Complexity of CEBPA dysregulation in human acute myeloid leukemia

The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is crucial for normal development of granulocytes. Various mechanisms have been identified how CEBPA function is dysregulated in patients with acute myeloid leukemia (AML). In particular, dominant-negative mutations located either at the N- or the C terminus of the CEBPA gene are observed in roughly 10% of AML patients, either in the combination on separate alleles or as sole mutation. Clinically significant complexity exists among AML with CEBPA mutations, and patients with double CEBPA mutations seem to have a more favorable course of the disease than patients with a single mutation. In addition, myeloid precursor cells of healthy carriers with a single germ-line CEBPA mutation evolve to overt AML by acquiring a second sporadic CEBPA mutation. This review summarizes recent reports on dysregulation of CEBPA function at various levels in human AML and therapeutic concepts targeting correction of CEBPA activity. The currently available data are persuasive evidence that impaired CEBPA function contributes directly to the development of AML, whereas restoring CEBPA function represents a promising target for novel therapeutic strategies in AML.

Augmenting Static Source Views in IDEs with Dynamic Metrics

Mainstream IDEs such as Eclipse support developers in managing software projects mainly by offering static views of the source code. Such a static perspective neglects any information about runtime behavior. However, object-oriented programs heavily rely on polymorphism and late-binding, which makes them difficult to understand just based on their static structure. Developers thus resort to debuggers or profilers to study the system's dynamics. However, the information provided by these tools is volatile and hence cannot be exploited to ease the navigation of the source space. In this paper we present an approach to augment the static source perspective with dynamic metrics such as precise runtime type information, or memory and object allocation statistics. Dynamic metrics can leverage the understanding for the behavior and structure of a system. We rely on dynamic data gathering based on aspects to analyze running Java systems. By solving concrete use cases we illustrate how dynamic metrics directly available in the IDE are useful. We also comprehensively report on the efficiency of our approach to gather dynamic metrics.

Senseo: Enriching Eclipse's Static Source Views with Dynamic Metrics

Maintaining object-oriented systems that use inheritance and polymorphism is difficult, since runtime information, such as which methods are actually invoked at a call site, is not visible in the static source code. We have implemented Senseo, an Eclipse plugin enhancing Eclipse's static source views with various dynamic metrics, such as runtime types, the number of objects created, or the amount of memory allocated in particular methods.

Transfer of spatial knowledge from a virtual environment to reality: Impact of route complexity and subject’s strategy on the exploration mode

The use of virtual reality as tool in the area of spatial cognition raises the question of the quality of learning transfer from a virtual to a real environment. It is first necessary to determine with healthy subjects, the cognitive aids that improve the quality of transfer and the conditions required, especially since virtual reality can be used as effective tool in cognitive rehabilitation. The purpose of this study was to investigate the influence of the exploration mode of virtual environment (Passive vs. Active) according to Route complexity (Simple vs. Complex) on the quality of spatial knowledge transfer in three spatial tasks. Ninety subjects (45 men and 45 women) participated. Spatial learning was evaluated by Wayfinding, sketch-mapping and picture classification tasks in the context of the Bordeaux district. In the Wayfinding task, results indicated that active learning in a Virtual Environment (VE) increased the performances compared to the passive learning condition, irrespective of the route complexity factor. In the Sketch-mapping task, active learning in a VE helped the subjects to transfer their spatial knowledge from the VE to reality, but only when the route was complex. In the Picture classification task, active learning in a VE when the route was complex did not help the subjects to transfer their spatial knowledge. These results are explained in terms of knowledge levels and frame/strategy of reference [SW75, PL81, TH82].

Path Dependence in Decision-Making Processes: Exploring the Impact of Complexity under Increasing Returns

The development of path-dependent processes basically refers to positive feedback in terms of increasing returns as the main driving forces of such processes. Furthermore, path dependence can be affected by context factors, such as different degrees of complexity. Up to now, it has been unclear whether and how different settings of complexity impact path-dependent processes and the probability of lock-in. In this paper we investigate the relationship between environmental complexity and path dependence by means of an experimental study. By focusing on the mode of information load and decision quality in chronological sequences, the study explores the impact of complexity on decision-making processes. The results contribute to both the development of path-dependence theory and a better understanding of decision-making behavior under conditions of positive feedback. Since previous path research has mostly applied qualitative case-study research and (to a minor part) simulations, this paper makes a further contribution by establishing an experimental approach for research on path dependence.

Single-dose piracetam effects on global complexity measures of human spontaneous multichannel EEG

Global complexity of 47-channel resting electroencephalogram (EEG) of healthy young volunteers was studied after intake of a single dose of a nootropic drug (piracetam, Nootropil® UCB Pharma) in 12 healthy volunteers. Four treatment levels were used: 2.4, 4.8, 9.6 g piracetam and placebo. Brain electric activity was assessed through Global Dimensional Complexity and Global Omega-Complexity as quantitative measures of the complexity of the trajectory of multichannel EEG in state space. After oral ingestion (1–1.5 h), both measures showed significant decreases from placebo to 2.4 g piracetam. In addition, Global Dimensional Complexity showed a significant return to placebo values at 9.6 g piracetam. The results indicate that a single dose of piracetam dose-dependently affects the spontaneous EEG in normal volunteers, showing effects at the lowest treatment level. The decreased EEG complexity is interpreted as increased cooperativity of brain functional processes.

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.