Interfacial Phenomena in Pharmaceutical Low Moisture Content Powder Processing

Powders are essential materials in the pharmaceutical industry, being involved in majority of all drug manufacturing. Powder flow and particle size are central particle properties addressed by means of particle engineering. The aim of the thesis was to gain knowledge on powder processing with restricted liquid addition, with a primary focus on particle coating and early granule growth. Furthermore, characterisation of this kind of processes was performed. A thin coating layer of hydroxypropyl methylcellulose was applied on individual particles of ibuprofen in a fluidised bed top-spray process. The polymeric coating improved the flow properties of the powder. The improvement was strongly related to relative humidity, which can be seen as an indicator of a change in surface hydrophilicity caused by the coating. The ibuprofen used in the present study had a d50 of 40 μm and thus belongs to the Geldart group C powders, which can be considered as challenging materials in top-spray coating processes. Ibuprofen was similarly coated using a novel ultrasound-assisted coating method. The results were in line with those obtained from powders coated in the fluidised bed process mentioned above. It was found that the ultrasound-assisted method was capable of coating single particles with a simple and robust setup. Granule growth in a fluidised bed process was inhibited by feeding the liquid in pulses. The results showed that the length of the pulsing cycles is of importance, and can be used to adjust granule growth. Moreover, pulsed liquid feed was found to be of greater significance to granule growth in high inlet air relative humidity. Liquid feed pulsing can thus be used as a tool in particle size targeting in fluidised bed processes and in compensating for changes in relative humidity of the inlet air. The nozzle function of a two-fluid external mixing pneumatic nozzle, typical for small scale pharmaceutical fluidised bed processes, was studied in situ in an ongoing fluidised bed process with particle tracking velocimetry. It was found that the liquid droplets undergo coalescence as they proceed away from the nozzle head. The coalescence was expected to increase droplet speed, which was confirmed in the study. The spray turbulence was studied, and the results showed turbulence caused by the event of atomisation and by the oppositely directed fluidising air. It was concluded that particle tracking velocimetry is a suitable tool for in situ spray characterisation. The light transmission through dense particulate systems was found to carry information on particle size and packing density as expected based on the theory of light scattering by solids. It was possible to differentiate binary blends consisting of components with differences in optical properties. Light transmission showed potential as a rapid, simple and inexpensive tool in characterisation of particulate systems giving information on changes in particle systems, which could be utilised in basic process diagnostics.

Investigating online reading with eye tracking and EEG : The influence of text format, reading task and parafoveal stimuli on reading processes

Research on reading has been successful in revealing how attention guides eye movements when people read single sentences or text paragraphs in simplified and strictly controlled experimental conditions. However, less is known about reading processes in more naturalistic and applied settings, such as reading Web pages. This thesis investigates online reading processes by recording participants eye movements. The thesis consists of four experimental studies that examine how location of stimuli presented outside the currently fixated region (Study I and III), text format (Study II), animation and abrupt onset of online advertisements (Study III), and phase of an online information search task (Study IV) affect written language processing. Furthermore, the studies investigate how the goal of the reading task affects attention allocation during reading by comparing reading for comprehension with free browsing, and by varying the difficulty of an information search task. The results show that text format affects the reading process, that is, vertical text (word/line) is read at a slower rate than a standard horizontal text, and the mean fixation durations are longer for vertical text than for horizontal text. Furthermore, animated online ads and abrupt ad onsets capture online readers attention and direct their gaze toward the ads, and distract the reading process. Compared to a reading-for-comprehension task, online ads are attended to more in a free browsing task. Moreover, in both tasks abrupt ad onsets result in rather immediate fixations toward the ads. This effect is enhanced when the ad is presented in the proximity of the text being read. In addition, the reading processes vary when Web users proceed in online information search tasks, for example when they are searching for a specific keyword, looking for an answer to a question, or trying to find a subjectively most interesting topic. A scanning type of behavior is typical at the beginning of the tasks, after which participants tend to switch to a more careful reading state before finishing the tasks in the states referred to as decision states. Furthermore, the results also provided evidence that left-to-right readers extract more parafoveal information to the right of the fixated word than to the left, suggesting that learning biases attentional orienting towards the reading direction.

Global, Local and Vector-Valued Tb Theorems on Non-Homogeneous Metric Spaces

Various Tb theorems play a key role in the modern harmonic analysis. They provide characterizations for the boundedness of Calderón-Zygmund type singular integral operators. The general philosophy is that to conclude the boundedness of an operator T on some function space, one needs only to test it on some suitable function b. The main object of this dissertation is to prove very general Tb theorems. The dissertation consists of four research articles and an introductory part. The framework is general with respect to the domain (a metric space), the measure (an upper doubling measure) and the range (a UMD Banach space). Moreover, the used testing conditions are weak. In the first article a (global) Tb theorem on non-homogeneous metric spaces is proved. One of the main technical components is the construction of a randomization procedure for the metric dyadic cubes. The difficulty lies in the fact that metric spaces do not, in general, have a translation group. Also, the measures considered are more general than in the existing literature. This generality is genuinely important for some applications, including the result of Volberg and Wick concerning the characterization of measures for which the analytic Besov-Sobolev space embeds continuously into the space of square integrable functions. In the second article a vector-valued extension of the main result of the first article is considered. This theorem is a new contribution to the vector-valued literature, since previously such general domains and measures were not allowed. The third article deals with local Tb theorems both in the homogeneous and non-homogeneous situations. A modified version of the general non-homogeneous proof technique of Nazarov, Treil and Volberg is extended to cover the case of upper doubling measures. This technique is also used in the homogeneous setting to prove local Tb theorems with weak testing conditions introduced by Auscher, Hofmann, Muscalu, Tao and Thiele. This gives a completely new and direct proof of such results utilizing the full force of non-homogeneous analysis. The final article has to do with sharp weighted theory for maximal truncations of Calderón-Zygmund operators. This includes a reduction to certain Sawyer-type testing conditions, which are in the spirit of Tb theorems and thus of the dissertation. The article extends the sharp bounds previously known only for untruncated operators, and also proves sharp weak type results, which are new even for untruncated operators. New techniques are introduced to overcome the difficulties introduced by the non-linearity of maximal truncations.

A maximal operator, Carleson's embedding, and tent spaces for vector-valued functions

This thesis is concerned with the area of vector-valued Harmonic Analysis, where the central theme is to determine how results from classical Harmonic Analysis generalize to functions with values in an infinite dimensional Banach space. The work consists of three articles and an introduction. The first article studies the Rademacher maximal function that was originally defined by T. Hytönen, A. McIntosh and P. Portal in 2008 in order to prove a vector-valued version of Carleson's embedding theorem. The boundedness of the corresponding maximal operator on Lebesgue-(Bochner) -spaces defines the RMF-property of the range space. It is shown that the RMF-property is equivalent to a weak type inequality, which does not depend for instance on the integrability exponent, hence providing more flexibility for the RMF-property. The second article, which is written in collaboration with T. Hytönen, studies a vector-valued Carleson's embedding theorem with respect to filtrations. An earlier proof of the dyadic version assumed that the range space satisfies a certain geometric type condition, which this article shows to be also necessary. The third article deals with a vector-valued generalizations of tent spaces, originally defined by R. R. Coifman, Y. Meyer and E. M. Stein in the 80's, and concerns especially the ones related to square functions. A natural assumption on the range space is then the UMD-property. The main result is an atomic decomposition for tent spaces with integrability exponent one. In order to suit the stochastic integrals appearing in the vector-valued formulation, the proof is based on a geometric lemma for cones and differs essentially from the classical proof. Vector-valued tent spaces have also found applications in functional calculi for bisectorial operators. In the introduction these three themes come together when studying paraproduct operators for vector-valued functions. The Rademacher maximal function and Carleson's embedding theorem were applied already by Hytönen, McIntosh and Portal in order to prove boundedness for the dyadic paraproduct operator on Lebesgue-Bochner -spaces assuming that the range space satisfies both UMD- and RMF-properties. Whether UMD implies RMF is thus an interesting question. Tent spaces, on the other hand, provide a method to study continuous time paraproduct operators, although the RMF-property is not yet understood in the framework of tent spaces.

Elliptic flow of thermal photons in heavy-ion collisions at Relativistic Heavy Ion Collider and Large Hadron Collider

We calculate the thermal photon transverse momentum spectra and elliptic flow in $\sqrt{s_{NN}} = 200$ GeV Au+Au collisions at RHIC and in $\sqrt{s_{NN}} = 2.76$ TeV Pb+Pb collisions at the LHC, using an ideal-hydrodynamical framework which is constrained by the measured hadron spectra at RHIC and LHC. The sensitivity of the results to the QCD-matter equation of state and to the photon emission rates is studied, and the photon $v_2$ is discussed in the light of the photonic $p_T$ spectrum measured by the PHENIX Collaboration. In particular, we make a prediction for the thermal photon $p_T$ spectra and elliptic flow for the current LHC Pb+Pb collisions.

The decline of malaria in Finland – the impact of the vector and social variables

Background: Malaria was prevalent in Finland in the 18th century. It declined slowly without deliberate counter-measures and the last indigenous case was reported in 1954. In the present analysis of indigenous malaria in Finland, an effort was made to construct a data set on annual malaria cases of maximum temporal length to be able to evaluate the significance of different factors assumed to affect malaria trends. Methods: To analyse the long-term trend malaria statistics were collected from 1750–2008. During that time, malaria frequency decreased from about 20,000 – 50,000 per 1,000,000 people to less than 1 per 1,000,000 people. To assess the cause of the decline, a correlation analysis was performed between malaria frequency per million people and temperature data, animal husbandry, consolidation of land by redistribution and household size. Results: Anopheles messeae and Anopheles beklemishevi exist only as larvae in June and most of July. The females seek an overwintering place in August. Those that overwinter together with humans may act as vectors. They have to stay in their overwintering place from September to May because of the cold climate. The temperatures between June and July determine the number of malaria cases during the following transmission season. This did not, however, have an impact on the longterm trend of malaria. The change in animal husbandry and reclamation of wetlands may also be excluded as a possible cause for the decline of malaria. The long-term social changes, such as land consolidation and decreasing household size, showed a strong correlation with the decline of Plasmodium. Conclusion: The indigenous malaria in Finland faded out evenly in the whole country during 200 years with limited or no counter-measures or medication. It appears that malaria in Finland was basically a social disease and that malaria trends were strongly linked to changes in human behaviour. Decreasing household size caused fewer interactions between families and accordingly decreasing recolonization possibilities for Plasmodium. The permanent drop of the household size was the precondition for a permanent eradication of malaria.