Biaxial nematic phases in fluids of hard board-like particles

We use density-functional theory, of the fundamental-measure type, to study the relative stability of the biaxial nematic phase, with respect to non-uniform phases such as smectic and columnar, in fluids made of hard board-like particles with sizes $\sigma_1>\sigma_2>\sigma_3$. A restricted-orientation (Zwanzig) approximation is adopted. Varying the ratio $\kappa_1=\sigma_1/\sigma_2$ while keeping $\kappa_2=\sigma_2/\sigma_3$, we predict phase diagrams for various values of $\kappa_2$ which include all the uniform phases: isotropic, uniaxial rod- and plate-like nematics, and biaxial nematic. In addition, spinodal instabilities of the uniform phases with respect to fluctuations of the smectic, columnar and plastic-solid type, are obtained. In agreement with recent experiments, we find that the biaxial nematic phase begins to be stable for $\kappa_2\simeq 2.5$. Also, as predicted by previous theories and simulations on biaxial hard particles, we obtain a region of biaxility centred on $\kappa_1\approx\kappa_2$ which widens as $\kappa_2$ increases. For \kappa_2\agt 5 the region $\kappa_2\approx\kappa_1$ of the packing-fraction vs. $\kappa_1$ phase diagrams exhibits interesting topologies which change qualitatively with $\kappa_2$. We have found that an increasing biaxial shape anisotropy favours the formation of the biaxial nematic phase. Our study is the first to apply FMT theory to biaxial particles and, therefore, it goes beyond the second-order virial approximation. Our prediction that the phase diagram must be asymmetric is a genuine result of the present approach, which is not accounted for by previous studies based on second-order theories.Comment: Preprint format. 18 pages, 5 figure

Phase behaviour of binary mixtures of diamagnetic colloidal platelets in an external magnetic field

Using fundamental measure density functional theory we investigate paranematic-nematic and nematic-nematic phase coexistence in binary mixtures of circular platelets with vanishing thicknesses. An external magnetic field induces uniaxial alignment and acts on the platelets with a strength that is taken to scale with the platelet area. At particle diameter ratio lambda=1.5 the system displays paranematic-nematic coexistence. For lambda=2, demixing into two nematic states with different compositions also occurs, between an upper critical point and a paranematic-nematic-nematic triple point. Increasing the field strength leads to shrinking of the coexistence regions. At high enough field strength a closed loop of immiscibility is induced and phase coexistence vanishes at a double critical point above which the system is homogeneously nematic. For lambda=2.5, besides paranematic-nematic coexistence, there is nematic-nematic coexistence which persists and hence does not end in a critical point. The partial orientational order parameters along the binodals vary strongly with composition and connect smoothly for each species when closed loops of immiscibility are present in the corresponding phase diagram.Comment: 9 pages, to appear in J.Phys:Condensed Matte

Impaired Cerebellar Functional Connectivity in Schizophrenia Patients and Their Healthy Siblings

The long-standing notion of schizophrenia as a disorder of connectivity is supported by emerging evidence from recent neuroimaging studies, suggesting impairments of both structural and functional connectivity in schizophrenia. However, investigations are generally restricted to supratentorial brain regions, thereby excluding the cerebellum. As increasing evidence suggests that the cerebellum contributes to cognitive and affective processing, aberrant connectivity in schizophrenia may include cerebellar dysconnectivity. Moreover, as schizophrenia is highly heritable, unaffected family members of schizophrenia patients may exhibit similar connectivity profiles. The present study applies resting-state functional magnetic resonance imaging to determine cerebellar functional connectivity profiles, and the familial component of cerebellar connectivity profiles, in 62 schizophrenia patients and 67 siblings of schizophrenia patients. Compared to healthy control subjects, schizophrenia patients showed impaired functional connectivity between the cerebellum and several left-sided cerebral regions, including the hippocampus, thalamus, middle cingulate gyrus, triangular part of the inferior frontal gyrus, supplementary motor area, and lingual gyrus (all p < 0.0025, whole-brain significant). Importantly, siblings of schizophrenia patients showed several similarities to patients in cerebellar functional connectivity, suggesting that cerebellar dysconnectivity in schizophrenia might be related to familial factors. In conclusion, our findings suggest that dysconnectivity in schizophrenia involves the cerebellum and that this defect may be related to the risk to develop the illness

Motor Network Degeneration in Amyotrophic Lateral Sclerosis: A Structural and Functional Connectivity Study

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by motor neuron degeneration. How this disease affects the central motor network is largely unknown. Here, we combined for the first time structural and functional imaging measures on the motor network in patients with ALS and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Structural measures included whole brain cortical thickness and diffusion tensor imaging (DTI) of crucial motor tracts. These structural measures were combined with functional connectivity analysis of the motor network based on resting state fMRI. Focal cortical thinning was observed in the primary motor area in patients with ALS compared to controls and was found to correlate with disease progression. DTI revealed reduced FA values in the corpus callosum and in the rostral part of the corticospinal tract. Overall functional organisation of the motor network was unchanged in patients with ALS compared to healthy controls, however the level of functional connectedness was significantly correlated with disease progression rate. Patients with increased connectedness appear to have a more progressive disease course. CONCLUSIONS/SIGNIFICANCE: We demonstrate structural motor network deterioration in ALS with preserved functional connectivity measures. The positive correlation between functional connectedness of the motor network and disease progression rate could suggest spread of disease along functional connections of the motor network

DEVELOPMENT OF INACTIVATED POLIO VACCINE FROM ATTENUATED SABIN STRAINS FOR CLINICAL STUDIES AND TECHNOLOGY-TRANSFER PURPOSES

Recently, responding to WHO’s call for new polio vaccines, the development of Sabin-IPV (injectable, formalin-Inactivated Polio Vaccine, based on attenuated ‘Sabin’ polio virus strains) was initated at NVI. This activity plays an important role in the WHO polio eradication strategy. The use of Sabin instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel, process development, optimization and formulation research is being carried out to further modernize the process and reduce cost per dose. The lab-scale accelerated process development, product characterization, clinical lot production, and preparations for technology transfer will be discussed. Multivariate data analysis (MVDA) was applied on data from current IPV production (more than 60 Vero cell culture based runs) to extract relevant information, like operating ranges. Subsequently, based on the MVDA analysis, a 3-L scale-down model of the current twin 750-L bioreactors has been setup. Currently, in this lab-scale process, cell and virus culture approximate the large-scale and process improvement studies are in progress. This includes the application of increased cell densities, animal component free media, and DOE optimization in multiple parallel bioreactors. Also, results will be shown from large-scale (to prepare for future technology transfer) generation and testing of Master- and Working virus seedlots, and clinical lot (for phase I studies) production under cGMP conditions. The obtained product was used for immunogenicity studies in rats. It was shown that Sabin-IPV induces a good immune response, and a comparison will be made to regular Salk-IPV. Finally, technology transfer to vaccine manufacturers in low and middle–income countries will take place. For that, an international Sabin-IPV manufacturing course, including practical training at pilot-scale, is being setup

Hierarchically coupled ultradian oscillators generating robust circadian rhythms

Ensembles of mutually coupled ultradian cellular oscillators have been proposed by a number of authors to explain the generation of circadian rhythms in mammals. Most mathematical models using many coupled oscillators predict that the output period should vary as the square root of the number of participating units, thus being inconsistent with the well-established experimental result that ablation of substantial parts of the suprachiasmatic nuclei (SCN), the main circadian pacemaker in mammals, does not eliminate the overt circadian functions, which show no changes in the phases or periods of the rhythms. From these observations, we have developed a theoretical model that exhibits the robustness of the circadian clock to changes in the number of cells in the SCN, and that is readily adaptable to include the successful features of other known models of circadian regulation, such as the phase response curves and light resetting of the phase

Phase-Induced (In)-Stability in Coupled Parametric Oscillators

We report results on a model of two coupled oscillators that undergo periodic parametric modulations with a phase difference $\theta$. Being to a large extent analytically solvable, the model reveals a rich $\theta$ dependence of the regions of parametric resonance. In particular, the intuitive notion that anti-phase modulations are less prone to parametric resonance is confirmed for sufficiently large coupling and damping. We also compare our results to a recently reported mean field model of collective parametric instability, showing that the two-oscillator model can capture much of the qualitative behavior of the infinite system.Comment: 19 pages, 8 figures; a version with better quality figures can be found in http://hypatia.ucsd.edu/~mauro/English/publications.htm