Angelman Syndrome Protein UBE3A Interacts with Primary Microcephaly Protein ASPM, Localizes to Centrosomes and Regulates Chromosome Segregation

Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH) proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly) protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

Solubilities of Pb+2, Bi+3, Sb+3 and Cu+1 sulphides in (NaCl KCl Na2S) melts

Solubilities of common metal sulfides have been determined in the (NaCl+KCl) eutectic melt with and without Na2S. A novel gas-phase equilibrium technique has been used for PbS, Bi2S3, and So2S3, and an improved liquid phase equilibrium technique for Cu2S, which eliminates the errors due to physical entrapment of the sulfide phase and segregation on quenching, enabling precise measurements to be made. Solubilities in the (NaCl+KCl) eutectic melt were determined as a function of temperature in the rante 700° to 950°C, and were found to be small. The partial molar heats of mixing of the sulfides in the eutectic melt have been calculated from the solubility measurements, to be 13.3, 31.4, 37.1, and 49.0 kcal for PbSs), Sb2S2(l), and Cu2S(s), respectively. Sodium sulfide addition was observed to enhance these solubilities, the effect being largest for Cu2S followed by Sb2S3, Bi2S3, and PbS. This effect is explained qualitatively. It was observed that PbS and Sb2S3 obey Henry's law up to saturation in (NaCl+KCl+Na2S) melts.

Heat of Mixing and Activities in Liquid Al-Sn Alloys

The microscopic electron theory based on the pseudopotential formalism has been applied to the calculation of the heats of mixing and of activities in liquid Al·Sn alloys. The calculated values for both quantities were found to be in reasonable agreement with ,the experimental data.

Session 6 grouting and deep mixing: New concept and applications

The theme of the session is the New Concept and Applications both for the grouting and deep mixing technologies. Nineteen papers were submitted to this session, and those covered a variety of topics; 1) New concepts and development, 2) Refinement of techniques, and 3) analysis and applications. Eight papers out of them were presented orally.

A multifold reduction in the transition Reynolds number, and ultra-fast mixing, in a micro-channel due to a dynamical instability induced by a soft wall

A dynamical instability is observed in experimental studies on micro-channels of rectangular cross-section with smallest dimension 100 and 160 mu m in which one of the walls is made of soft gel. There is a spontaneous transition from an ordered, laminar flow to a chaotic and highly mixed flow state when the Reynolds number increases beyond a critical value. The critical Reynolds number, which decreases as the elasticity modulus of the soft wall is reduced, is as low as 200 for the softest wall used here (in contrast to 1200 for a rigid-walled channel) The instability onset is observed by the breakup of a dye-stream introduced in the centre of the micro-channel, as well as the onset of wall oscillations due to laser scattering from fluorescent beads embedded in the wall of the channel. The mixing time across a channel of width 1.5 mm, measured by dye-stream and outlet conductance experiments, is smaller by a factor of 10(5) than that for a laminar flow. The increased mixing rate comes at very little cost, because the pressure drop (energy requirement to drive the flow) increases continuously and modestly at transition. The deformed shape is reconstructed numerically, and computational fluid dynamics (CFD) simulations are carried out to obtain the pressure gradient and the velocity fields for different flow rates. The pressure difference across the channel predicted by simulations is in agreement with the experiments (within experimental errors) for flow rates where the dye stream is laminar, but the experimental pressure difference is higher than the simulation prediction after dye-stream breakup. A linear stability analysis is carried out using the parallel-flow approximation, in which the wall is modelled as a neo-Hookean elastic solid, and the simulation results for the mean velocity and pressure gradient from the CFD simulations are used as inputs. The stability analysis accurately predicts the Reynolds number (based on flow rate) at which an instability is observed in the dye stream, and it also predicts that the instability first takes place at the downstream converging section of the channel, and not at the upstream diverging section. The stability analysis also indicates that the destabilization is due to the modification of the flow and the local pressure gradient due to the wall deformation; if we assume a parabolic velocity profile with the pressure gradient given by the plane Poiseuille law, the flow is always found to be stable.

Structural, thermal and electrical properties of poly(methyl methacrylate)/CaCu3Ti4O12 composite sheets fabricated via melt mixing

Poly(methyl methacrylate) (PMMA) and CaCu3Ti4O12 (CCTO) composites were fabricated via melt mixing followed by hot pressing technique. These were characterized using X-ray diffraction, thermo gravimetric, thermo mechanical, differential scanning calorimetry, fourier transform infrared (FTIR) and Impedance analyser for their structural, thermal and dielectric properties. Composites were found to have better thermal stability than that of pure PMMA. However, there was no significant difference in the glass transition (T (g) ) temperature between the polymer and the composite. The appearance of additional vibrational frequencies in the range 400-600 cm(-1) in FTIR spectra indicated a possible interaction between PMMA and CCTO. The composite, with 38 vol% of CCTO (in PMMA), exhibited remarkably low dielectric loss at high frequencies and the low-frequency relaxation is attributed to the interfacial polarization/MWS effect. The origin of AC conductivity particularly in the high-frequency region was attributed to the electronic polarization.

Periodically Clickable Polyesters: Study of Intrachain Self-Segregation Induced Folding, Crystallization, and Mesophase Formation

A series of polyesters based on 2-propargyl-1,3-propanediol or 2,2-dipropargyl-1,3-propanediol or 2-allyl-2-propargyl-1,3-propanediol and 1,20-eicosanedioic acid were prepared by solution polycondensation using the corresponding diacid chloride; these polyesters were quantitatively ``clicked'' with a fluoroalkyl, azide, namely CF3(CF2)(7)CH2CH2N3, to yield polyesters carrying long-chain alkylene segments in the backbone and either one or two perfluoroalkyl segments located at periodic intervals along the polymer chain. The immiscibility of the alkylene and fluoroalkyl segments causes the polymer chains to fold in a zigzag fashion to facilitate the segregation of these segments; the folded chains further organize in the solid state to form a lamellar structure with alternating domains of alkyl (HC) and fluoroalkyl (FC) segments. Evidence for the self-segregation is provided by DSC, SAXS, WAXS, and TEM studies; in two of the samples, the DSC thermograms showed two distinct endotherms associated with the melting of the individual domains, while the WAXS patterns confirm the existence of two separate peaks corresponding to the interchain distances within the crystalline lattices of the HC and FC domains. SAXS data, on the other hand, reveal the formation of an extended lamellar morphology with an interlamellar spacing that matches reasonably well with those estimated from TEM studies. Interestingly, a smectic-type liquid crystalline phase is observed at temperatures between the two melting transitions. These systems present a unique opportunity to develop interesting nanostructured polymeric materials with precise control over both the domain size and morphology; importantly, the domain sizes are far smaller than those typically observed in traditional block copolymers.

Optical diagnostics of fuel-air mixing and vortex formation in a cavity combustor

The current work reports optical diagnostic measurements of fuel-air mixing and vortex structure in a single cavity trapped vortex combustor (TVC). Specifically, the mixture fraction using acetone PLIF technique in the non-reacting flow, and PIV measurements in the reacting flow are reported for the first time in trapped vortex combustors. The fuel-air momentum flux ratio, where the air momentum corresponds to that entering the cavity through a specially-incorporated flow guide vane, is used to characterize the mixing. The acetone PLIF experiments show that at high momentum flux ratios, the fuel-air mixing in the cavity is very minimal and is enhanced as the momentum flux ratio reduces, due to a favourable vortex formation in the cavity. Stoichiometric mixture fraction surfaces show that the mixing causes the reaction surfaces to shift from non-premixed to partially-premixed stratified mixtures. PIV measurements conducted in the non-reacting flow in the cavity further reinforce this observation. The scalar dissipation rates of mixture fraction were compared with the contours of RMS of fluctuating velocity and showed very good agreement. The regions of maximum mixing are observed to be along the fuel air interface. Reacting flow Ply measurements which differ substantially from the non-reacting cases primarily because of the heat release from combustion and the resulting gas expansion show that the vortex is displaced from the centre of the cavity towards the guide vane. Overall, the measurements show interesting features of the flow including the presence of the dual cavity structure and lead to a clear understanding of the underlying physics of the cavity flow highlighting the importance of the fuel-air momentum ratio parameter. (C) 2014 Elsevier Inc. All rights reserved.

Diurnal and seasonal variation of mixing ratio and delta C-13 of air CO2 observed at an urban station Bangalore, India

We present here observations on diurnal and seasonal variation of mixing ratio and delta C-13 of air CO2, from an urban station-Bangalore (BLR), India, monitored between October 2008 and December 2011. On a diurnal scale, higher mixing ratio with depleted delta C-13 of air CO2 was found for the samples collected during early morning compared to the samples collected during late afternoon. On a seasonal scale, mixing ratio was found to be higher for dry summer months (April-May) and lower for southwest monsoon months (June-July). The maximum enrichment in delta C-13 of air CO2 (-8.04 +/- 0.02aEuro degrees) was seen in October, then delta C-13 started depleting and maximum depletion (-9.31 +/- 0.07aEuro degrees) was observed during dry summer months. Immediately after that an increasing trend in delta C-13 was monitored coincidental with the advancement of southwest monsoon months and maximum enrichment was seen again in October. Although a similar pattern in seasonal variation was observed for the three consecutive years, the dry summer months of 2011 captured distinctly lower amplitude in both the mixing ratio and delta C-13 of air CO2 compared to the dry summer months of 2009 and 2010. This was explained with reduced biomass burning and increased productivity associated with prominent La Nina condition. While compared with the observations from the nearest coastal and open ocean stations-Cabo de Rama (CRI) and Seychelles (SEY), BLR being located within an urban region captured higher amplitude of seasonal variation. The average delta C-13 value of the end member source CO2 was identified based on both diurnal and seasonal scale variation. The delta C-13 value of source CO2 (-24.9 +/- 3aEuro degrees) determined based on diurnal variation was found to differ drastically from the source value (-14.6 +/- 0.7aEuro degrees) identified based on seasonal scale variation. The source CO2 identified based on diurnal variation incorporated both early morning and late afternoon sample; whereas, the source CO2 identified based on seasonal variation included only afternoon samples. Thus, it is evident from the study that sampling timing is one of the important factors while characterizing the composition of end member source CO2 for a particular station. The difference in delta C-13 value of source CO2 obtained based on both diurnal and seasonal variation might be due to possible contribution from cement industry along with fossil fuel / biomass burning as predominant sources for the station along with differential meteorological conditions prevailed.

Reynolds averaged Navier-Stokes simulations of compressible mixing layers of similar and dissimilar gases: Performance of k- turbulence model

The issue of growth rate reduction of high speed mixing layer with convective Mach number is examined for similar and dissimilar gases using Reynolds averaged Navier-Stokes (RANS) methodology with k- turbulence model. It is observed that the growth rate predicted using RANS simulations closely matches with that predicted using model free simulations. Velocity profiles do not depend on the modelled value of Pr-t and Sc-t; while the temperature and species mass fraction distributions depend heavily on them. Although basic k- turbulence model could not capture the reduced growth rate for the mixing layer formed between similar gases, it predicts very well the reduced growth rate for the mixing layer for the dissimilar gases. It appears that density ratio changes caused by temperature changes for the dissimilar gases have profound effect on the growth rate reduction.

Direct numerical simulation of transition and turbulence in compressible mixing layer

The three-dimensional compressible Navier-Stokes equations are approximated by a fifth order upwind compact and a sixth order symmetrical compact difference relations combined with three-stage Ronge-Kutta method. The computed results are presented for convective Mach number Mc = 0.8 and Re = 200 with initial data which have equal and opposite oblique waves. From the computed results we can see the variation of coherent structures with time integration and full process of instability, formation of Lambda-vortices, double horseshoe vortices and mushroom structures. The large structures break into small and smaller vortex structures. Finally, the movement of small structure becomes dominant, and flow field turns into turbulence. It is noted that production of small vortex structures is combined with turning of symmetrical structures to unsymmetrical ones. It is shown in the present computation that the flow field turns into turbulence directly from initial instability and there is not vortex pairing in process of transition. It means that for large convective Mach number the transition mechanism for compressible mixing layer differs from that in incompressible mixing layer.

A comparison of winter pre-heating requirements for natural displacement and natural mixing ventilation

In winter, natural ventilation can be achieved either through mixing ventilation or upward displacement ventilation (P.F. Linden, The fluid mechanics of natural ventilation, Annual Review of Fluid Mechanics 31 (1999) pp. 201-238). We show there is a significant energy saving possible by using mixing ventilation, in the case that the internal heat gains are significant, and illustrate these savings using an idealized model, which predicts that with internal heat gains of order 0.1 kW per person, mixing ventilation uses of a fraction of order 0.2-0.4 of the heat load of displacement ventilation assuming a well-insulated building. We then describe a strategy for such mixing natural ventilation in an atrium style building in which the rooms surrounding the atrium are able to vent directly to the exterior and also through the atrium to the exterior. The results are motivated by the desire to reduce the energy burden in large public buildings such as hospitals, schools or office buildings centred on atria. We illustrate a strategy for the natural mixing ventilation in order that the rooms surrounding the atrium receive both pre-heated but also sufficiently fresh air, while the central atrium zone remains warm. We test the principles with some laboratory experiments in which a model air chamber is ventilated using both mixing and displacement ventilation, and compare the energy loads in each case. We conclude with a discussion of the potential applications of the approach within the context of open plan atria type office buildings.

Behaviour analysis of numerical solutions and simulation of coherent structures in compressible mixing layers

For understanding the correctness of simulations the behaviour of numerical solutions is analysed, Tn order to improve the accuracy of solutions three methods are presented. The method with GVC (group velocity control) is used to simulate coherent structures in compressible mixing layers. The effect of initial conditions for the mixing layer with convective Mach number 0.8 on coherent structures is discussed. For the given initial conditions two types of coherent structures in the mixing layer are obtained.