Experiences in batch trajectory alignment for pharmaceutical process improvement through multivariate latent variable modelling

The primary objective of batch data as trajectory alignment (or synchronization) is to standardize the data sampling per batch according to the evolution of the process, and secondarily to homogenize the samples per run. The use of an indicator variable performs both objectives well. Two examples from the pharmaceutical sector are discussed to illustrate the different ways to deal with uneven samples across batches and across variables in the same batch. Since trajectory alignment requires large time investment, a simple triage approach is proposed to assess the need to analyze the dynamics of a given process and hence perform alignment. The presented examples are representative of a broad variety of batch processes that are operated by recipe in the pharmaceutical sector. In our experience, the variables associated with the automation triggers in these recipes are the best indicator variables to use for alignment. This is due to (i) the fact that the trigger variables are easy to identify from the automation of the recipe, (ii) operators are familiar with these, (iii) the target values for triggers are known a priori and hence the resulting alignment scheme can be performed in real-time for monitoring applications and (iv) it makes the monitoring scheme easy to understand and justify around the design-space since the design-space may originally be defined in terms of the trigger variables for each phase of the batch.     

Nonlinear mappings in problem solving and their PSO-based development

The study is devoted to a concept and algorithmic realization of nonlinear mappings aimed at increasing the effectiveness of the problem solving method. Given the original input space X and a certain problem solving method M, designed is a nonlinear mapping ? so that the method operating in the transformed space M(?(X)) becomes more efficient. The nonlinear mappings realize a transformation of X through contractions and expansions of selected regions of the original space. In particular, we show how a piecewise linear mapping is optimized by using particle swarm optimization (PSO) and a suitable fitness function quantifying the objective of the problem. Several families of problems are investigated and illustrated through illustrative experimental results.     

Direct and transmission milling of suspended silicon nitride membranes with a focused helium ion beam

Helium ion milling of suspended silicon nitride thin films is explored. Milled squares patterned by scanning helium ion microscope are subsequently investigated by atomic force microscopy and the relation between ion dose and milling depth is measured for both the direct (side of ion incidence) and transmission (side opposite to ion incidence) regimes. We find that direct-milling depth varies linearly with beam dose while transmission-milling depth varies with the square of the beam dose, resulting in a straightforward method of controlling local film thickness.     

Electrostatic self-assembly of macroscopic crystals using contact electrification

Self-assembly of components larger than molecules into ordered arrays is an efficient way of preparing microstructured materials with interesting mechanical and optical properties. Although crystallization of identical particles or particles of different sizes or shapes can be readily achieved, the repertoire of methods to assemble binary lattices of particles of the same sizes but with different properties is very limited. This paper describes electrostatic self-assembly of two types of macroscopic components of identical dimensions using interactions that are generated by contact electrification. The systems we have examined comprise two kinds of objects (usually spheres) made of different polymeric materials that charge with opposite electrical polarities when agitated on flat, metallic surfaces. The interplay of repulsive interactions between like-charged objects and attractive interactions between unlike-charged ones results in the self-assembly of these objects into highly ordered, closed arrays. Remarkably, some of the assemblies that form are not electroneutral-that is, they possess a net charge. We suggest that the stability of these unusual structures can be explained by accounting for the interactions between electric dipoles that the particles in the aggregates induce in their neighbours.     

Activation cross sections of proton induced nuclear reactions on natural hafnium

In a systematic study of light charged particle induced nuclear reactions we investigated the excitation functions of proton induced reactions on natural hafnium targets. Experimental excitation functions of proton induced reactions up to 36 MeV on high purity natural hafnium were determined using the stacked foil activation technique. High resolution off-line gamma-ray spectrometry was applied to assess the activity of each foil. From the measured activity independent and/or cumulative elemental or isotopic cross section data for production of Ta, Hf and Lu radioisotopes were determined. The experimental data were compared to the data published earlier by other authors and to results of TALYS theoretical code taken from TENDL-2010 database. Thick target yields of the investigated radionuclides were calculated from the excitation function that was deduced as an analytical fit to our experimental cross section data points.     

The Structure and Bond Strength of Composite Carbide Coatings (WC-Co + Ni) Deposited on Ductile Cast Iron by Thermal Spraying

An investigation was conducted to determine the role of Ni particles in the WC-Co coating produced with the supersonic method on microstructure, mechanical, and wear properties in a system of type: WC-Co coating/ductile cast iron. The microstructure of the thermal-sprayed WC-Co + Ni coating was characterized by scanning electron and transmission electron microscopes as well as the analysis of chemical and phase composition in microareas (EDS, XRD). The microstructure of the WC-Co + Ni coating consisted of large, partially molten Ni particles and very fine grains of WC embedded in cobalt matrix, coming to the size of nanocrystalline. Moreover, the results were discussed in reference to examination of bending strength considering cracking and delamination in the system of (WC-Co + Ni)/ductile cast iron as well as hardness and wear resistance of the coating. It was found that the addition of Ni particles was significantly increase resistance to cracking and wear behavior in the studied system.     

Evidence for genetic influence on both cross-situation and situation-specific components of behavior.

An assumption often made in the study of personality and in social psychology is that methods variance and situation-specific effects, as key components of measured behavioral variance, are environmental effects. The results of the present research refute that assumption. Nine measures—3 aspects of temperament measured in each of 3 ways—were obtained at age 24 months for twin sibships participating in the Louisville Twin Study. This report describes a new model that captures the unique information potentially available in such data, by combining multitrait–multimethod and twin–family analytic designs. The results indicated significant genetic influence on methods–situations components of variance along with genetic influence on traits. The findings support heuristics that include both situation-specific patterns of behavior and cross-situational consistencies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thermodynamics of the Superconducting State in Calcium at 200 GPa

The thermodynamic parameters of the superconducting state in Calcium under the pressure at 200 GPa were calculated. The Coulomb pseudopotential values (μ ^⋆) from 0.1 to 0.3 were taken into consideration. It has been shown that the specific heat’s jump at the critical temperature and the thermodynamic critical field near zero Kelvin strongly decrease with μ ^⋆. The dimensionless ratios r ₁≡ΔC(T _C)/C ^N (T _C) and r₂ o T_CC^N(T_C)/H²_C(0)r_{2}\equiv T_{\mathrm{C}}C^{N}(T_{\mathrm{C}})/H^{2}_{\mathrm{C}}(0) significantly differ from the predictions based on the BCS model. In particular, r ₁ decreases from 2.64 to 1.97 with the Coulomb pseudopotential; whereas r ₂ increases from 0.140 to 0.157. The numerical results have been supplemented by the analytical approach.     

Photothermal optical coherence tomography of epidermal growth factor receptor in live cells using immunotargeted gold nanospheres

Molecular imaging is a powerful tool for investigating disease processes and potential therapies in both in vivo and in vitro systems. However, high resolution molecular imaging has been limited to relatively shallow penetration depths that can be accessed with microscopy. Optical coherence tomography (OCT) is an optical analogue to ultrasound with relatively good penetration depth (1-2 mm) and resolution (approximately 1-10 microm). We have developed and characterized photothermal OCT as a molecular contrast mechanism that allows for high resolution molecular imaging at deeper penetration depths than microscopy. Our photothermal system consists of an amplitude-modulated heating beam that spatially overlaps with the focused spot of the sample arm of a spectral-domain OCT microscope. Validation experiments in tissuelike phantoms containing gold nanospheres that absorb at 532 nm revealed a sensitivity of 14 ppm nanospheres (weight/weight) in a tissuelike environment. The nanospheres were then conjugated to anti-EGFR, and molecular targeting was confirmed in cells that overexpress EGFR (MDA-MB-468) and cells that express low levels of EGFR (MDA-MB-435). Molecular imaging in three-dimensional tissue constructs was confirmed with a significantly lower photothermal signal (p<0.0001) from the constructs composed of cells that express low levels of EGFR compared to the overexpressing cell constructs (300% signal increase). This technique could potentially augment confocal and multiphoton microscopy as a method for deep-tissue, depth-resolved molecular imaging with relatively high resolution and target sensitivity, without photobleaching or cytotoxicity.