Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting

PURPOSE: To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting. METHODS: A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis. RESULTS: TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60+/-0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles). CONCLUSIONS: Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake

Novel pharmacological actions of Trequinsin Hydrochloride improve human sperm cell motility and function

Background and purposeAsthenozoospermia is a leading cause of male infertility, but the development of pharmaceuticals to improve sperm motility has been hindered by the lack of effective screening platforms and knowledge of suitable molecular targets. We have demonstrated that a high throughput screening (HTS) strategy in conjunction with established in vitro tests can identify and characterise the action of compounds that improve sperm motility. The study aimed to apply HTS to identify new compounds from a novel small molecule library that increase intracellular calcium, [Ca2+]I, promote human sperm cell motility and systemically determine the mechanism of action. Experimental approach A validated HTS fluorometric [Ca2+]i assay was used to screen an in-house library of compounds. Trequinsin hydrochloride (a phosphodiesterase 3 inhibitor) was selected for detailed molecular (plate reader assays, electrophysiology and cyclic nucleotide measurement) and functional (motility and acrosome reaction) testing in sperm from healthy volunteer donors and, where possible, patients.   Key resultsThe fluorometric analysis identified Trequinsin as an efficacious agonist of [Ca2+]i, although less potent than progesterone (P4). Functionally, Trequinsin significantly increased cell hyperactivation and penetration into viscous medium in all donor sperm samples and cell hyperactivation in 22/25 (88%) patient sperm samples. The Trequinsin-induced [Ca2+]i response was cross-desensitised consistently by prostaglandin E1 but not with P4. Whole-cell patch clamp electrophysiology confirmed that Trequinsin activates CatSper and partially inhibits potassium channel activity. Trequinsin also increases intracellular cGMP.   Conclusion and Implications Trequinsin exhibits a novel pharmacological profile in human sperm and may be a suitable lead compound for the development of new pharmaceuticals to improve patient sperm function and fertilisation potential

Computation with narrow CTCs

We examine some variants of computation with closed timelike curves (CTCs), where various restrictions are imposed on the memory of the computer, and the information carrying capacity and range of the CTC. We give full characterizations of the classes of languages recognized by polynomial time probabilistic and quantum computers that can send a single classical bit to their own past. Such narrow CTCs are demonstrated to add the power of limited nondeterminism to deterministic computers, and lead to exponential speedup in constant-space probabilistic and quantum computation. We show that, given a time machine with constant negative delay, one can implement CTC-based computations without the need to know about the runtime beforehand.Comment: 16 pages. A few typo was correcte

HQET chromomagnetic interaction at two loops

We present the coefficient of the chromomagnetic interaction operator, the only unknown coefficient in the Heavy Quark Effective Theory (HQET) lagrangian up to the $1/m$ level, with the two-loop accuracy by matching scattering amplitudes of an on-shell heavy quark in an external field in full QCD and HQET, and obtain the two-loop anomalous dimension of this operator in HQET.Comment: 10 pages, LaTeX2e, 2 eps figures included. Revised discussion of (n_f-1)-flavour HQET include

Two-loop renormalization of the effective field theory of a static quark

We give a recurrence relation for two-loop integrals encountered in the effective field theory of an infinitely heavy quark, Q, interacting with gluons and Nl massless quarks, q, from which we obtain exact two-loop results, in any dimension and covariant gauge, for the propagator of Q and the vertex function of the heavy-light current J = Q Gamma q, at zero q momentum. The anomalous dimension of the Q field agrees with the recent result of Broadhurst, Gray and Schilcher. The anomalous dimension of the current is gamma_J = d log Z_J / d log mu = - alpha_s/pi (1 + (127 + 56 zeta(2) - 10 Nl)/72) alpha_s/pi + O(alpha_s^2)) which gives the new two-loop correction to the result of Voloshin and Shifman.Comment: Old preprin

An application of interpolating scaling functions to wave packet propagation

Wave packet propagation in the basis of interpolating scaling functions (ISF) is studied. The ISF are well known in the multiresolution analysis based on spline biorthogonal wavelets. The ISF form a cardinal basis set corresponding to an equidistantly spaced grid. They have compact support of the size determined by the underlying interpolating polynomial that is used to generate ISF. In this basis the potential energy matrix is diagonal and the kinetic energy matrix is sparse and, in the 1D case, has a band-diagonal structure. An important feature of the basis is that matrix elements of a Hamiltonian are exactly computed by means of simple algebraic transformations efficiently implemented numerically. Therefore the number of grid points and the order of the underlying interpolating polynomial can easily be varied allowing one to approach the accuracy of pseudospectral methods in a regular manner, similar to high order finite difference methods. The results of numerical simulations of an H+H_2 collinear collision show that the ISF provide one with an accurate and efficient representation for use in the wave packet propagation method.Comment: plain Latex, 11 pages, 4 figures attached in the JPEG forma

Short-pulse, extreme-ultraviolet continuum emission from a table-top laser plasma light source

We have observed extreme-ultraviolet (XUV) “line-free” continuum emission from laser plasmas of high atomic number elements using targets irradiated with 248 nm laser pulses of 7 ps duration at a power density of ∼ 1013 W/cm2. Using both dispersive spectroscopy and streak camera detection, the spectral and temporal evolution of XUV continuum emission for several target atomic numbers has been measured on a time scale with an upper limit of several hundred picoseconds limited by amplified spontaneous emission

Three-Loop Chromomagnetic Interaction in HQET

We compute the three-loop QCD corrections to the quark chromomagnetic moment and thus obtain the matching coefficient and the anomalous dimension of the chromomagnetic interaction in HQET. As a byproduct we obtain the three-loop corrections to the quark anomalous magnetic moment.Comment: 22 page

Asymptotics of the perturbative series for f_{B^*}/f_B

We investigate the structure of the leading IR renormalon singularity in the QCD/HQET matching coefficients for heavy-light quark currents beyond the large-\beta_0 limit. From this result, we derive the large-order behaviour of the perturbative series for these coefficients, and for ratios of meson matrix elements, such as f_{B^*}/f_B.Comment: 45 pages, 2 eps figures. v2: small corrections, reference added. v3: reference added. v4: errors in some equations of Appendix B, in (5.8) and Table 2 corrected, numerical changes are very small. Paper also available from http://www-ttp.physik.uni-karlsruhe.de/Preprints