces were analyzed to verify the accuracy of the process. Only maps with no missing data out to ring 29 were used. The cumulative surface area from center to periphery was determined by calculating and summing the area of individual patches along consecutive annular rings. Mean surface area with respect to mean chord radius was plotted for each corneal condition, and curve fitting was used to extend each result to a 5. 85-mm limbus. Means, SEs, and 95% confidence intervals were calculated at intervals for statistical comparisons among all groups. Computer-generated surfaces helped to evaluate the relationship between shape and surface area. RESULTS: When videokeratographic test targets were used, surface area error was less than 2%, which was deemed acceptable. Normal corneas had a mean +/- SE surface area of 120.3 +/- 2.2 mm(2), whereas all keratoconus corneas combined had a mean +/- SE surface area of 116.2 +/- 3.4 mm(2). The difference was not significant at any chord radius (analysis of variance, P<. 05). The keratoglobus cornea was found to have a surface area of 129. 9 mm(2), which was 7.98% greater than normal. An individual with progressive keratoconus exhibited no appreciable trend toward increasing surface area during a 76-month period. The corneas in the other groups resembled normal corneas in their total surface area. CONCLUSIONS: With the exception of the single case of keratoglobus, corneal surface area tended to be conserved near a value of 120 mm(2) for all groups in the study, including corneas with keratoconus. Surface area is remarkably insensitive to curvature change near the vertex. Flattening seen in the periphery of corneas with keratoconus suggests that biomechanical coupling compensates for any increase in curvature occurring in the region of the cone itself. Thus, it seems that keratoconus is not a true ectasia as is keratoglobus, but rather a specialized type of warpage, at least in mild to moderate forms of the disease. Arch Ophthalmol. 2000;118:1179-1186

Algorithms↗
PubMed1985

Gene duplications in the TL region of the mouse major histocompatibility complex.

We have isolated a class I gene from the TL region of the A/J mouse. The gene, T2A, is a homologue of the C57BL/10 mouse gene T2. In the process of mapping this gene we screened a number of BALB/c class I cosmid clusters with a T2A flanking probe. Several of the hybridizing clusters were found to contain identical DNA segments and could therefore be linked together into one single BALB/c TL region which appears to be identical to the TL region of the C57BL/10 mouse. However, two of the hybridizing clusters do not overlap with the C57BL/10 TL region. It appears that these two clusters represent a partial duplication of the TL region in the BALB/c mouse.

Animals↗
PubMed1995

Identification of a regulatory motif in Hsp70 that affects ATPase activity, substrate binding and interaction with HDJ-1.

The Hsp70 family of molecular chaperones has an essential role in the synthesis, folding and translocation of the nascent peptide chain. While the general features of these activities are well documented, less is understood about the regulation of these activities. The ATPase rate is stimulated by non-native proteins, furthermore, interaction with ATP leads to the release of protein substrate concurrent with a conformational change in Hsp70. One interpretation of these data is that the two domains of Hsp70 interact. In the process of mapping the carboxyl-terminal boundary of the substrate binding domain for human Hsp70, we identified a regulatory motif, EEVD, which is conserved at the extreme carboxyl terminus among nearly all cloned cytosolic eukaryotic Hsp70s. Deletion or mutation of EEVD affects the ATPase activity, the ability to interact with substrates, and interferes with the ability of the mutant Hsp70 to interact with HDJ-1 in the refolding of denatured firefly luciferase. Examination of the biophysical properties of the mutant Hsp70s reveals a change in the overall shape and conformation of the protein consistent with reduced interactions between the two domains. These data suggest that the EEVD motif is involved in the intramolecular regulation of Hsp70 function and intermolecular interactions with HDJ-1.

Adenosine Triphosphatases↗
PubMed2000

Role of Mimeticism and Spatiality in Textual Recall.

Four experiments were conducted to investigate the role of map spatiality and icon mimeticism in facilitating text recall. A secondary goal was to explore an assumption of the conjoint retention hypothesis, that the visuospatial component of working memory is involved in retrieving map information. We manipulated display conditions to evaluate the separate and combined effects of map spatiality and icon mimeticism on text recall. We also utilized a concurrent task paradigm to assess both the recognition of spatial displays and the recall of map feature information. The results of all four experiments point to the mimeticism of icons as the key attribute of maps for facilitating recall, rather than the spatial layout of the map when visual displays and text are presented simultaneously during encoding. We also found no evidence indicating that maps are processed in a more spatial manner than are lists. Copyright 2000 Academic Press.

Journal Article↗
PubMed2001

In vitro translational analysis of genomic, defective, and satellite RNAs of Cryphonectria hypovirus 3-GH2.

Cryphonectria hypovirus 3-GH2 (CHV3-GH2) is a member of the fungal virus family Hypoviridae that differs from previously characterized members in having a single large open reading frame with the potential to encode a protein of 326 kDa from its 9.8-kb genome. The N-terminal portion of the ORF contains sequence motifs that are somewhat similar to papain-like proteinases identified in other hypoviruses. Translation of the ORF is predicted to release autocatalytically a 32.5-kDa protein. A defective RNA, predicted to encode a 91.6-kDa protein representing most of the N-terminal proteinase fused to the entire putative helicase domain, and two satellite RNAs, predicted to encode very small proteins, also are associated with CHV3-GH2 infected fungal cultures. We performed in vitro translation experiments to examine expression of these RNAs. Translation of three RT-PCR clones representing different lengths of the amino-terminal portion of the ORF of the genomic RNA resulted in autocatalytic release of the predicted 32.5-kDa protein. Site-directed mutagenesis was used to map the processing site between Gly(297) and Thr(298). In vitro translation of multiple independent cDNA clones of CHV3-GH2-defective RNA 2 resulted in protein products of approximately 92 kDa, predicted to be the full-length translation product, 32 kDa, predicted to represent the N-terminal proteinase, and 60 kDa, predicted to represent the C-terminal two-thirds of the full-length product. In vitro translation of cDNA clones representing satellite RNA 4 resulted in products of slightly less than 10 kDa, consistent with the predicted 9.4 kDa product.

Amino Acid Sequence↗
PubMed1985

Identification and estimation algorithm for stochastic neural system. II.

The algorithm for identifying the stochastic neural system and estimating the system process which reflects the dynamics of the neural network are presented in this paper. The analogous algorithm has been proposed in our preceding paper (Nakao et al., 1984), which was based on the randomly missed observations of a system process only. Since the previous algorithm mentioned above was subject to an unfavorable effect of consecutively missed observations, to reduce such an effect the algorithm proposed here is designed additionally to observe an intensity process in a neural spike train as the information for the estimation. The algorithm is constructed with the extended Kalman filters because it is naturally expected that a nonlinear and time variant structure is necessary for the filters to realize the observation of an intensity process by means of mapping from a system process to an intensity process. The performance of the algorithm is examined by applying it to some artificial neural systems and also to cat's visual nervous systems. The results in these applications are thought to prove the effectiveness of the algorithm proposed here and its superiority to the algorithm proposed previously.

Animals↗
PubMed1976

Distribution of cerebral degeneration in Alzheimer's disease. A clinico-pathological study.

Seven cases of Alzheimer's disease were studied in detail from a clinical and neuropathological point of view. The degenerative process was mapped with regard to regional variations in the intensity, extent and consistency of focal accentuations. The degeneration was regularly found to be most pronounced in certain areas: maximal cortical degeneration occurred in the medial temporal (limbic) area and, in the lateral hemisphere, consistently within a field expanding from the posterior inferior temporal areas to the adjoining portions of the parieto occipital lobes. In addition, the posterior cingulate gyrus was severely involved. On the other hand certain areas were notably and consistently spared or less involved, mainly the anterior cingulate gyrus and the calcarine and central sensory motor areas (primary projection areas). The frontal lobes occupied an intermediate position, being less severely involved than is usually reported. The clinical symptoms correlated well with this pattern of degeneration. Thus groups of symptoms such as memory dysfunction, emotional and personality alterations, and some symptoms of the Klüver-Bucy syndrome, were referable to the limbic lesions. The cortical lesions of the temporo-parieto-occipital association cortex correlated with the symptoms of agnosia, aphasia and apraxia, which were recorded in all cases. The relative sparing of the primary projection areas correspond well to findings of retained motility and perception even in later stages of the disease. The relative sparing of the frontal lobes and the anterior cingulate gyrus was related to the preservation of habitual personality traits. The pattern described may be related to ontogenetic features, and the tendency to focalization to the age of disease onset. The role of genetic factors and of other diseases is discussed.

Aged↗
PubMed2002

Spectrum of phenotypes and genotypes in Parkinson's disease.

The pathogenesis of Parkinsons disease (PD) is currently unknown. Environmental and genetic factors might contribute to the neurodegenerative process. Genetic mapping approaches in rare familial cases with autosomal recessive and autosomal dominant inheritance of PD suggest wide genetic heterogeneity of the disease. These gene loci in turn allow now a more specific clinical investigation of affected families to study the clinical heterogeneity of PD. The recent identification of mutations in three genes involved in protein degradation and aggregation in familial PD does now facilitate the deciphering of other genes involved in the pathogenesis of the disease.

Chromosome Mapping↗
PubMed1985

Influence of allelic polymorphism on the assembly and surface expression of class II MHC (Ia) molecules.

Cell surface Ia expression was examined following transfection of murine alpha and beta class II major histocompatibility complex (MHC) genes into L cells. Although haplotype-matched (e.g., Ak beta Ak alpha) gene pairs yielded high expression in primary transfectants, haplotype-mismatched pairs (e.g., Ak beta Ad alpha) gave unexpectedly low expression. RNA analysis revealed a requirement for greater A beta, and particularly A alpha transcript levels in haplotype-mismatched vs. haplotype-matched transfectants with similar levels of membrane Ia. A beta allelic control of this assembly/expression process was mapped to the NH2-terminal (beta 1) domain, the locus of high intraspecies polymorphism. These data on the effects of allelic variation on Ia levels provide a possible explanation for the strong linkage disequilibrium of A alpha and A beta genes and may account for the current molecular organization of the I region of the MHC.

Alleles↗
PubMed1984

The genesis of bifid T waves: experimental demonstration in isolated perfused rabbit hearts.

In an attempt to elucidate the genesis of bifid T waves, we recorded transmembrane potentials of subepicardial ventricular muscle fibers simultaneously with a bipolar ventricular electrogram in isolated, perfused rabbit hearts, and the timing of the two apices of the T wave (aT1, aT2) was correlated with ventricular repolarization. The following results were obtained. (1) In seven of the nine hearts in which the repolarization process was mapped on the anterior and posterior surfaces of both ventricles, the 80% repolarization times of the left and the right ventricles were scattered around aT1 and aT2, respectively, and their average values closely corresponded to Q-aT1 and Q-aT2 intervals. This suggested that aT1 and aT2 depended on repolarization of the left and the right ventricles, respectively. (2) In one heart, aT1 appeared to reflect repolarization of the posterior ventricular wall, and aT2 that of the anterior wall. (3) In the remaining heart, aT2 coincided with repolarization of the anterobasal portion of the right ventricle, and aT1 that of the remaining portions of the ventricles. Even when ventricular repolarization was modified by low K+, low Ca2+ or procainamide perfusion, or by premature atrial stimulation, the close temporal correlation of the left and right ventricular repolarization with the two apices of the T wave was maintained. Selective cooling of the perfusate in either the left or the right coronary artery resulted in the production of bifid T waves in which aT2 coincided with the delayed repolarization of the cooled ventricle. We conclude that either physiologically or pathologically delayed repolarization in certain portions of the ventricles is most likely the cause of bifid T waves.

Action Potentials↗