Soret and Dufour effects on mixed convection in a non-Darcy porous medium saturated with micropolar fluid

In this paper, the Soret and Dufour effects on the steady, laminar mixed convection heat and mass transfer along a semi-infinite vertical plate embedded in a non-Darcy porous medium saturated with micropolar fluid are studied. The governing partial differential equations are transformed into ordinary differential equations. The local similarity solutions of the transformed dimensionless equations for the flow, microrotation, heat and mass transfer characteristics are evaluated using Keller-box method. Numerical results are presented in the form of velocity, microrotation, temperature and concentration profiles within the boundary layer for different parameters entering into the analysis. Also the effects of the pertinent parameters on the local skin friction coefficient and rates of heat and mass transfer in terms of the local Nusselt and Sherwood numbers are also discussed

Third Hankel determinant for starlike and convex functions with respect to symmetric points

The objective of this paper is to obtain best possible upper bound to the $H_{3}(1)$  Hankel determinant for starlike and convex functions with respect to symmetric points, using Toeplitz determinants

Coefficient inequality for transforms of certain subclass of analytic functions

The objective of this paper is to obtain the best possible sharp upper bound for the second Hankel functional associated with the kth root transform [f(zk)]1/k of normalized analytic function f(z) when it belongs to certain subclass of analytic functions, defined on the open unit disc in the complex plane using Toeplitz determinants

An upper bound to the second Hankel determinant for pre-starlike functions of order α

The objective of this paper is to obtain an upper bound to the second Hankel determinant  for the function f and its inverse belonging to the class of pre-starlike functions of order alpha (0 ≤ alpha ≤ 1), using Toeplitz determinants

DNA cruciform arms nucleate through a correlated but non-synchronous cooperative mechanism

Inverted repeat (IR) sequences in DNA can form non-canonical cruciform structures to relieve torsional stress. We use Monte Carlo simulations of a recently developed coarse-grained model of DNA to demonstrate that the nucleation of a cruciform can proceed through a cooperative mechanism. Firstly, a twist-induced denaturation bubble must diffuse so that its midpoint is near the centre of symmetry of the IR sequence. Secondly, bubble fluctuations must be large enough to allow one of the arms to form a small number of hairpin bonds. Once the first arm is partially formed, the second arm can rapidly grow to a similar size. Because bubbles can twist back on themselves, they need considerably fewer bases to resolve torsional stress than the final cruciform state does. The initially stabilised cruciform therefore continues to grow, which typically proceeds synchronously, reminiscent of the S-type mechanism of cruciform formation. By using umbrella sampling techniques we calculate, for different temperatures and superhelical densities, the free energy as a function of the number of bonds in each cruciform along the correlated but non-synchronous nucleation pathways we observed in direct simulations.Comment: 12 pages main paper + 11 pages supplementary dat

Real-time detection of cruciform extrusion by single-molecule DNA nanomanipulation

During cruciform extrusion, a DNA inverted repeat unwinds and forms a four-way junction in which two of the branches consist of hairpin structures obtained by self-pairing of the inverted repeats. Here, we use single-molecule DNA nanomanipulation to monitor in real-time cruciform extrusion and rewinding. This allows us to determine the size of the cruciform to nearly base pair accuracy and its kinetics with second-scale time resolution. We present data obtained with two different inverted repeats, one perfect and one imperfect, and extend single-molecule force spectroscopy to measure the torque dependence of cruciform extrusion and rewinding kinetics. Using mutational analysis and a simple two-state model, we find that in the transition state intermediate only the B-DNA located between the inverted repeats (and corresponding to the unpaired apical loop) is unwound, implying that initial stabilization of the four-way (or Holliday) junction is rate-limiting. We thus find that cruciform extrusion is kinetically regulated by features of the hairpin loop, while rewinding is kinetically regulated by features of the stem. These results provide mechanistic insight into cruciform extrusion and help understand the structural features that determine the relative stability of the cruciform and B-form states

The release and trans-synaptic transmission of Tau via exosomes

BACKGROUND Tau pathology in AD spreads in a hierarchical pattern, whereby it first appears in the entorhinal cortex, then spreads to the hippocampus and later to the surrounding areas. Based on this sequential appearance, AD can be classified into six stages ("Braak stages"). The mechanisms and agents underlying the progression of Tau pathology are a matter of debate. Emerging evidence indicates that the propagation of Tau pathology may be due to the transmission of Tau protein, but the underlying pathways and Tau species are not well understood. In this study we investigated the question of Tau spreading via small extracellular vesicles called exosomes. METHODS Exosomes from different sources were analyzed by biochemical methods and electron microscopy (EM) and cryo-EM. Microfluidic devices that allow the culture of cell populations in different compartments were used to investigate the spreading of Tau. RESULTS We show that Tau protein is released by cultured primary neurons or by N2a cells overexpressing different Tau constructs via exosomes. Neuron-derived exosomal Tau is hypo-phosphorylated, compared with cytosolic Tau. Depolarization of neurons promotes release of Tau-containing exosomes, highlighting the importance of neuronal activity. Using microfluidic devices we show that exosomes mediate trans-neuronal transfer of Tau depending on synaptic connectivity. Tau spreading is achieved by direct transmission of exosomes between neurons. In organotypic hippocampal slices, Tau-containing exosomes in conditioned medium are taken up by neurons and microglia, not astrocytes. In N2a cells, Tau assemblies are released via exosomes. They can induce inclusions of other Tau molecules in N2a cells expressing mutant human Tau. We also studied exosomes from cerebrospinal fluid in AD and control subjects containing monomeric and oligomeric Tau. Split-luciferase complementation reveals that exosomes from CSF can promote Tau aggregation in cultured cells. CONCLUSION Our study demonstrates that exosomes contribute to trans-synaptic Tau transmission, and thus offer new approches to control the spreading of pathology in AD and other tauopathies