A-Stability and Stochastic Mean-Square Stability

This note extends and interprets a result of Saito and Mitsui [SIAM J. Numer. Anal., 33 (1996), pp. 2254–2267] for a method of Milstein. The result concerns mean-square stability on a stochastic differential equation test problem with multiplicative noise. The numerical method reduces to the Theta Method on deterministic problems. Saito and Mitsui showed that the deterministic A-stability property of the Theta Method does not carry through to the mean-square context in general, and gave a condition under which unconditional stability holds. The main purpose of this note is to emphasize that the approach of Saito and Mitsui makes it possible to quantify precisely the point where unconditional stability is lost in terms of the ratio of the drift (deterministic) and diffusion (stochastic) coefficients. This leads to a concept akin to deterministic A()-stability that may be useful in the stability analysis of more general methods. It is also shown that mean-square A-stability is recovered if the Theta Method parameter is increased beyond its normal range to the value 3/2.     

Zero and first-order phase shift correction for field map estimation with dual-echo GRE using bipolar gradients

A simple phase error correction technique used for field map estimation with a generally available dual-echo gradient-echo (GRE) sequence is presented. Magnetic field inhomogeneity maps estimated using two separate GRE volume acquisitions at different echo times are prone to dynamic motion errors between acquisitions. By using the dual-echo sequence, the data are collected during two back-to-back readout gradients in opposite polarity after a single radio frequency pulse, and interecho motion artifacts and alignment errors in field map estimation can be factored out. Residual phase error from the asymmetric readout pulses is modeled as an affine term in the readout direction. Results from phantom and human data suggest that the first-order phase correction term stays constant over time and, hence, can be applied to different data acquired with the same protocol over time. The zero-order phase correction term may change with time and is estimated empirically for different scans.     

Homogeneous time-resolved fluorescence assays for the detection of activity and inhibition of phosphatase enzymes employing phosphorescently labeled peptide substrates

A rapid, homogenous, antibody-free assay for phosphatase enzymes was developed using the phosphorescent platinum (II)-coproporphyrin label (PtCP) and time-resolved fluorescent detection. An internally quenched decameric peptide substrate containing a phospho-tyrosine residue, labeled with PtCP-maleimide and dabcyl-NHS at its termini was designed. Phosphatase catalysed dephosphorylation of the substrate resulted in a minor increase in PtCP signal, while subsequent cleavage by chymotrypsin at the dephosphorylated Tyr-Leu site provided a 3.5 fold enhancement of PtCP phosphorescence. This phosphorescence phosphatase enhancement assay was optimized to a 96 well plate format with detection on a commercial TR-F plate reader, and applied to measure the activity and inhibition of alkaline phosphatase, recombinant human CD45, and tyrosine phosphatases in Jurkat cell lysates within 40 min. Parameters of these enzymatic reactions such as K_m's, limits of detection (L.O.D's) and IC₅₀ values for the non-specific inhibitor sodium orthovanadate were also determined.     

Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: application to photodynamic tumour targeting

Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L(t), and depth at which the maximum width of the penetration pattern occurred, L(m), decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L(w), increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L(w) decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L(t) of 2.91 mm, L(m) of 2.14 mm, L(w) of 5.10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours.     

Compound Hub: efficiency gains through innovative sample management processes

While significant investments are made across the industry and increasingly also in academia to enhance or build a compound file, the efficient sourcing of compounds from in-house medical chemistry is frequently seen as a challenge. This article introduces the Compound Hub strategy developed at the Novartis Compound Archive. Central Compound Hubs in Basel and Cambridge were combined with web-based ordering of compounds and assays, providing assay-ready, solubilized samples to labs anywhere in the global research organization. Relieving scientists from time-intensive sample preparation tasks, error rates could be reduced through electronic processing and tracking of compounds/assays and the capture of medicinal chemistry compounds for the compound library could be increased by 75%.     

Construction of an Octanuclear Zn(Ⅱ)-Yb(Ⅲ)Schiff Base Complex for the NIR Luminescent Sensing of Nitrofuran Antibiotics

One near-infrared(NIR)luminescent octanuclear Zn(Ⅱ)-Yb(Ⅲ)complex[Zn6Yb2L4(OAc)2(DMF)EtOH](1)was obtained from a new mul-tidentate Schiff base Iigand.     

Transverse-mass dependence of two-pion correlations in Au+Au collisions at square root[s(NN)] = 130 GeV

Two-pion correlations in square root[s(NN)] = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to results from heavy-ion collisions at square root[s(NN)] = 4.1, 4.9, and 17.3 GeV, whereas the longitudinal radius increases monotonically with beam energy. The ratio of the outwards to sidewards transverse radii (R(out)/R(side)) is consistent with unity and independent of k(T).     

Pure drug nanoparticles in tablets: what are the dissolution limitations?

There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.