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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↗
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↗
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↗
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↗
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↗
PubMed1975

Ultrasonic and radionuclide scanning in pancreatic disease.

Ultrasonic examination of the pancreas is rendered difficult by the echogenic characteristics of the organ, by its depth, by the overlying gas, and by bony structures and anatomic variations. The reintroduction of gray-scale imaging promises to simplify the technique and expand its usefulness. The 75Se-/-selenomethionine scan is a reliable test when performed after effective pancreatic stimulation with a scintillation camera that permits the angulation required to separate pancreas from liver. Gallium-67-citrate may be important for both mapping inflammatory processes and imaging some tumors. Retrograde pancreatography has developed into a rather reliable and sensitive method of visualizing pancreatic duct abnormalities. Angiography remains the most reliable technique for finding small lesions, while computerized axial tomography appears a promising modality in the near future. In acute pancreatitis, gallium scanning may find a place alongside plain films, GI series, and echography. Chronic pancreatitis appears best studied by pancreatography, possibly with selenomethionine scanning as a function study and echography to find associated mass lesions. Pseudocysts are most easily located by ultrasound examination. Screening for pancreatic carcinoma is done most effectively with selenomethionine scanning when the index of suspicion is low and with pancreatography or arteriography when it is high. Echography is useful for localization for aspiration biopsy and for sequential evaluation of therapeutic response. Islet-cell tumors are best found by angiographic studies.

Acute Disease↗
PubMed1976

Subsite mapping of enzymes: collecting and processing experimental data--a case study of an amylase-malto-oligosaccharide system.

Two research groups have independently developed the theory and experimental methodology for quantitatively assessing substrate monomer-subsite binding-energies for depolymerases. When the two approaches are applied to the same enzyme-substrate system they yield surprisingly divergent results. This paper outlines the application of the two approaches to an amylase-maltooligosaccharide system and points out the more important areas of disagreement. We show that by proper data-management, the conflicts between the tow laboratories are basically resolved. The complexities of the subsite model demand extensive data-gathering and exacting data-processing and verification that the computed model-parameters can faithfully reproduce the experimental data.

Amylases↗
PubMed1998

Neural correlates of visual and motor decision processes.

Recent research has clarified and revealed characteristics of perceptual and motor decision processes in the brain. A democracy of sensory neurons discriminate the properties of a stimulus, while competition contrasts the attributes of stimuli across the visual field to locate conspicuous stimuli. Salience and significance are weighed to select an object on which to focus attention and action. Experimentally combining neural and mental chronometry has determined the contribution of perceptual and motor processes to the duration and variability of behavioral reaction time. Whereas perceptual processing occupies a relatively constant amount of time for a given stimulus condition, the processes of mapping particular stimuli onto the appropriate behavior and preparing the motor response provide flexibility but introduce delay and variability in reaction time.

Animals↗
PubMed1988

Understanding the central processing limit in consistent-mapping visual search tasks.

Effects of load (i.e., the number of stimuli in the display) have been observed in multiple-frame studies using a consistent mapping of stimuli to responses (e.g., Fisher, 1982, 1984). In a series of four experiments, it is shown that these effects are not the consequence of differences across the high- and low-load conditions in either decision noise or peripheral masking. Additionally, it is shown that of two modes of limited capacity (a limited-channel and divided-capacity model) considered as possible explanations of load effects in tasks where subjects are required to locate a target, only one--the limited-channel model--is consistent with the results from all three location tasks. Finally, it is argued that the limited-channel model predicts not only the behavior observed in the four consistent-mapping experiments reported in this article but also the behavior observed in several related consistent-mapping tasks (Kleiss & Lane, 1986; Shiffrin & Gardner, 1972).

Attention↗
PubMed2026

Radiomics as a spatial context for treatment decision-making in head and neck cancer.

Radiomics has been widely explored as a non-invasive biomarker in head and neck squamous cell carcinoma (HNSCC), yet its clinical role remains unclear. Tissue-based biomarkers differ in their susceptibility to spatial sampling. Biomarkers such as PD-L1 expression, immune-cell infiltration, necrosis, and immune exclusion may exhibit substantial spatial heterogeneity, whereas HPV/p16 status and some genomic alterations are generally more stable across the tumor. Nevertheless, localized sampling may incompletely capture heterogeneity in selected clinical contexts. This mismatch becomes clinically relevant when treatment decisions, particularly for chemoradiotherapy, immunotherapy, or de-escalation, are based on potentially non-representative biopsy findings. In this narrative review, we argue that the role of radiomics is not to outperform established biomarkers, but to contextualize them by capturing spatial heterogeneity related to hypoxia, necrosis, stromal architecture, and immune exclusion. We synthesize current evidence linking radiomic features to these biological processes and map them to specific clinical decision points, including larynx preservation, immunotherapy stratification, and recurrence assessment. Rather than serving as a standalone predictor, radiomics may provide complementary spatial information that helps identify situations in which biopsy-derived biomarkers should be interpreted with caution. Although current evidence is largely retrospective, radiomics offers a pragmatic framework for integrating spatial information into biomarker-guided clinical workflows.

Journal Article↗
PubMed1998

The genetic analysis of cancer.

During the past two decades an overwhelming amount of knowledge has been acquired on the molecular genetics of human cancer. It is now evident that cancer is essentially a genetic disease, arising from inherited and/or somatically acquired mutations at different genetic loci, and that tumourigenesis is a multistep process. Gene mapping studies of inherited cancer syndromes have resulted in the identification of many genes implicated in the initiation of tumours. Importantly, alterations of the same genes were also found to play a role in the development of common, non-familial tumours. The genes involved belong to distinct functional classes, and include proto-oncogenes and tumour suppressor genes, which are regulators of cellular growth and proliferation, cell adhesion and programmed cell death. Another class of cancer susceptibility genes consists of DNA repair genes, which are involved in maintaining genomic stability. In unravelling the genetic basis of cancer, the localization and identification of genes involved in tumourigenesis can be considered as the 'easy' part; determination of the normal physiological function of these genes and their precise role in tumourigenesis has proved to be much more difficult. In this review, we highlight some of the major breakthroughs in the field of cancer genetics, and discuss recent insights in the putative role of proto-oncogenes, tumour suppressor genes and DNA repair genes in the initiation and progression of cancer. Also, we point to some of the challenges to be faced in the coming years.

DNA, Neoplasm↗
PubMed1992

The locus of repetition priming of spoken word production.

Naming of a pictured object is substantially facilitated when the name has recently been produced in response to a definition or read aloud. The first experiment shows this to be so when over one hundred trials have intervened, and when the subjects can name the pictures quickly and accurately in the absence of priming. The locus of the effect must be in lexicalization processes subsequent to picture identification and is unlikely to be mediated by recovery of an episodic trace. Two further experiments show that prior production of a homophone of the object's name is not an effective prime, (although slower responses are somewhat facilitated when the homophones are spelled the same). Hence the facilitation observed for repeated production of the same word cannot be associated with the repetition of the phonological form per se. We conclude that the facilitation must be associated with retrieval of the semantic specification or the process of mapping of that specification to its associated phonological representation.

Adolescent↗
PubMedDate not supplied

Organizational re-engineering using systems modelling: rediscovering the physics of the health service.

This paper explores the general role of systems modelling and its specific use in the UK National Health Service for providing a balanced overview of change management which links organizational structure, strategy, and process. The maps and modelling tools of the method are described, together with an outline of how they can be used to simulate and test alternative interventions in complex organizations and to create a management focus on generic insights, accelerated business learning, and improved financial performance. A case study involving the use of systems modelling at the interface between the health service and community care is presented as a specific example of the method in action.

Community Health Services↗