Particle trapping and banding in rapid solidification

Solidification of suspensions of small particles, from nanometer to colloidal (sub-micrometer) sizes, produces biomimetic materials with novel microstructure and expanding applications in microfluidics, nanotechnology and tissue engineering. To facilitate understanding and control of the solidification process, a thermodynamically consistent theory is here developed. We use the Boltzmann particle velocity distribution to determine the probability a particle is engulfed by an advancing solid-liquid interface and obtain the resulting kinetic phase diagram. We demonstrate use of the theory by predicting the formation of bands in rapidly solidified alumina suspensions, in quantitative agreement with experiment

Aphidophagous Coccinellids in Alfalfa, Small Grains, and Maize in Eastern South Dakota

In a 13-year study of aphidophagous coccinellids associated with alfalfa (Medicago sativa), maize (Zea mays), and small grain crops in eastern South Dakota, the following species were consistently associated with the crops: Hippodamia convergens, H. tredecimpunctata tibialis, H. parenthesis, Coleomegilla maculata lengi, Coccinella transversoguttata richardsoni, Cycloneda munda, and Adalia bipunctata. All species except A. bipunctata were associated with each of the three crops, while A. bipunctata occurred only in maize. Relative abundances of each species varied among crops and among years. Although only seven species were associated with the crops, additional species were captured on sticky traps stationed adjacent to sampled fields. The species diversity of immature coccinellids did not differ among crops but did differ among years. The diversity of adults differed among crops and years. The site from which samples were taken had no influence on the diversity of immatures or adults. Species relative abundances in alfalfa and small grains were more similar to each other than they were to relative abundances in maize

Atmospheric effects on remote sensing of non-uniform temperature sources

The equations of transfer, for a plane-parallel scattering atmosphere with a point source of energy on the lower bounding surface, were solved for various values of sensor/point source orientation and optical depths. Applications of this analysis to Skylab and ERTS mission are discussed, and requirements for atmospheric property data and radiation transfer properties are considered

Manometric Temperature Measurement (MTM) lyophilisation of a challenging clinical trial pharmaceutical

INTRODUCTION Cancer Research UK Formulation Unit The Formulation Unit based at the University of Strathclyde in Glasgow has a research and development history in excess of 25 years, being funded by, and working in partnership with, firstly Cancer Research Campaign, and since 2002, with Cancer Research UK. The Unit is based in an entirely academic University setting, and since 2004 has been licensed by the UK government Medicines and Healthcare products Regulatory Agency (MHRA) for research, development and manufacture of Phase I/II novel small molecule cancer therapeutics and diagnostics. Research programs have delivered new formulations to clinical trial as either sterile or non-sterile presentations. However, the Unit’s specialty is based around small volume parenteral product manufacture. Boronophenylalanine (L-BPA) in Boron Neutron Capture Therapy (BNCT) L-BPA is the premier pharmaceutical selection in BNCT in treatment of selected head and neck tumours. BNCT relies on localisation of boron 10 within a tumour mass, made possible by the amino acid carrier portion of the L-BPA molecule. Phenylalanine is selectively transported across the blood brain barrier and then into astrocytic cells by a LAT-1 transporter system that is up-regulated in tumour. A targeted external neutron beam activates the accumulated L-BPA. In brief, neutron capture by boron causes nuclear re-arrangement and formation of a high linear energy transfer alpha particle and lithium 7 nuclei. Thus the patient is dosed with localised radiotherapy. OLD FORMULATION Issues existed with the previous standard formulation of L-BPA in fructose. L-BPA complexed with fructose has low solubility of around 30mg/mL. Consequently, large administration volumes are required to achieve clinical dosing in tens of grams of drug per patient. Moreover, L-BPA in fructose solutions must be freshly prepared and administered within 48 hours for reasons of product instability (Henriksson et al, 2008). Although rare, hereditary fructose intolerance needs to be considered. Taken together, L-BPA production, preparation and patient dosing is highly challenging. NEW FORMULATION Restrictions The Formulation Unit developed a new improved formulation; the drug product was a lyophilized pH8 solution of L-BPA at 100mg/mL in 110mg/mL mannitol (Schmidt et al, 2011). When lyophilised, a shelf life of 48 months was supported for the drug product. Whilst a three times increase in solubility, and a significantly enhanced product lifetime were worthy formulation enhancements, a new restriction emerged; the solution for lyophilisation contained 21% w/v solids far exceeding the ‘normal’ region of 2% w/v to 5% w/v (Boylan and Nail, 2009). Moreover, the lyophilisation cycle of 6 days was considered commercially unfavourable. A shortened drying cycle of 1 to 3 days would be preferred. Research was therefore initiated to reduce drying cycle time utilising Manometric Temperature Measurement (MTM) technology. MTM Studies MTM controlled freeze drying systems were originally marketed in the first decade of the new millennium. The ability to use software to calculate the performance at the freeze-drying front in real time is scientifically and commercially appealing. The possibility to optimize processing conditions at that same time as data is being received invites the prospect of a reduced experimentation phase thereby rapidly reaching the goal of a maximally efficient freeze drying cycle. In theory, even a minimally experienced operator could achieve this outcome. In summary, MTM functions by taking pressure rise information at regular intervals (Giesler et al, 2007). Based on SMART® software (SP Scientific, Stone Ridge, NY, USA), hourly pressure rise data are taken at a rate of 10 samples per second. The system calculates the product temperature at the sublimation interface and mass transfer resistance of the product. Adjustments are then automatically made to the shelf temperature and system pressure to achieve a calculated target product temperature. The end of primary drying can be determined by comparing the vapour pressure of ice with the system chamber pressure. Input data is minimal, such as vial number, inner vial area, fill volume and weight, concentration, product critical temperature. MATERIALS AND METHODS Chemicals Syntagon AB, Södertälje, Sweden manufactured BPA raw material according to EU current Good Manufacturing Practice (cGMP). D-mannitol (Ph. Eur) was sourced from Sigma-Aldrich, Poole, UK, and fuming hydrochloric acid and sodium hydroxide pellets (both extra pure Ph. Eur., BP, JP, NF) were obtained from VWR International, Lutterworth, UK. Water for Irrigation (WFI) in bulk was acquired from Baxter’s Healthcare Ltd., Norfolk, UK. Type 1 clear glass 50mL vials with 20mm butyl rubber stoppers (proved clean), crimped with 20mm tear off aluminium overseals were all from Adelphi Healthcare Packaging, Haywards Heath, UK. Lyophilisation equipment MTM software (SMART®) was operated on an FTS Systems Lyostar II drier (Biopharma, Winchester, UK). CONCLUSION A new improved L-BPA formulation in mannitol has been developed and used in human clinical trial. Further research using MTM technology succeeded in reducing a 6 day drug product drying cycle to 53 hours. The formulation exhibited non-ideal behaviour, and MTM failed to predict drying parameters, e.g., base of vial temperature, that are more closely replicated in ‘ideal’ test articles such as a 5% mannitol comparator. Further test lyophilisations are required to reach ideal. ACKNOWLEDGMENTS This research is funded by Cancer Research UK. REFERENCES 1. Boylan, J.C. and Nail, S.L. Parenteral Products, in: Florence, A.T. and Siepman, J. (Eds.), Modern Pharmaceutics. Informa Healthcare, New York, 565-609 (2009). 2. Giesler, H.; Kramer, T. and Pikal, M. J. Use of manometric temperature measurement (MTM) and SMART freeze dryer technology for development of an optimised freeze drying cycle. J. Pharm Sci. 96(12), 3402-3418 (2007). 3. Henriksson, R.; Capala, J.; Michanek, A.; Lindahl, S.A.; Satford, L.G.; Franzen, L.; Blomquist, E.; Westlin, J.E. and Bergenheim, A.T. Boron neutron capture therapy (BNCT) for glioblastoma multiforme: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA). Radiotherapy and Oncology 88, 183-191 (2008). 4. Schmidt, E.; Dooley, N.; Ford, S. J.; Elliott, M. and Halbert, G. W. Physicochemical investigation of the influence of saccharide based parenteral formulation excipients on L-p-boronphenylalanine solubilisation for Boron Neutron Capture Therapy. J. Pharm. Sci. 101(1), 223-232 (2011)

Information entropy in fragmenting systems

The possibility of facing critical phenomena in nuclear fragmentation is a topic of great interest. Different observables have been proposed to identify such a behavior, in particular, some related to the use of information entropy as a possible signal of critical behavior. In this work we critically examine some of the most widespread used ones comparing its performance in bond percolation and in the analysis of fragmenting Lennard Jones Drops.Comment: 3 pages, 3 figure

Market segmentation through information

An information designer has precise information about consumers' preferences over products sold by oligopolists. The designer chooses what information to reveal to differentiated firms who, then, compete on price by making personalized offers. We ask what market outcomes the designer can achieve. The information designer is a metaphor for an internet platform who collects data about users and sells it to firms who can, in turn, target discounts and promotions towards different consumers. Our analysis provides new benchmarks demonstrating the power that users' data can endow internet platforms with. These benchmarks speak directly to current regulatory debates

Bound states in weakly disordered spin ladders

We study the appearance of bound states in the spin gap of spin-1/2 ladders induced by weak bond disorder. Starting from the strong-coupling limit, i.e., the limit of weakly coupled dimers, we perform a projection on the single-triplet subspace and derive the position of bound states for the single impurity problem of one modified coupling as well as for small impurity clusters. The case of a finite concentration of impurities is treated with the coherent-potential approximation in the strong-coupling limit and compared with numerical results. Furthermore, we analyze the details in the structure of the density of states and relate their origin to the influence of impurity clusters.Comment: 2 pages, 1 figure. Proceedings of SCES'04, to appear in Physica

Bubbles and Filaments: Stirring a Cahn-Hilliard Fluid

The advective Cahn-Hilliard equation describes the competing processes of stirring and separation in a two-phase fluid. Intuition suggests that bubbles will form on a certain scale, and previous studies of Cahn-Hilliard dynamics seem to suggest the presence of one dominant length scale. However, the Cahn-Hilliard phase-separation mechanism contains a hyperdiffusion term and we show that, by stirring the mixture at a sufficiently large amplitude, we excite the diffusion and overwhelm the segregation to create a homogeneous liquid. At intermediate amplitudes we see regions of bubbles coexisting with regions of hyperdiffusive filaments. Thus, the problem possesses two dominant length scales, associated with the bubbles and filaments. For simplicity, we use use a chaotic flow that mimics turbulent stirring at large Prandtl number. We compare our results with the case of variable mobility, in which growth of bubble size is dominated by interfacial rather than bulk effects, and find qualitatively similar results.Comment: 20 pages, 27 figures. RevTeX

Twisted k-graph algebras associated to Bratteli diagrams

Given a system of coverings of k-graphs, we show that the cohomology of the resulting (k+1)-graph is isomorphic to that of any one of the k-graphs in the system. We then consider Bratteli diagrams of 2-graphs whose twisted C*-algebras are matrix algebras over noncommutative tori. For such systems we calculate the ordered K-theory and the gauge-invariant semifinite traces of the resulting 3-graph C*-algebras. We deduce that every simple C*-algebra of this form is Morita equivalent to the C*-algebra of a rank-2 Bratteli diagram in the sense of Pask-Raeburn-R{\o}rdam-Sims.Comment: 28 pages, pictures prepared using tik