Temporal and Urban Peripheries in Systems Thinking

The “Temporal and Urban Peripheries” is the fall project of the final year of the Architecture program of Izmir University of Economics in Turkey. With a critical and contextual look at the built environment, the studio focuses on the significance of the incorporation of history, urban design, and parametrics in architectural design. This short article presents the thrust of the studio, basic concepts, the process, and outcomes.

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodelling genes

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.

A spatio-temporal 2D-models framework for human pose recovery in monocular sequences

This paper addresses the pose recovery problem of a particular articulated object: the human body. In this model-based approach, the 2D-shape is associated to the corresponding stick figure allowing the joint segmentation and pose recovery of the subject observed in the scene. The main disadvantage of 2D-models is their restriction to the viewpoint. To cope with this limitation, local spatio-temporal 2D-models corresponding to many views of the same sequences are trained, concatenated and sorted in a global framework. Temporal and spatial constraints are then considered to build the probabilistic transition matrix (PTM) that gives a frame to frame estimation of the most probable local models to use during the fitting procedure, thus limiting the feature space. This approach takes advantage of 3D information avoiding the use of a complex 3D human model. The experiments carried out on both indoor and outdoor sequences have demonstrated the ability of this approach to adequately segment pedestrians and estimate their poses independently of the direction of motion during the sequence. (c) 2008 Elsevier Ltd. All rights reserved.

Exploiting spatio-temporal constraints for robust 2D pose tracking

We present a Spatio-temporal 2D Models Framework (STMF) for 2D-Pose tracking. Space and time are discretized and a mixture of probabilistic "local models" is learnt associating 2D Shapes and 2D Stick Figures. Those spatio-temporal models generalize well for a particular viewpoint and state of the tracked action but some spatio-temporal discontinuities can appear along a sequence, as a direct consequence of the discretization. To overcome the problem, we propose to apply a Rao-Blackwellized Particle Filter (RBPF) in the 2D-Pose eigenspace, thus interpolating unseen data between view-based clusters. The fitness to the images of the predicted 2D-Poses is evaluated combining our STMF with spatio-temporal constraints. A robust, fast and smooth human motion tracker is obtained by tracking only the few most important dimensions of the state space and by refining deterministically with our STMF.

Temporal extension of Laplacian Eigenmaps for unsupervised dimensionality reduction of time series

A novel non-linear dimensionality reduction method, called Temporal Laplacian Eigenmaps, is introduced to process efficiently time series data. In this embedded-based approach, temporal information is intrinsic to the objective function, which produces description of low dimensional spaces with time coherence between data points. Since the proposed scheme also includes bidirectional mapping between data and embedded spaces and automatic tuning of key parameters, it offers the same benefits as mapping-based approaches. Experiments on a couple of computer vision applications demonstrate the superiority of the new approach to other dimensionality reduction method in term of accuracy. Moreover, its lower computational cost and generalisation abilities suggest it is scalable to larger datasets. © 2010 IEEE.

Events: Temporal and Eternal (in preparation)

This monograph develops a theory of events which provides the foundation for a plausible and coherent account of God’s relation to time, and which has independent appeal (independent, that is, of theological considerations). The book is divided into three parts. The first part involves an investigation of those fundamental aspects of time which have important implications for the nature of events, such as whether time is substantival or relational, and whether time is continuous, dense, or discrete. This part also includes a chapter on how these issues relate to different interpretations of the special theory of relativity. The second part involves a defense of the fundamentality of events, and the development of a theory of events in time. The third part considers ways in which we might plausibly conceive of events as eternal entities. This involves an investigation of different ways of characterizing divine eternity, and then an analysis of the possible relations these ways bear to the antecedently developed theory of temporal events. The thought here is that there are certain characteristics of temporal events which can be assimilated to eternity, and that by evaluating the extent to which different theories of divine eternity allow for this assimilation, we will be able to determine which of those theories is most plausible, and therefore which conception of God’s relation to time is most plausible. The basis of this evaluation will be the theory’s ability to coherently account for God’s knowledge of, and interaction with, the created temporal world. One specific issue here is how to account for God’s knowledge of the future free actions of humans (an issue that I address in 'Eternity, Knowledge, and Freedom'), but there are many other difficulties associated with God’s relation to time, such as God’s creation of contingent time, God’s knowledge of what is happening now, God’s dialogue with humans, and God’s causally interacting with the temporal world in general. A successful theory of eternal events, and, in particular, divine events, will provide a framework for dealing with these difficulties.

I have not yet sough a publisher for this work, but intend to do so in 2013, with a target publication date of 2014.

Assessing the extent to which temporal changes in waterbird community composition are driven by either local, regional or global factors.

1. Lough Neagh and Lough Beg Special Protection Area (SPA, hereafter Lough Neagh) is an important non-estuarine site in Britain and Ireland for overwintering wildfowl. Multivariate analysis of the winter counts showed a state-shift in the waterbird community following winter 2000/2001, mostly due to rapid declines in abundance (46–57% declines in the mean mid-winter January counts between 1993–2000 and 2002–2009) of members of the diving duck guild (pochard Aythya ferina, tufted duck Aythya fuligula and goldeneye Bucephala clangula) and coot (Fulica atra), a submerged macrophyte feeder.
2. Only pochard showed correlations between declines at Lough Neagh and those of overall species flyway population indices to suggest that global changes could contribute to declines at the site. However, indices from the Republic of Ireland showed no overall decline in the rest of Ireland. Tufted duck indices at the site were inversely related to indices in Great Britain. Lough Neagh goldeneye indices were positively correlated with indices in the Republic of Ireland and Great Britain, suggesting that short-stopping could contribute to declines at the site. Coot declines at Lough Neagh did not correlate with trends elsewhere, suggesting local factors involved in the decline.
3. These analyses indicate that although there are potentially different explanations for the dramatic declines in these four waterbird species at this site, the simultaneous nature of the declines across two feeding guilds strongly
suggest that local factors (such as loss of submerged macrophytes and benthic invertebrates) were involved. An assessment of the food supply, local disturbance and other factors at Lough Neagh is required to find an explanation for the observed adverse trends in wintering numbers of the affected species.
4. This study highlights the potential of waterbird community structure to reflect the status of aquatic systems, but confirms the need to establish site-specific factors responsible for the observed changes in abundance of key waterbird species at a site.

A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers

BRCA1 encodes a tumour suppressor protein that plays pivotal roles in homologous recombination (HR) DNA repair, cell-cycle checkpoints, and transcriptional regulation. BRCA1 germline mutations confer a high risk of early-onset breast and ovarian cancer. In more than 80% of cases, tumours arising in BRCA1 germline mutation carriers are oestrogen receptor (ER)-negative; however, up to 15% are ER-positive. It has been suggested that BRCA1 ER-positive breast cancers constitute sporadic cancers arising in the context of a BRCA1 germline mutation rather than being causally related to BRCA1 loss-of-function. Whole-genome massively parallel sequencing of ER-positive and ER-negative BRCA1 breast cancers, and their respective germline DNAs, was used to characterize the genetic landscape of BRCA1 cancers at base-pair resolution. Only BRCA1 germline mutations, somatic loss of the wild-type allele, and TP53 somatic mutations were recurrently found in the index cases. BRCA1 breast cancers displayed a mutational signature consistent with that caused by lack of HR DNA repair in both ER-positive and ER-negative cases. Sequencing analysis of independent cohorts of hereditary BRCA1 and sporadic non-BRCA1 breast cancers for the presence of recurrent pathogenic mutations and/or homozygous deletions found in the index cases revealed that DAPK3, TMEM135, KIAA1797, PDE4D, and GATA4 are potential additional drivers of breast cancers. This study demonstrates that BRCA1 pathogenic germline mutations coupled with somatic loss of the wild-type allele are not sufficient for hereditary breast cancers to display an ER-negative phenotype, and has led to the identification of three potential novel breast cancer genes (ie DAPK3, TMEM135, and GATA4).

Using temporal analysis of products and flux response technology to determine diffusion coefficients in catalytic monoliths

The importance of accurately measuring gas diffusivity in porous materials has led to a number of methods being developed. In this study the Temporal Analysis of Products (TAP) reactor and Flux Response Technology (FRT) have been used to examine the diffusivity in the washcoat supported on cordierite monoliths. Herein, the molecular diffusion of propane within four monoliths with differently prepared alumina/CeZrOx washcoats was investigated as a function of temperature. Moment-based analysis of the observed TAP responses led to the calculation of the apparent intermediate gas constant, Kp, that characterises adsorption into the mesoporous network and apparent time delay, tapp, that characterises residence time in the mesoporous network. Additionally, FRT has been successfully adapted as an extensive in situ perturbation technique in measuring intraphase diffusion coefficients in the washcoats of the same four monolith samples. The diffusion coefficients obtained by moment-based analysis of TAP responses are larger than the coefficients determined by zero length column (ZLC) analysis of flux response profiles with measured values of the same monolith samples between 20 and 100 °C ranging from 2–5×10^-9 m² s^-1 to 4–8×10^-10 m² s^-1, respectively. The TAP and FRT data, therefore, provide a range of the lower and upper limits of diffusivity, respectively. The reported activation energies and diffusivities clearly correlate with the difference in the washcoat structure of different monolith samples.

How position, velocity, and temporal information combine in the prospective control of catching:data and model

The cerebral cortex contains circuitry for continuously computing properties of the environment and one's body, as well as relations among those properties. The success of complex perceptuomotor performances requires integrated, simultaneous use of such relational information. Ball catching is a good example as it involves reaching and grasping of visually pursued objects that move relative to the catcher. Although integrated neural control of catching has received sparse attention in the neuroscience literature, behavioral observations have led to the identification of control principles that may be embodied in the involved neural circuits. Here, we report a catching experiment that refines those principles via a novel manipulation. Visual field motion was used to perturb velocity information about balls traveling on various trajectories relative to a seated catcher, with various initial hand positions. The experiment produced evidence for a continuous, prospective catching strategy, in which hand movements are planned based on gaze-centered ball velocity and ball position information. Such a strategy was implemented in a new neural model, which suggests how position, velocity, and temporal information streams combine to shape catching movements. The model accurately reproduces the main and interaction effects found in the behavioral experiment and provides an interpretation of recently observed target motion-related activity in the motor cortex during interceptive reaching by monkeys. It functionally interprets a broad range of neurobiological and behavioral data, and thus contributes to a unified theory of the neural control of reaching to stationary and moving targets.

Long-range Transcriptome Sequencing Reveals Cancer Cell Growth Regulatory Chimeric mRNA

mRNA chimeras from chromosomal translocations often play a role as transforming oncogenes. However, cancer transcriptomes also contain mRNA chimeras that may play a role in tumor development, which arise as transcriptional or post-transcriptional events. To identify such chimeras, we developed a deterministic screening strategy for long-range sequence analysis. High-throughput, long-read sequencing was then performed on cDNA libraries from major tumor histotypes and corresponding normal tissues. These analyses led to the identification of 378 chimeras, with an unexpectedly high frequency of expression (˜2 x 10(-5) of all mRNA). Functional assays in breast and ovarian cancer cell lines showed that a large fraction of mRNA chimeras regulates cell replication. Strikingly, chimeras were shown to include both positive and negative regulators of cell growth, which functioned as such in a cell-type-specific manner. Replication-controlling chimeras were found to be expressed by most cancers from breast, ovary, colon, uterus, kidney, lung, and stomach, suggesting a widespread role in tumor development.

Structural brain abnormalities in male schizophrenics reflect fronto-temporal dissociation

Background. Many studies have separately reported abnormalities of frontal and temporal lobe structures in schizophrenia, but little is known of structural fronto-temporal associations in this condition. We investigated whether male patients with chronic schizophrenia would show abnormal patterns of correlation between regional brain volumes.

Methods. Structural magnetic resonance images of the brain in 42 patients were compared with 43 matched unaffected controls. We explored the pattern of association between regional brain volumes by correlational analyses, and non-parametrically tested for significance of between-group differences by randomization.

Results. The schizophrenics demonstrated significant volume deficits in several brain regions (left temporal lobe and hippocampus, right dorsolateral prefrontal cortex), and significant volume increases in the ventricular system (third ventricle and left temporal horn of the lateral ventricle). Controls demonstrated large positive correlations (r > 0.4) between prefrontal and temporal lobe regions. By contrast, inter-regional correlations significantly reduced in schizophrenics included those between prefrontal, anterior cingulate and temporal regions, and between posterior cingulate and hippocampus (P < 0.05). The most salient abnormality in patients was a dissociation between prefrontal and superior temporal gyrus volumes (P < 0.01).

Conclusions. These results support the existence of a relative 'fronto-temporal dissociation' in schizophrenia which we suggest may be due to lack of mutually trophic influences during frontal and temporal lobe development.

Problem-solving and spatial working memory in patients with schizophrenia and with focal frontal and temporal lobe lesions

Problem-solving ability was investigated in 25 DSM-IIIR schizophrenic (SC) patients using the Tower of Hanoi (TOH) task. Their performance was compared to that of: (1) 22 patients with neurosurgical unilateral prefrontal lesions, 11 left (LF) and 10 right hemisphere (RF); (2) 38 patients with unilateral temporal lobectomies, 19 left (LT) and 19 right (RT); and (3) 44 matched control subjects. Like the RT and LF group, the schizophrenics were significantly impaired on the TOH. The deficit shown by the schizophrenic group was equivalent whether or not the problems to be solved included goal-subgoal conflicts, unlike the LF group who were impaired specifically on these problems. The nature of the SC deficit was also distinct from that of the RT group, in that the problem-solving deficit remained after controlling for the effects of spatial memory performance. This study indicates, therefore, that neither focal frontal nor temporal lobe damage sustained in adult life is a sufficient explanation for the problem-solving deficits found in patients with schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserved.