Relative Temporal Order Research Articles

Enactment encoding promotes relative temporal order memory.

Studies have shown that enactment improves memory; however, in daily life, our memories of motor events often exhibit a relative temporal order. Therefore, this study examined whether enactment promotes relative temporal order memory. In Experiment 1, a sequential recall task and a subject-performed task were used to explore whether enactment encoding improved relative temporal order memory. The results showed that the relative temporal order memory of the enactment-encoding group was significantly better than that of the verbal-encoding group, indicating that enactment promoted relative temporal order memory. Since temporal order memory is often affected by spatial cues, in Experiment 2, we further controlled spatial cues and used a 2 (spatial cues: consistent with temporal order, vs. no cues) × 2 (encoding type: verbal vs. enactment) design to explore whether spatial cues influence the effect of enactment encoding on temporal order memory. The results showed that compared with verbal encoding, enactment encoding significantly improved relative temporal order memory. However, no effect of spatial cues on relative temporal order memory was found. Our study confirmed that enactment encoding promotes relative temporal order memory performance independent of spatial cues.

Judgments of alphabetical order and mechanisms of congruity effects.

The congruity effect is a highly replicated feature of comparative judgments, and has been recently found in memory judgments of relative temporal order. Specifically, asking "Which came earlier?" versus "Which came later?" facilitates response times and sometimes error rates on judgments toward the beginning or end of the list, respectively. This suggests memory judgments of relative temporal order may be part of a broader class of comparative judgments. If so, the same congruity effect should also be found with the English alphabet, despite the alphabet being a longer, semantic-memory list, with forward directional encoding. A large-sample study (N = 340) produced a clear congruity effect in response time and even error rate (when controlled for response time). The large number of serial positions afforded by the alphabet enabled us to test a repertoire of mathematical models instantiating four distinct mechanisms of the congruity effect, against the empirical serial-position effects. The best-performing model assumed a response bias toward a discrete set of letters conceived of as "early" versus "late," respectively, an account that had previously been ruled out for typical comparative-judgment paradigms. In contrast, models implementing congruity effect mechanisms supported for conventional comparative judgment paradigms (based on reference-point theory or positional discriminability) produced quantitatively poorer fits, with more curvilinear serial-position effects that deviated from the data. The congruity effect thus extends to long, highly directional semantic-memory lists. However, qualitatively different serial-position effects across models suggest that, despite the superficial similarity, there are probably several quite different mechanisms that produce congruity effects, which may, in turn, depend on specific task characteristics. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cell and molecular transitions during efficient dedifferentiation.

Dedifferentiation is a critical response to tissue damage, yet is not well understood, even at a basic phenomenological level. Developing Dictyostelium cells undergo highly efficient dedifferentiation, completed by most cells within 24 hr. We use this rapid response to investigate the control features of dedifferentiation, combining single cell imaging with high temporal resolution transcriptomics. Gene expression during dedifferentiation was predominantly a simple reversal of developmental changes, with expression changes not following this pattern primarily associated with ribosome biogenesis. Mutation of genes induced early in dedifferentiation did not strongly perturb the reversal of development. This apparent robustness may arise from adaptability of cells: the relative temporal ordering of cell and molecular events was not absolute, suggesting cell programmes reach the same end using different mechanisms. In addition, although cells start from different fates, they rapidly converged on a single expression trajectory. These regulatory features may contribute to dedifferentiation responses during regeneration.

PPM1D and DNMT3A Mutations in Myelodysplasia and Clonal Hematopoiesis

Introduction: Age-related clonal hematopoiesis (CH) has been implicated in an increased risk of myeloid neoplasms. While common driver genes mutated in CH largely overlap to those in myeloid neoplasms, a notable exception is protein phosphatase Mg2+/Mn2+dependent 1D gene (PPM1D), encoding a p53-targeting phosphatase. Although it is known to be involved in DNA damage response pathways and more frequently mutated in therapy-related myeloid neoplasms than in primary ones, its role in CH and myeloid neoplasms has not been fully understood. Aim: To identify genetic features associated with PPM1D mutations, we examined genetic profiles in the large cohorts of healthy elderly individuals and patients with myelodysplasia. Methods: We enrolled 10,826 healthy individuals (>60y) and 1,213 cases with myelodysplasia, including myelodysplastic syndromes (MDSs), myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) (n=1,080), and secondary acute myeloid leukemia (sAML) (n=133), of which 567 cases were treated by hematopoietic stem cell transplantation (HSCT) through the Japan Marrow Donor Program just after sampling, and 332 of them underwent any therapy before sampling. Samples from healthy individuals were subjected to multiplex-amplicon sequencing for 22 genes, including PPM1D and other genes, related to CH or myeloid neoplasms. Myelodysplasia samples had previously been sequenced for major myeloid drivers, except for PPM1D, which was newly sequenced in this study. Results: Frequency of PPM1D mutations in myelodysplasia and healthy individuals was 3.1% and 0.42%, with a median variant allele frequency (VAF) of 0.043 and 0.056, respectively. PPM1D mutations were more frequent in cases with previous treatment (4.8%) than in those without known history of therapy (2.3%) (P=0.038). In MDS and MDS/MPN cases, 59.5% of PPM1D mutations had accompanying mutations, in which DNMT3A mutations were the most frequently identified (16.2%, n=6). These 6 cases were diagnosed with RCUD (n=1), RCMD (n=2), RAEB-2 (n=2), or CMML (n=1). The association between PPM1D and DNMT3A mutations was also seen in 7 of 45 healthy individuals with PPM1D mutations, of which one had a DNMT3A-R882 mutation. In the HSCT cohort, 192 cases harbored ≥2 mutations of the 22 CH-related genes, and the relative temporal order of these mutations was investigated using Bradley-Terry model relying on their tumor cell fractions. The estimate of PPM1D mutations tended to be smaller than that of DNMT3A mutations. To further confirm chronological order of these mutations, VAF values were compared between them in the individuals with concurrent PPM1D and DNMT3A mutations (n=13; 6 myeloid neoplasms and 7 healthy donors). In the combined cohort, the VAFs of PPM1D and DNMT3A mutations were correlated (Spearman; correlation coefficient=0.87, P=1.2x10e-5). In both neoplastic and healthy cohort, the VAFs of DNMT3A-R882 mutations were larger than those of accompanying PPM1D mutations. These findings suggest that these mutations should be acquired in the same cell populations and that DNMT3A mutations might occur prior to PPM1D mutations. With regard to copy number alterations associated with PPM1D-mutated myelodysplasia, del(5q) (16.7%) and complex(-like) karyotypes (13.9%) were among the most frequent chromosomal abnormalities. Approximately 65% of PPM1D-mutated tumor samples had normal karyotype, which was similar to PPM1D-unmutated cases. PPM1D mutations did not significantly influence overall survival, although PPM1D mutations tended to negatively affect clinical outcome among patients who were treated with HSCT (Hazard ratio, 1.61; 95% confidence interval, 0.95 to 2.70). Conclusion: PPM1D mutations were more enriched in myelodysplasia than in CH, and the median value of VAF in PPM1D mutations in CH was not significantly different from that in myelodysplasia. The size of PPM1D-mutated clones tended to be relatively smaller compared with that of clones with other mutations in myelodysplasia. PPM1D and DNMT3A mutations might be cooperatively associated in the pathogenesis of myelodysplasia and CH. Disclosures Baer: MLL Munich Leukemia Laboratory: Employment. Nadarajah:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Atsuta:CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria. Miyazaki:Chugai: Research Funding; Otsuka: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Dainippon-Sumitomo: Honoraria; Kyowa-Kirin: Honoraria. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Ogawa:Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding; Qiagen Corporation: Patents & Royalties; Asahi Genomics: Equity Ownership; RegCell Corporation: Equity Ownership; Kan Research Laboratory, Inc.: Consultancy; ChordiaTherapeutics, Inc.: Consultancy, Equity Ownership.

Learning attentive dynamic maps (ADMs) for Understanding Human Actions

This paper presents a novel end-to-end trainable deep architecture to learn an attentive dynamic map (ADM) for understanding human motion from skeleton data. An ADM intends not only to capture the dynamic information over the period of human motion, referred to as an action, as the conventional dynamic image/map does, but also to embed in it the spatio-temporal attention for the classification of the action. Specifically, skeleton sequences are encoded into sequences of Skeleton Joint Maps (STMs), each STM encodes both joint location (i.e. spatial) and relative temporal order (i.e. temporal) of the skeleton in the sequence. The STM sequences are fed into a customized 3DConvLSTM to explore the local and global spatio-temporal information from which a dynamic map is learned. This dynamic map is subsequently used to learn the spatio-temporal attention at each time-stamp. ADMs are then generated from the learned attention weights and all hidden states of the 3DConvLSTM and used for action classification. The proposed method achieved competitive performance compared with the state-of-the-art results on the Large Scale Combined dataset, MSRC-12 dataset and NTU RGB+D dataset.

Emergence of spike correlations in periodically forced excitable systems.

In sensory neurons the presence of noise can facilitate the detection of weak information-carrying signals, which are encoded and transmitted via correlated sequences of spikes. Here we investigate the relative temporal order in spike sequences induced by a subthreshold periodic input in the presence of white Gaussian noise. To simulate the spikes, we use the FitzHugh-Nagumo model and to investigate the output sequence of interspike intervals (ISIs), we use the symbolic method of ordinal analysis. We find different types of relative temporal order in the form of preferred ordinal patterns that depend on both the strength of the noise and the period of the input signal. We also demonstrate a resonancelike behavior, as certain periods and noise levels enhance temporal ordering in the ISI sequence, maximizing the probability of the preferred patterns. Our findings could be relevant for understanding the mechanisms underlying temporal coding, by which single sensory neurons represent in spike sequences the information about weak periodic stimuli.

A hidden ambiguity of the term "feedback" in its use as an explanatory mechanism for psychophysical visual phenomena.

Over the last decades many researchers have used concepts like “feedback,” “reentrance,” “backpropagation,” “top–down (modulation),” or “reverse hierarchy” to specify the mechanisms that underlie various visual phenomena (e.g., Di Lollo et al., 2000; Lamme and Roelfsema, 2000; Pascual-Leone and Walsh, 2001; Super et al., 2001; Ro et al., 2003; Ahissar and Hochstein, 2004; Bar et al., 2006; Fahrenfort et al., 2007; Koivisto, 2012). An incomplete list of these phenomena includes visual (object substitution) masking, shape discrimination, illusory contours, illusory motion, priming effects, etc. Empirical evidence or theoretical argumentation in favor of the suggested mechanismic explanations mainly consists in finding or postulating an association between a temporally delayed, secondary activition of lower level neural units with correct reports of target stimuli, even though the higher level neural units in the processing hierarchy were already activated earlier. On that basis, feedforward processing has been argued to be insufficient for target perception. However, in most of the studies the relative temporal order of activity at different levels alone is taken as proof of reentrant modulation without precisely measuring the neural sources of this top–down effect. In principle, it is equally possible that the source of the higher level activity from which the top–down signals are sent back to earlier feature-encoding neural units (i) is specifically linked to those features by virtue of constituting the higher level nodes associated with specific attributes of the target stimulus (thus mediating feature-binding for object integration) or (ii) is not specifically linked in this manner. In the latter case, the source of top–down modulation may be the result of the arousal or alerting boost triggered by the target stimulus via feedforward collateral activation of subcortical reticulo-thalamic units, which in turn is followed by the cortical spread of the thalamocortical activation, including the downpropagation of the non-specific wave of modulation to the early cortical areas. The non-specific system functions include arousal, attentional modulation, intercortical synchronization of neural activity, bringing the preconsciously processed specific content to awareness, “event-holding” the content in working memory, and alerting subjects to newly appearing objects and changes (Magoun, 1958; Purpura, 1970; Purpura and Schiff, 1997; Jones, 2001; Llinas and Ribary, 2001; Van der Werf et al., 2002; Ribary, 2005; Schiff et al., 2013; Saalmann, 2014). This non-specific system (NSP) targets layer-1 apical dendrites of the layer-5 and -6 pyramidal neurons. But since NSP-modulation is directed at the cortical neurons with specific representational functions, its function may go unacknowledged because the cortical units, when activated by NSP-modulation, can produce content-specific subjective effects misleading us to believe that the entire process has been specific throughout.

Absolute and relative temporal order memory for performed activities following stroke

Reconstructing the temporal order of events is a crucial part of episodic memory. The temporal dimension, however, is often discarded in clinical settings, and measurements of true temporal aspects of episodic memory are scarce. The present study assessed temporal memory in stroke patients and in age- and education-matched healthy controls. Both groups underwent a standardized neuropsychological examination. We asked participants afterwards to reconstruct the order of tests they had performed, measured in absolute temporal order (event placed on correct moment in sequence) and relative temporal order (event placed correctly relative to directly preceding and following events). The aim of the study was to examine how serial-position curve effects (measuring absolute temporal order anchored in exact time) and how relative temporal order memory (anchored to other events) may differ in a group of cerebral stroke patients. Another aim was to link temporal order memory deficits with established neuropsychological measures of cognitive functioning. Although item identification was comparable in both groups, absolute temporal order memory was impaired in patients: A total of 43% of the patients lacked the expected primacy and recency effects (serial position effect). In addition, relative temporal order memory was affected in this group as well, F(1, 70) = 4.08, p < .05; 25% of the patients were impaired in reconstructing the relative temporal order (p = .019, Fisher’s Exact Test). Both absolute and relative temporal order memory performance related to the domains of executive functioning and memory. Our results suggest that it is important to test both absolute and relative temporal order memory, especially because these types of memory depend on different anchors, either on time or on adjacent events.

Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing

AbstractDiffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention.

Notas sobre aspectos gramaticais de ordem cognitiva e discursiva

Procuramos desenvolver uma discussão sobre a relação que a linguística funcionalista mantém com a linguística cognitiva, inclusive, a ela aliando-se para constituir um paradigma linguístico denominado de cognitivo-funcional, cuja pauta de investigação se empenha em estudar a língua em uso, ainda buscamos demonstrar aproximações entre os paradigmas que compõem a perspectiva cognitivo-funcional. Em seguida, tratamos de expor uma concepção de gramática centrada no uso que é entendida como um conjunto de regularidades que são convencionalizadas pelo uso concreto nas diferentes situações discursivas. As questões de análise envolvem o discurso e a interpretação das estruturas linguísticas, considerando o seu funcionamento, nas quais, analisamos indícios de eventos icônicos em textos do gênero tira em quadrinhos, corroborando indicativos relativos às questões elencadas pelo viés cognitivo-funcional. Como apontamentos finais destacamos dois itens provenientes das análises que demonstram motivações icônicas, quais sejam: a quantidade informações implica na codificação morfossintática e a organização sintática tem relação motivada pela ordem temporal dos fatos e pelas experiências do locutor.

Evolutionary Pathways in BRCA1-Associated Breast Tumors

BRCA1-associated breast tumors display loss of BRCA1 and frequent somatic mutations of PTEN and TP53. Here we describe the analysis of BRCA1, PTEN, and p53 at the single cell level in 55 BRCA1-associated breast tumors and computational methods to predict the relative temporal order of somatic events, on the basis of the frequency of cells with single or combined alterations. Although there is no obligatory order of events, we found that loss of PTEN is the most common first event and is associated with basal-like subtype, whereas in the majority of luminal tumors, mutation of TP53 occurs first and mutant PIK3CA is rarely detected. We also observed intratumor heterogeneity for the loss of wild-type BRCA1 and increased cell proliferation and centrosome amplification in the normal breast epithelium of BRCA1 mutation carriers. Our results have important implications for the design of chemopreventive and therapeutic interventions in this high-risk patient population.

A negative semantic similarity effect on short-term order memory: Evidence from recency judgements

Speeded recency judgements were used to examine whether judgements concerning the relative temporal order in which two items were presented on a short eight-item, study list would be facilitated or hindered when the two items were from the same semantic category (related, R, items), relative to when they were from different categories (unrelated, U, items). Semantic similarity led to slower and less accurate recency judgements. To evaluate the extent that item memory contributes to recency judgement performance, I used speeded pair recognition and speeded two-alternative forced-choice (2AFC) recognition trials, in which the stimuli and designs were the same as in the recency judgement test. The type of test trial was manipulated between subjects (recency judgement vs pair recognition) or within participants (recency judgement and 2AFC recognition). Regardless of the between- or within-participants manipulation of recognition vs order memory tests, the pattern of recognition performance was very different from the pattern of recency judgement performance, indicating that semantic similarity had a negative effect on order memory per se. The explanation of the current findings offered by position-based order memory theories is discussed.

Differential temporo-parietal cortical networks that support relational and item-based recency judgments

There is a growing interest in the parietal cortical role for episodic memory retrieval. Previous functional magnetic resonance imaging (fMRI) studies of recency judgments, judgments of the relative temporal order of two studied items, have highlighted the involvement of the lateral prefrontal and medial temporal regions. However, the parietal cortical contribution to recency judgments has rarely been highlighted. To examine the parietal involvement, in this study, we conducted a re-analysis to increase the statistical power using three data sets (N=73) from our previous fMRI studies of recency judgments. Recency judgments can be achieved by at least two mechanisms, relational and item-based ones. It has been revealed that the left hippocampus/parahippocampal region is related to relational recency judgments, and that the right anterior temporal region is related to item-based recency judgments. We examined whether the parietal cortex is involved in these two types of recency judgments. Significant brain activity related to relational recency judgments was observed in the left ventral parietal region and, as reported previously, the left parahippocampal region. On the other hand, significant brain activity related to item-based recency judgments was observed in the left dorsal parietal region and, as reported previously, the right anterior temporal region. Furthermore, correlation analyses of resting-state BOLD signals detected significant correlations between the ventral parietal region and the parahippocampal region, as well as between the dorsal parietal region and anterior temporal region. These results suggest that the two temporo-parietal networks differentially contribute to relational and item-based recency judgments.

‘When Birds of a Feather Flock Together’: Synesthetic Correspondences Modulate Audiovisual Integration in Non-Synesthetes

BackgroundSynesthesia is a condition in which the stimulation of one sense elicits an additional experience, often in a different (i.e., unstimulated) sense. Although only a small proportion of the population is synesthetic, there is growing evidence to suggest that neurocognitively-normal individuals also experience some form of synesthetic association between the stimuli presented to different sensory modalities (i.e., between auditory pitch and visual size, where lower frequency tones are associated with large objects and higher frequency tones with small objects). While previous research has highlighted crossmodal interactions between synesthetically corresponding dimensions, the possible role of synesthetic associations in multisensory integration has not been considered previously.MethodologyHere we investigate the effects of synesthetic associations by presenting pairs of asynchronous or spatially discrepant visual and auditory stimuli that were either synesthetically matched or mismatched. In a series of three psychophysical experiments, participants reported the relative temporal order of presentation or the relative spatial locations of the two stimuli.Principal FindingsThe reliability of non-synesthetic participants' estimates of both audiovisual temporal asynchrony and spatial discrepancy were lower for pairs of synesthetically matched as compared to synesthetically mismatched audiovisual stimuli.ConclusionsRecent studies of multisensory integration have shown that the reduced reliability of perceptual estimates regarding intersensory conflicts constitutes the marker of a stronger coupling between the unisensory signals. Our results therefore indicate a stronger coupling of synesthetically matched vs. mismatched stimuli and provide the first psychophysical evidence that synesthetic congruency can promote multisensory integration. Synesthetic crossmodal correspondences therefore appear to play a crucial (if unacknowledged) role in the multisensory integration of auditory and visual information.

A critical component that activates the left inferior prefrontal cortex during interference resolution

Previous studies of proactive interference (PI) have revealed the involvement of the left inferior frontal gyrus (IFG) in resolution of PI during working memory/item recognition. PI resolution is thought to require: (1) inhibition of inappropriate attribution of familiarity to the probe and resultant inappropriate response tendencies; and (2) inhibition of PI per se regardless of the appropriateness of the attribution of familiarity. It is not clear, however, whether the IFG supports inhibition of inappropriate response tendencies or inhibition of PI per se. In the present functional magnetic resonance imaging study, we dissociate these possibilities using a recency judgment paradigm. Recency judgments, judgments of the relative temporal order of two studied items, provided an opportunity of examining three types of trials that differed in the way PI influenced the current trials: the trials where PI from previous trials was congruent with the current trials (C-PI trials); the trials where PI was incongruent with the current trials (I-PI trials); and the trials where no PI influenced the current trials (N-PI trials). Relative to the N-PI trials, the I-PI trials elicited the significant left IFG activation associated with PI resolution, consistent with previous studies using working memory/item recognition. We found that the IFG activation was related not to inhibition of inappropriate response tendencies (I-PI vs. C-PI), but to inhibition of PI per se (C-PI vs. N-PI). These results indicate that the left IFG plays its control role regardless of whether or not PI is congruent with correct performance of current trials.

Telling time from fossils: a phylogeny‐based approach to chronological ordering of paleobiotas

AbstractThe potential for using fossils for temporal ordering of sedimentary rocks is as old as historical geology itself. In spite of this, however, most current biostratigraphic and biochronologic techniques do not make use of phylogenetic information, but rely instead on some measure of species' presence or absence or their turnover in the fossil record. A common phylogenetic approach to biochronology has been to use “stage of evolution” arguments, whereas more rigorous, cladogram‐based methods have been proposed but have seen little use. Cladistic biochronologic analysis (CBA) is developed here as a new method for determining biochronologic order between paleobiotas based on the phylogenetic relationships of their constituent taxa. CBA is adapted from Brooks' parsimony analysis, and analyzes syntaxon information from clades that transcend a number of paleobiotas to determine relative temporal order among these paleobiotas. Because CBA is based on phylogenetic information, it is suited to problems where a good fossil record is available, but where stratigraphic or chronologic relationships are poorly constrained, such as the terrestrial vertebrate record. A practical example, based on the Cenozoic fossil record of North America, pits CBA against a test case in which the correct temporal order of biotas is known beforehand. The method successfully recovers correct temporal order between paleobiotas with reasonable levels of support, and is also shown to outperform a previously proposed cladistic biochronologic method. In a second example, CBA is used to achieve the first empirical temporal ordination for several Late Cretaceous localities in the Gobi Desert that produce fossils crucial to the understanding of modern amniote clades, but which have poorly resolved temporal relationships. CBA is sensitive to large amounts of extinction and poor sampling of the fossil record, but problems such as gaps in the fossil record (Lazarus taxa) can be dealt with efficiently through a number of a priori and a posteriori scoring techniques. CBA offers a novel approach for biochronologic analysis that is independent of, but complementary to and readily combinable with other chronologic/stratigraphic methods.© The Willi Hennig Society 2007.

PANDORA : THE TIME OF PRIORITY-AND GATES

Classical Fault Tree Analysis (FTA) can determine the effects of combinations of failure events on a system but cannot capture the significance of the temporal ordering of events, which may be critical. In this paper, we propose a temporal extension based on formal definition and use of Priority AND gates to allow relative temporal ordering and analysis of temporal relationships in FTA. In this work, the classical notion of minimal cut-sets is replaced with the notion of minimal cut-sequences and a methodology is proposed for qualitative analysis of temporal fault trees and the derivation of minimal cut-sequences. The approach is demonstrated on a generic two stage standby recovery system. The paper tentatively concludes that this type of temporal FTA can provide a more precise and ultimately more correct insight into the failure behaviour of a system.

Developmental constraints vs. variational properties: how pattern formation can help to understand evolution and development

This article suggests that apparent disagreements between the concept of developmental constraints and neo-Darwinian views on morphological evolution can disappear by using a different conceptualization of the interplay between development and selection. A theoretical framework based on current evolutionary and developmental biology and the concepts of variational properties, developmental patterns and developmental mechanisms is presented. In contrast with existing paradigms, the approach in this article is specifically developed to compare developmental mechanisms by the morphological variation they produce and the way in which their functioning can change due to genetic variation. A developmental mechanism is a gene network, which is able to produce patterns in space though the regulation of some cell behaviour (like signalling, mitosis, apoptosis, adhesion, etc.). The variational properties of a developmental mechanism are all the pattern transformations produced under different initial and environmental conditions or IS-mutations. IS-mutations are DNA changes that affect how two genes in a network interact, while T-mutations are mutations that affect the topology of the network itself. This article explains how this new framework allows predictions not only about how pattern formation affects variation, and thus phenotypic evolution, but also about how development evolves by replacement between pattern formation mechanisms. This article presents testable inferences about the evolution of the structure of development and the phenotype under different selective pressures. That is what kind of pattern formation mechanisms, in which relative temporal order, and which kind of phenotypic changes, are expected to be found in development.

Manifestation of function-follow-form in cultured neuronal networks

We expose hidden function-follow-form schemata in the recorded activity of cultured neuronal networks by comparing the activity with simulation results of a new modeling approach. Cultured networks grown from an arbitrary mixture of neuron and glia cells in the absence of external stimulations and chemical cues spontaneously form networks of different sizes (from 50 to several millions of neurons) that exhibit non-arbitrary complex spatio-temporal patterns of activity. The latter is marked by formation of a sequence of synchronized bursting events (SBEs)—short time windows (≈200 ms) of rapid neuron firing, separated by longer time intervals (seconds) of sporadic neuron firing. The new dynamical synapse and soma (DSS) model, used here, has been successful in generating sequences of SBEs with the same statistical scaling properties (over six time decades) as those of the small networks. Large networks generate statistically distinct sub-groups of SBEs, each with its own characteristic pattern of neuronal firing (‘fingerprint’). This special function (activity) motif has been proposed to emanate from a structural (form) motif—self-organization of the large networks into a fabric of overlapping sub-networks of about 1 mm in size. Here we test this function-follow-form idea by investigating the influence of the connectivity architecture of a model network (form) on the structure of its spontaneous activity (function). We show that a repertoire of possible activity states similar to the observed ones can be generated by networks with proper underlying architecture. For example, networks composed of two overlapping sub-networks exhibit distinct types of SBEs, each with its own characteristic pattern of neuron activity that starts at a specific sub-network. We further show that it is possible to regulate the temporal appearance of the different sub-groups of SBEs by an additional non-synaptic current fed into the soma of the modeled neurons. The ability to regulate the relative temporal ordering of different SBEs might endow the networks with higher plasticity and complexity. These findings call for additional mechanisms yet to be discovered. Recent experimental observations indicate that glia cells coupled to neuronal soma might generate such non-synaptic regulating currents.

Linear temporal sequences and their interpretation using midpoint relationships

The temporal interval relationships formalized by Allen, and later extended to accommodate semiintervals by Freksa, have been widely utilized in both data modeling and artificial intelligence research to facilitate reasoning between the relative temporal ordering of events. In practice, however, some modifications to the relationships are necessary when linear temporal sequences are provided, when event times are aggregated, or when data is supplied to a granularity which is larger than required. This paper discusses these modifications and outlines a solution to this problem which accommodates any available knowledge of interval midpoints.