Double-stranded flanking ends affect the folding kinetics and conformational equilibrium of G-quadruplexes forming sequences within the promoter of KIT oncogene

G-quadruplexes embedded within promoters play a crucial role in regulating the gene expression. KIT is a widely studied oncogene, whose promoter contains three G-quadruplex forming sequences, c-kit1, c-kit2 and c-kit*. For these sequences available studies cover ensemble and single-molecule analyses, although for kit* the latter were limited to a study on a promoter domain comprising all of them. Recently, c-kit2 has been reported to fold according to a multi-step process involving folding intermediates. Here, by exploiting fluorescence resonance energy transfer, both in ensemble and at the single molecule level, we investigated the folding of expressly designed constructs in which, alike in the physiological context, either c-kit2 or c-kit* are flanked by double stranded DNA segments. To assess whether the presence of flanking ends at the borders of the G-quadruplex affects the folding, we studied under the same protocols oligonucleotides corresponding to the minimal G-quadruplex forming sequences. Data suggest that addition of flanking ends results in biasing both the final equilibrium state and the folding kinetics. A previously unconsidered aspect is thereby unravelled, which ought to be taken into account to achieve a deeper insight of the complex relationships underlying the fine tuning of the gene-regulatory properties of these fascinating DNA structures.

Importance of Non-Equilibrium Modelling for Compressors

This paper investigates the importance of non-equilibrium boundary layer modelling for three compressor blade geometries, using RANS and high fidelity simulations. We find that capturing non-equilibrium effects in RANS is crucial to capturing the correct boundary-layer loss. This is because the production of turbulence within the non-equilibrium region affects both the loss generation in the non-equilibrium region, but also the final equilibrium state. We show that capturing the correct non-equilibrium behaviour is possible by adapting industry standard models (in this case the k-omega SST model). We show that for the range of cases studied here, non-equilibrium effects can modify the trailing-edge momentum thickness by up to 40 percent, and can change the trailing-edge shape factor from 1.8 to 2.1.

Risk Management of Tank Overflow on Tankers Carrying Multiple Grades of Crude Oil

It is demonstrated that tank overflow can occur on board a tanker ship due to the communication of cargo tanks containing dissimilar grades of crude oil. The fundamental principles, which enable the flow from one tank to another and the overflow from exhaust devices on top of the tanks, are reviewed along with the governing equations. The case is analyzed firstly for two communicating tanks in terms of the final equilibrium state and of the time scale of the effect until equilibrium is established or tank overflow is occurred, considering all geometrical and liquid transfer parameters. Measures are proposed to prevent the effect from being initiated and to mitigate the results of the effect once it is occurred. This necessarily leads to the need to extend the study to three communicating tanks. The final equilibrium state for three, and potentially more, tanks is analyzed, which allows a pragmatic approach as to how the situation should be handled on board a tanker facing a tank overflow due to density differences of multiple cargo grades. An extended and generalized Risk Analysis model is proposed to supplement existing models.

A relation between diffusion, temperature and the cosmological constant

We show that the temperature of a diffusing fluid with the diffusion constant [Formula: see text] in an expanding universe approaches a constant limit [Formula: see text] in its final de Sitter stage characterized by the horizon [Formula: see text] determined by the Hubble constant. If de Sitter surface temperature in the final equilibrium state coincides with the fluid temperature, then the cosmological constant [Formula: see text].

A Geostrophic Adjustment Model of Two Buoyant Fluids

A combination of analytical calculations and laboratory experiments has been used to investigate the geostrophic adjustment of two buoyant fluids having different densities in a third denser ambient fluid. The frontal position, the depth profile, and the horizontal and vertical alignments of the two buoyant fluids at the final equilibrium state are determined by the ratio of the baroclinic Rossby radii of deformation Γ1 = λ31/λ21 and Γ2 = λ32/λ21 and the Burger numbers B1 = λ31/L1 and B2 = λ32/L2 of the two buoyant fluids, where is the baroclinic Rossby radius of deformation between fluids i and j. The buoyant fluids 1 and 2 have densities ρ1 and ρ2 (ρ1 < ρ2), respectively; the ambient denser fluid has density ρ3; g′ is the reduced gravity; H and L are the buoyant fluids’ initial depth and width, respectively; and f is the Coriolis parameter. Laboratory rotating experiments confirmed the analytical prediction of the location of the two fronts. After reaching geostrophic equilibrium, the two buoyant currents align mainly horizontally when the extent of the fronts between fluids 1 and 3 and between fluids 2 and 3 is large compared to the extent of the front between fluids 1 and 2: that is, large values of λ31 and λ32 compared to λ21 or equivalently Γ1 ≫ 1 and Γ2 ≫ 1. Alternatively, if the extent of the fronts between the three fluids is similar (i.e., Γ1 ≈ Γ2 ≈ 1), the buoyant currents align mainly vertically. Furthermore, the Burger number of the lightest fluid B1 controls the distance of the inner front from the coast, while B2 controls the offshore extent of the outer front.

Ostwald´s Rule and the Principle of the Shortest Way

We consider a substance X with two monotropic modifications 1 and 2 of different thermodynamic stability ΔH1 < ΔH2. Ostwald´s rule states that first of all the instable modification 1 crystallizes on cooling down liquid X, which subsequently turns into the stable modification 2. Numerous examples verify this rule, however what is its reason? Ostwald´s rule can be traced back to the principle of the shortest way. We start with Hamilton´s principle and the Euler-Lagrange equation of classical mechanics and adapt it to thermodynamics. Now the relevant variables are the entropy S, the entropy production P = dS/dt, and the time t. Application of the Lagrangian F(S, P, t) leads us to the geodesic line S(t). The system moves along the geodesic line on the shortest way I from its initial non-equilibrium state i of entropy Si to the final equilibrium state f of entropy Sf. The two modifications 1 and 2 take different ways I1 and I2. According to the principle of the shortest way, I1 < I2 is realized in the first step of crystallization only. Now we consider a supercooled sample of liquid X at a temperature T just below the melting point of 1 and 2. Then the change of entropy ΔS1 = Sf 1 - Si 1 on crystallizing 1 can be related to the corresponding chang of enthalpy by ΔS1 = ΔH1/T. Now it can be shown that the shortest way of crystallization I1 corresponds under special, well-defined conditions to the smallest change of entropy ΔS1 < ΔS2 and thus enthalpy ΔH1 < ΔH2. In other words, the shortest way of crystallization I1 really leads us to the instable modification 1. This is Ostwald´s rule.

Integrated chemical–physical processes kinetic modelling of multiple mineral precipitation problems

A three-phase (aqueous/gas/solid) mixed weak acid/base chemistry kinetic model is applied to evaluate the processes operative in the aeration treatment of swine wastewater (SWW) and sewage sludge anaerobic digester liquor (ADL). In both applications, with a single set of constants (except for the aeration rates which are situation specific), close correlation could be obtained between predicted and measured data, except for the Ca concentration–time profile in the SWW. For this wastewater, the model application highlighted an inconsistency in the measured Ca data which could not be resolved; this illustrates the value of a mass balance-based model in evaluating experimental data. From the model applications, in both wastewaters the dominant minerals precipitating are struvite and amorphous calcium phosphate (ACP), which precipitate simultaneously competing for the same species, P. The absolute and relative masses of the two precipitants are governed by the initial solution state (e.g. total inorganic C (CT), Mg, Ca and P concentrations), their relative precipitation rates (struvite &gt; ACP) and the system conditions imposed (aeration rates and time applied). It is concluded that the kinetic model is able to predict correctly the time-dependent weak acid/base chemistry reactions and final equilibrium state for situations where multiple minerals competing for the same species precipitate simultaneously or sequentially, a deficiency in traditional equilibrium chemistry-based algebraic models.

Electrical streaming potential precursors to catastrophic earthquakes in China

The majority of anomalies in self-potential at 7 stations within 160 km from the epicentre showed a similar pattern of rapid onset and slow decay during and before the M 7.8 Tangshan earthquake of 1976. Considering that some of these anomalies associated with episodical spouting from boreholes or the increase in pore pressure in wells, observed anomalies are streaming potential generated by local events of sudden movements and diffusion process of high-pressure fluid in parallel faults. These transient events triggered by tidal forces exhibited a periodic nature and the statistical phenomenon to migrate towards the epicentre about one month before the earthquake. As a result of events, the pore pressure reached its final equilibrium state and was higher than that in the initial state in a large enough section of the fault region. Consequently, local effective shear strength of the material in the fault zone decreased and finally the catastrophic earthquake was induced. Similar phenomena also occurred one month before the M 7.3 Haichen earthquake of 1975. Therefore, a short term earthquake prediction can be made by electrical measurements, which are the kind of geophysical measurements most closely related to pore fluid behaviors of the deep crust.

Taylor-Couette Instability With a Continuous Spectrum

Nonlinear evolution of a continuous spectrum of unstable waves near the first bifurcation point in circular Couette flow has been investigated. The disturbance is represented by a Fourier integral over all possible axial wave numbers, and an integrodif-ferential equation for the amplitude-density function of a continuous spectrum is derived. The equations describing the evolution of monochromatic waves and slowly varying wave packets of classical weakly nonlinear instability theories are shown to be special limiting cases. Numerical integration of the integrodifferential equation shows that the final equilibrium state depends on the initial disturbance, as observed experimentally, and it is not unique. In all cases, the final equilibrium state consists of a single dominant mode and its harmonics of smaller amplitudes. The predicted range of wave numbers for stable supercritical Taylor vortices is found to be narrower than the span of the neutral curve from linear theory. Taylor-vortex flows with wave numbers outside this range are found to be unstable and to decay, but to excite another wave inside the narrow band. This result is in agreement with the Eckhaus and Benjamin-Feir sideband instability. The results also show that a linearly stable long wave can excite a short unstable wave through nonlinear wave interaction. An important implication of the existence of nonunique equilibrium states is that the torque induced by the fluid motion cannot be determined uniquely. The numerical results show that the uncertainty, associated with nonuniqueness, of using any accurately measured Taylor-vortex torque slightly above the first bifurcation point in engineering practice can be as large as ten percent. The presence of multiple solutions at a fixed Reynolds number for a given geometry in Taylor-Couette flows has been known since Coles’ monumental contribution in 1965. A theoretical confirmation has come only 30 years later. It is worthwhile to point out that the existence of multiple solutions, found by Coles, differs from current popular bifurcation theories. The current study indicates that the state of flows on a stable bifurcation branch can involve any wave number within a finite band and can not be determined uniquely. The multiple solutions in Coles’ sense have also been found for mixed-convection flows (Yao and Ghosh Moulic, 1993, 1994) besides the Taylor-Couette flows. We believe that the nonuniqueness of Coles sense, which complements the bifurcation theories, is a generic property for all fluid flows.