Reverse-engineering the cortical architecture for controlled semantic cognition.

We employ a reverse-engineering approach to illuminate the neurocomputational building blocks that combine to support controlled semantic cognition: the storage and context-appropriate use of conceptual knowledge. By systematically varying the structure of a computational model and assessing the functional consequences, we identified the architectural properties that best promote some core functions of the semantic system. Semantic cognition presents a challenging test case, as the brain must achieve two seemingly contradictory functions: abstracting context-invariant conceptual representations across time and modalities, while producing specific context-sensitive behaviours appropriate for the immediate task. These functions were best achieved in models possessing a single, deep multimodal hub with sparse connections from modality-specific regions, and control systems acting on peripheral rather than deep network layers. The reverse-engineered model provides a unifying account of core findings in the cognitive neuroscience of controlled semantic cognition, including evidence from anatomy, neuropsychology and functional brain imaging

Zero-bias anomalies of point contact resistance due to adiabatic electron renormalization of dynamical defects

We study effect of the adiabatic electron renormalization on the parameters of the dynamical defects in the ballistic metallic point contact. The upper energy states of the ``dressed'' defect are shown to give a smaller contribution to a resistance of the contact than the lower energy ones. This holds both for the "classical" renormalization related to defect coupling with average local electron density and for the "mesoscopic" renormalization caused by the mesoscopic fluctuations of electronic density the dynamical defects are coupled with. In the case of mesoscopic renormalization one may treat the dynamical defect as coupled with Friedel oscillations originated by the other defects, both static and mobile. Such coupling lifts the energy degeneracy of the states of the dynamical defects giving different mesoscopic contribution to resistance, and provides a new model for the fluctuator as for the object originated by the electronic mesoscopic disorder rather than by the structural one. The correlation between the defect energy and the defect contribution to the resistance leads to zero-temperature and zero-bias anomalies of the point contact resistance. A comparison of these anomalies with those predicted by the Two Channel Kondo Model (TCKM) is made. It is shown, that although the proposed model is based on a completely different from TCKM physical background, it leads to a zero-bias anomalies of the point contact resistance, which are qualitatively similar to TCKM predictions.Comment: 6 pages, to be published in Phys. Rev.

Subcompartmentalisation of Proteins in the Rhoptries Correlates with Ordered Events of Erythrocyte Invasion by the Blood Stage Malaria Parasite

Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion. © 2012 Zuccala et al

Super-Resolution Dissection of Coordinated Events during Malaria Parasite Invasion of the Human Erythrocyte

Erythrocyte invasion by the merozoite is an obligatory stage in Plasmodium parasite infection and essential to malaria disease progression. Attempts to study this process have been hindered by the poor invasion synchrony of merozoites from the only in vitro culture-adapted human malaria parasite, Plasmodium falciparum. Using fluorescence, three-dimensional structured illumination, and immunoelectron microscopy of filtered merozoites, we analyze cellular and molecular events underlying each discrete step of invasion. Monitoring the dynamics of these events revealed that commitment to the process is mediated through merozoite attachment to the erythrocyte, triggering all subsequent invasion events, which then proceed without obvious checkpoints. Instead, coordination of the invasion process involves formation of the merozoite-erythrocyte tight junction, which acts as a nexus for rhoptry secretion, surface-protein shedding, and actomyosin motor activation. The ability to break down each molecular step allows us to propose a comprehensive model for the molecular basis of parasite invasion. © 2011 Elsevier Inc

Strategies for Improved CALIPSO Aerosol Optical Depth Estimates

In the spring of 2010, the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) project will be releasing version 3 of its level 2 data products. In this paper we describe several changes to the algorithms and code that yield substantial improvements in CALIPSO's retrieval of aerosol optical depths (AOD). Among these are a retooled cloud-clearing procedure and a new approach to determining the base altitudes of aerosol layers in the planetary boundary layer (PBL). The results derived from these modifications are illustrated using case studies prepared using a late beta version of the level 2 version 3 processing code

Flicker Noise Induced by Dynamic Impurities in a Quantum Point Contact

We calculate low-frequency noise (LFN) in a quantum point contact (QPC) which is electrostatically defined in a 2D electron gas of a GaAs-AlGaAs heterostructure. The conventional source of LFN in such systems are scattering potentials fluctuating in time acting upon injected electrons. One can discriminate between potentials of different origin -- noise may be caused by the externally applied gate- and source-drain voltages, the motion of defects with internal degrees of freedom close to the channel, electrons hopping between localized states in the doped region, etc. In the present study we propose a model of LFN based upon the assumption that there are many dynamic defects in the surrounding of a QPC. A general expression for the time-dependent current-current correlation function is derived and applied to a QPC with quantized conductance. It is shown that the level of LFN is significantly different at and between the steps in a plot of the conductance vs. gate voltage. On the plateaus, the level of noise is found to be low and strongly model-dependent. At the steps, LFN is much larger and only weakly model-dependent. As long as the system is biased to be at a fixed position relative the conductance step,Comment: 26 revtex APR 94-4

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions

Converse Smith-Martin cell cycle kinetics by transformed B lymphocytes

Recent studies using direct live cell imaging have reported that individual B lymphocytes have correlated transit times between their G1 and S/G2/M phases. This finding is in contradiction with the influential model of Smith and Martin that assumed the bulk of the total cell cycle time variation arises in the G1 phase of the cell cycle with little contributed by the S/G2/M phase. Here we extend these studies to examine the relation between cell cycle phase lengths in two B lymphoma cell lines. We report that transformed B lymphoma cells undergo a short G1 period that displays little correlation with the time taken for the subsequent S/G2/M phase. Consequently, the bulk of the variation noted for total division times within a population is found in the S/G2/M phases and not the G1 phase. Models that reverse the expected source of variation and assume a single deterministic time in G1 followed by a lag + exponential distribution for S/G2/M fit the data well. These models can be improved further by adopting two sequential distributions or by using the stretched lognormal model developed for primary lymphocytes. We propose that shortening of G1 transit times and uncoupling from other cell cycle phases may be a hallmark of lymphocyte transformation that could serve as an observable phenotypic marker of cancer evolution.K. Pham, A. Kan, L. Whitehead, R. J. Hennessy, K. Rogers, P. D. Hodgki