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Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Dissecting Representations

Choosing effective representations for a problem and for the person solving it has benefits, including the ability or inability to solve it. We previously devised a novel framework consisting of a language to describe representations and computational methods to analyse them in terms of their formal and cognitive properties. In this paper we demonstrate the application of this framework to a variety of notations including natural languages, formal languages, and diagrams. We show how our framework, and the analysis of representations that it enables, gives us insight into how and why we can select representations which are appropriate for both the task and the user

Heavy-to-light baryonic form factors at large recoil

We analyze heavy-to-light baryonic form factors at large recoil and derive the scaling behavior of these form factors in the heavy quark limit. It is shown that only one universal form factor is needed to parameterize Lambda_b to p and Lambda_b to Lambda matrix elements in the large recoil limit of light baryons, while hadronic matrix elements of Lambda_b to Sigma transition vanish in the large energy limit of Sigma baryon due to the space-time parity symmetry. The scaling law of the soft form factor eta(P^{\prime} \cdot v), P^{\prime} and v being the momentum of nucleon and the velocity of Lambda_b baryon, responsible for Lambda_b to p transitions is also derived using the nucleon distribution amplitudes in leading conformal spin. In particular, we verify that this scaling behavior is in full agreement with that from light-cone sum rule approach in the heavy-quark limit. With these form factors, we further investigate the Lambda baryon polarization asymmetry alpha in Lambda_b to Lambda gamma and the forward-backward asymmetry A_{FB} in Lambda_b to Lambda l^{+} l^{-}. Both two observables (alpha and A_{FB}) are independent of hadronic form factors in leading power of 1/m_b and in leading order of alpha_s. We also extend the analysis of hadronic matrix elements for Omega_b to Omega transitions to rare Omega_b to Omega gamma and Omega_b to Omega l^{+} l^{-} decays and find that radiative Omega_b to Omega gamma decay is probably the most promising FCNC b to s radiative baryonic decay channel. In addition, it is interesting to notice that the zero-point of forward-backward asymmetry of Omega_b to Omega l^{+} l^{-} is the same as the one for Lambda_b to Lambda l^{+} l^{-} to leading order accuracy provided that the form factors \bar{\zeta}_i (i=3, 4, 5) are numerically as small as indicated from the quark model.Comment: 19 page

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

On CP Asymmetries in Two-, Three- and Four-Body D Decays

Indirect and direct CP violations have been established in K_L and B_d decays. They have been found in two-body decay channels -- with the exception of K_L to pi^+ pi^- e^+ e^- transitions. Evidence for direct CP asymmetry has just appeared in LHCb data on A_{CP}(D^0 to K^+ K^-) - A_{CP}(D^0 to pi^+ pi^-) with 3.5 sigma significance. Manifestations of New Dynamics (ND) can appear in CP asymmetries just below experimental bounds. We discuss D^{\pm}_{(s)}, D^0/\bar D^0 and D_L/D_S transitions to 2-, 3- and 4-body final states with a comment on predictions for inclusive vs. exclusive CP asymmetries. In particular we discuss T asymmetries in D to h_1 h_2 l^+ l^- in analogy with K_L to pi^+ pi^- e^+ e^- transitions due to interference between M1, internal bremsstrahlung and possible E1 amplitudes. Such an effect depends on the strength of CP violation originating from the ND -- as discussed here for Little Higgs Models with T parity and non-minimal Higgs sectors -- but also in the interferences between these amplitudes even in the Standard Model (SM). More general lessons can be learnt for T asymmetries in non-leptonic D decays like D to h_1h_2 h_3 h_4. Such manifestations of ND can be tested at LHCb and other Super-Flavour Factories like the projects at KEK near Tokyo and at Tor Vergata/Frascati near Rome.Comment: 27 pages, 6 figures. Revised with current results from LHCb and HFAG and further interpretation

Choosing the Best Direction of Printing for Additive Manufacturing Process in Medical Applications Using a New Geometric Complexity Model Based on Part CAD Data

Additive manufacturing processes is now experiencing significant growth and is at the origin of intense research activity (optimization of topology, biomedical applications, etc.). One of the characteristics of this method is that the geometric complexity is free. The complexity of a CAD model is also a field of research. The basic idea is that the complexity of a component has implications in design and especially in manufacturing. Indeed, industrial competitiveness in the mechanical field generated the need to produce increasingly complex systems and parts (in terms of geometry, topology ...). Part deposition orientation is also very important factor of additive manufacturing as it effects build time, support structure, dimensional accuracy, surface finish and cost of the part. A number of layered manufacturing process specific parameters and constraints have to be considered while deciding the part deposition orientation. Determination of an optimal part deposition orientation is a difficult and time consuming task as one has to trade-off among various contradicting objectives like part surface finish and build time. This paper describes and compares various attempts made to determine part deposition orientation of orthoses using geometric complexity model and part CAD information. (c) Springer Nature Switzerland AG 2019

A consistent picture for large penguins in D -> pi+ pi-, K+ K-

A long-standing puzzle in charm physics is the large difference between the D0 -> K+ K- and D0 -> pi+ pi- decay rates. Recently, the LHCb and CDF collaborations reported a surprisingly large difference between the direct CP asymmetries, Delta A_CP, in these two modes. We show that the two puzzles are naturally related in the Standard Model via s- and d-quark "penguin contractions". Their sum gives rise to Delta A_CP, while their difference contributes to the two branching ratios with opposite sign. Assuming nominal SU(3) breaking, a U-spin fit to the D0 -> K+ pi-, pi+ K-, pi+ pi-, K+ K- decay rates yields large penguin contractions that naturally explain Delta A_CP. Expectations for the individual CP asymmetries are also discussed.Comment: 24 pages, 8 figure

Spin-orbit density wave induced hidden topological order in URu2Si2

The conventional order parameters in quantum matters are often characterized by 'spontaneous' broken symmetries. However, sometimes the broken symmetries may blend with the invariant symmetries to lead to mysterious emergent phases. The heavy fermion metal URu2Si2 is one such example, where the order parameter responsible for a second-order phase transition at Th = 17.5 K has remained a long-standing mystery. Here we propose via ab-initio calculation and effective model that a novel spin-orbit density wave in the f-states is responsible for the hidden-order phase in URu2Si2. The staggered spin-orbit order 'spontaneous' breaks rotational, and translational symmetries while time-reversal symmetry remains intact. Thus it is immune to pressure, but can be destroyed by magnetic field even at T = 0 K, that means at a quantum critical point. We compute topological index of the order parameter to show that the hidden order is topologically invariant. Finally, some verifiable predictions are presented.Comment: (v2) Substantially modified from v1, more calculation and comparison with experiments are include

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio