Postmortem studies in schizophrenia

For over a century, postmortem studies have played a central part in the search for the structural and biochemical pathology of schizophrenia. However, for most of this time, little progress has been made. Recently, the situation has begun to change, helped by the emergence of more powerful methodologies and research designs, and by the availability of brain imaging to provide complementary information. As a result, it can now be clearly concluded that there are structural cerebral abnormalities in schizophrenia that are intrinsic to the disorder. The neuropathological process is not primarily degenerative, but involves a change in the normal cytoarchitecture of the brain, probably originating in development. Neurochemically, there is postmortem evidence for alterations in several transmitter systems including dopamine, glutamate, serotonin, and γ-aminobutyric acid (GABA). The cardinal findings are reviewed here, together with a consideration of the conceptual and methodological issues that face postmortem studies of schizophrenia

Assessment of the environmental toxicity and carcinogenicity of tungsten-based shot.

The toxicity of elemental tungsten released from discharged shot was assessed against previous studies that established a 1% toxic threshold for soil organisms. Extremely heavy theoretical shot loadings of 69,000 shot/ha were used to generate estimated environmental concentrations (EEC) for two brands of tungsten-based shot containing 51% and 95% tungsten. The corresponding tungsten EEC values were 6.5–13.5 mg W/kg soil, far below the 1% toxic threshold. The same shot loading in water produced tungsten EEC values of 2.1–4.4 mg W/L, levels that are not toxic under experimental conditions. Pure tungsten has not been shown to exhibit carcinogenic properties when ingested or embedded in animal tissues, but nickel, with which it is often alloyed, has known carcinogenicity. Given the large number of waterfowl that carry shot embedded in their body, it is advisable to screen lead shot substitutes for their carcinogenic potential through intra-muscular implantation

Quantum transport in semiconductor quantum dot superlattices: electron-phonon resonances and polaron effects

Electron transport in periodic quantum dot arrays in the presence of interactions with phonons was investigated using the formalism of nonequilibrium Green's functions. The self-consistent Born approximation was used to model the self-energies. Its validity was checked by comparison with the results obtained by direct diagonalization of the Hamiltonian of interacting electrons and longitudinal optical phonons. The nature of charge transport at electron -- phonon resonances was investigated in detail and contributions from scattering and coherent tunnelling to the current were identified. It was found that at larger values of the structure period the main peak in the current -- field characteristics exhibits a doublet structure which was shown to be a transport signature of polaron effects. At smaller values of the period, electron -- phonon resonances cause multiple peaks in the characteristics. A phenomenological model for treatment of nonuniformities of a realistic quantum dot ensemble was also introduced to estimate the influence of nonuniformities on current -- field characteristics

Detecting early signs of depressive and manic episodes in patients with bipolar disorder using the signature-based model

Recurrent major mood episodes and subsyndromal mood instability cause substantial disability in patients with bipolar disorder. Early identification of mood episodes enabling timely mood stabilisation is an important clinical goal. Recent technological advances allow the prospective reporting of mood in real time enabling more accurate, efficient data capture. The complex nature of these data streams in combination with challenge of deriving meaning from missing data mean pose a significant analytic challenge. The signature method is derived from stochastic analysis and has the ability to capture important properties of complex ordered time series data. To explore whether the onset of episodes of mania and depression can be identified using self-reported mood data.Comment: 12 pages, 3 tables, 10 figure

Symmetry of k·p Hamiltonian in pyramidal InAs/GaAs quantum dots: Application to the calculation of electronic structure

A method for the calculation of the electronic structure of pyramidal self-assembled InAs/GaAs quantum dots is presented. The method is based on exploiting the C-4 symmetry of the 8-band k·p Hamiltonian with the strain taken into account via the continuum mechanical model. The operators representing symmetry group elements were represented in the plane wave basis and the group projectors were used to find the symmetry adapted basis in which the corresponding Hamiltonian matrix is block diagonal with four blocks of approximately equal size. The quantum number of total quasiangular momentum is introduced and the states are classified according to its value. Selection rules for interaction with electromagnetic field in the dipole approximation are derived. The method was applied to calculate electron and hole quasibound states in a periodic array of vertically stacked pyramidal self-assembled InAs/GaAs quantum dots for different values of the distance between the dots and external axial magnetic field. As the distance between the dots in an array is varied, an interesting effect of simultaneous change of ground hole state symmetry, type, and the sign of miniband effective mass is predicted. This effect is explained in terms of the change of biaxial strain. It is also found that the magnetic field splitting of Kramer's double degenerate states is most prominent for the first and second excited state in the conduction band and that the magnetic field can both separate otherwise overlapping minibands and concatenate otherwise nonoverlapping minibands

Visual Working Memory Is Independent of the Cortical Spacing Between Memoranda.

The sensory recruitment hypothesis states that visual short-term memory is maintained in the same visual cortical areas that initially encode a stimulus' features. Although it is well established that the distance between features in visual cortex determines their visibility, a limitation known as crowding, it is unknown whether short-term memory is similarly constrained by the cortical spacing of memory items. Here, we investigated whether the cortical spacing between sequentially presented memoranda affects the fidelity of memory in humans (of both sexes). In a first experiment, we varied cortical spacing by taking advantage of the log-scaling of visual cortex with eccentricity, presenting memoranda in peripheral vision sequentially along either the radial or tangential visual axis with respect to the fovea. In a second experiment, we presented memoranda sequentially either within or beyond the critical spacing of visual crowding, a distance within which visual features cannot be perceptually distinguished due to their nearby cortical representations. In both experiments and across multiple measures, we found strong evidence that the ability to maintain visual features in memory is unaffected by cortical spacing. These results indicate that the neural architecture underpinning working memory has properties inconsistent with the known behavior of sensory neurons in visual cortex. Instead, the dissociation between perceptual and memory representations supports a role of higher cortical areas such as posterior parietal or prefrontal regions or may involve an as yet unspecified mechanism in visual cortex in which stimulus features are bound to their temporal order.SIGNIFICANCE STATEMENT Although much is known about the resolution with which we can remember visual objects, the cortical representation of items held in short-term memory remains contentious. A popular hypothesis suggests that memory of visual features is maintained via the recruitment of the same neural architecture in sensory cortex that encodes stimuli. We investigated this claim by manipulating the spacing in visual cortex between sequentially presented memoranda such that some items shared cortical representations more than others while preventing perceptual interference between stimuli. We found clear evidence that short-term memory is independent of the intracortical spacing of memoranda, revealing a dissociation between perceptual and memory representations. Our data indicate that working memory relies on different neural mechanisms from sensory perception

On the philosophy of modeling—reply to a comment by M. R. DroopX

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110088/1/lno19782320385.pd

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery

Polarization transitions in interacting ring 1D arrays

Periodic nanostructures can display the dynamics of arrays of atoms while enabling the tuning of interactions in ways not normally possible in Nature. We examine one dimensional arrays of a ``synthetic atom,'' a one dimensional ring with a nearest neighbor Coulomb interaction. We consider the classical limit first, finding that the singly charged rings possess antiferroelectric order at low temperatures when the charge is discrete, but that they do not order when the charge is treated as a continuous classical fluid. In the quantum limit Monte Carlo simulation suggests that the system undergoes a quantum phase transition as the interaction strength is increased. This is supported by mapping the system to the 1D transverse field Ising model. Finally we examine the effect of magnetic fields. We find that a magnetic field can alter the electrostatic phase transition producing a ferroelectric groundstate, solely through its effect of shifting the eigenenergies of the quantum problem.Comment: 12 pages in two column format, 18 figure