Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia

The kallikreins and kallikrein-related peptidases are serine proteases that control a plethora of developmental and homeostatic phenomena, ranging from semen liquefaction to skin desquamation and blood pressure. The diversity of roles played by kallikreins has stimulated considerable interest in these enzymes from the perspective of diagnostics and drug design. Kallikreins already have well-established credentials as targets for therapeutic intervention and there is increasing appreciation of their potential both as biomarkers and as targets for inhibitor design. Here, we explore the current status of naturally occurring kallikrein protease-inhibitor complexes and illustrate how this knowledge can interface with strategies for rational re-engineering of bioscaffolds and design of small-molecule inhibitors.

Unsteady natural convection in a triangular enclosure under isothermal heating

The fluid flow and heat transfer inside a triangular enclosure due to instantaneous heating on the inclined walls are investigated using an improved scaling analysis and direct numerical simulations. The development of the unsteady natural convection boundary layer under the inclined walls may be classified into three distinct stages including a start-up stage, a transitional stage and a steady state stage, which can be clearly identified in the analytical and numerical results. A new triple-layer integral approach of scaling analysis has been considered to obtain major scaling relations of the velocity, thicknesses, Nusselt number and the flow development time of the natural convection boundary layer and verified by direct numerical simulations over a wide range of flow parameters.

Scaling of natural convection of an inclined flat plate : ramp cooling condition

A scaling analysis is performed for the transient boundary layer established adjacent to an inclined flat plate following a ramp cooling boundary condition. The imposed wall temperature decreases linearly up to a specific value over a specific time. It is revealed that if the ramp time is sufficiently large then the boundary layer reaches quasi-steady mode before the growth of the temperature is finished. However, if the ramp time is shorter then the steady state of the boundary layer may be reached after the growth of the temperature is completed. In this case, the ultimate steady state is the same as if the start up had been instantaneous. Note that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value for this cooling case. The onset of instability may set in at different stages of the boundary layer development. A proper identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is presented in this study. Different flow regimes based on the stability of the boundary layer have also been discussed with numerical results.

Natural convection boundary-layer adjacent to an inclined flat plate subject to sudden and ramp heating

The natural convection thermal boundary layer adjacent to an inclined flat plate subject to sudden heating and a temperature boundary condition which follows a ramp function up until a specified time and then remains constant is investigated. The development of the flow from start-up to a steady-state has been described based on scaling analyses and verified by numerical simulations. Different flow regimes based on the Rayleigh number are discussed with numerical results for both boundary conditions. For ramp heating, the boundary layer flow depends on the comparison of the time at which the ramp heating is completed and the time at which the boundary layer completes its growth. If the ramp time is long compared with the steady state time, the layer reaches a quasi steady mode in which the growth of the layer is governed solely by the thermal balance between convection and conduction. On the other hand, if the ramp is completed before the layer becomes steady; the subsequent growth is governed by the balance between buoyancy and inertia, as for the case of instantaneous heating.

Scaling of natural convection of an inclined flat plate : sudden cooling condition

The natural convection boundary layer adjacent to an inclined plate subject to sudden cooling boundary condition has been studied. It is found that the cold boundary layer adjacent to the plate is potentially unstable to Rayleigh-Bénard instability if the Rayleigh number exceeds a certain critical value. A scaling relation for the onset of instability of the boundary layer is achieved. The scaling relations have been developed by equating important terms of the governing equations based on the development of the boundary layer with time. The flow adjacent to the plate can be classified broadly into a conductive, a stable convective or an unstable convective regime determined by the Rayleigh number. Proper scales have been established to quantify the flow properties in each of these flow regimes. An appropriate identification of the time when the instability may set in is discussed. A numerical verification of the time for the onset of instability is also presented in this study. Different flow regimes based on the stability of the boundary layer have been discussed with numerical results.

Natural convection in attic-shaped spaces subject to sudden and ramp heating boundary conditions

In this study, a discussion of the fluid dynamics in the attic space is reported, focusing on its transient response to sudden and linear changes of temperature along the two inclined walls. The transient behaviour of an attic space is relevant to our daily life. The instantaneous and non-instantaneous (ramp) heating boundary condition is applied on the sloping walls of the attic space. A theoretical understanding of the transient behaviour of the flow in the enclosure is performed through scaling analysis. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the heating-up of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection in attics subject to instantaneous and ramp cooling boundary conditions

A fundamental study of the fluid dynamics inside an attic shaped triangular enclosure with cold upper walls and adiabatic horizontal bottom wall is reported in this study. The transient behaviour of the attic fluid which is relevant to our daily life is examined based on a scaling analysis. The transient phenomenon begins with the instantaneous cooling and the cooling with linear decreases of temperature up to some specific time (ramp time) and then maintain constant of the upper sloped walls. It is shown that both inclined walls develop a thermal boundary layer whose thicknesses increase towards steady-state or quasi-steady values. A proper identification of the timescales, the velocity and the thickness relevant to the flow that develops inside the cavity makes it possible to predict theoretically the basic flow features that will survive once the thermal flow in the enclosure reaches a steady state. A time scale for the cooling-down of the whole cavity together with the heat transfer scales through the inclined walls has also been obtained through scaling analysis. All scales are verified by the numerical simulations.

Natural convection and heat transfer in attics subject to periodic thermal forcing

The heat transfer through the attics of buildings under realistic thermal forcing has been considered in this study. A periodic temperature boundary condition is applied on the sloping walls of the attic to show the basic flow features in the attic space over diurnal cycles. The numerical results reveal that, during the daytime heating stage, the flow in the attic space is stratified; whereas at the night-time cooling stage, the flow becomes unstable. A symmetrical solution is seen for relatively low Rayleigh numbers. However, as the Ra gradually increases, a transition occurs at a critical value of Ra. Above this critical value, an asymmetrical solution exhibiting a pitchfork bifurcation arises at the night-time. It is also found that the calculated heat transfer rate at the night-time cooling stage is much higher than that during the daytime heating stage.

Radiation effects on natural convection laminar flow from a horizontal circular cylinder

The effect of radiation on natural convection flow from an isothermal circular cylinder has been investigated numerically in this study. The governing boundary layer equations of motion are transformed into a non-dimensional form and the resulting nonlinear systems of partial differential equations are reduced to convenient boundary layer equations, which are then solved numerically by two distinct efficient methods namely: (i) implicit finite differencemethod or the Keller-Box Method (KBM) and (ii) Straight Forward Finite Difference Method (SFFD). Numerical results are presented by velocity and temperature distribution of the fluid as well as heat transfer characteristics, namely the shearing stress and the local heat transfer rate in terms of the local skin-friction coefficient and the local Nusselt number for a wide range of surface heating parameter and radiation-conduction parameter. Due to the effects of the radiation the skin-friction coefficients as well as the rate of heat transfer increased and consequently the momentum and thermal boundary layer thickness enhanced.

The effect of temperature dependent viscosity on MHD natural convection flow from an isothermal sphere

Laminar magnetohydrodynamic (MHD) natural convection flow from an isothermal sphere immersed in a fluid with viscosity proportional to linear function of temperature has been studied. The governing boundary layer equations are transformed into a non-dimensional form and the resulting nonlinear system of partial differential equations are reduced to convenient form which are solved numerically by two very efficient methods, namely, (i) Implicit finite difference method together with Keller box scheme and (ii) Direct numerical scheme. Numerical results are presented by velocity and temperature distribution, streamlines and isotherms of the fluid as well as heat transfer characteristics, namely the local skin-friction coefficients and the local heat transfer rate for a wide range of magnetohydrodynamic paramagnet and viscosity-variation parameter.