Accurate mass-based analysis in human sport doping control : Application of liquid chromatography - time-of-flight mass spectrometry

Human sport doping control analysis is a complex and challenging task for anti-doping laboratories. The List of Prohibited Substances and Methods, updated annually by World Anti-Doping Agency (WADA), consists of hundreds of chemically and pharmacologically different low and high molecular weight compounds. This poses a considerable challenge for laboratories to analyze for them all in a limited amount of time from a limited sample aliquot. The continuous expansion of the Prohibited List obliges laboratories to keep their analytical methods updated and to research new available methodologies. In this thesis, an accurate mass-based analysis employing liquid chromatography - time-of-flight mass spectrometry (LC-TOFMS) was developed and validated to improve the power of doping control analysis. New analytical methods were developed utilizing the high mass accuracy and high information content obtained by TOFMS to generate comprehensive and generic screening procedures. The suitability of LC-TOFMS for comprehensive screening was demonstrated for the first time in the field with mass accuracies better than 1 mDa. Further attention was given to generic sample preparation, an essential part of screening analysis, to rationalize the whole work flow and minimize the need for several separate sample preparation methods. Utilizing both positive and negative ionization allowed the detection of almost 200 prohibited substances. Automatic data processing produced a Microsoft Excel based report highlighting the entries fulfilling the criteria of the reverse data base search (retention time (RT), mass accuracy, isotope match). The quantitative performance of LC-TOFMS was demonstrated with morphine, codeine and their intact glucuronide conjugates. After a straightforward sample preparation the compounds were analyzed directly without the need for hydrolysis, solvent transfer, evaporation or reconstitution. The hydrophilic interaction technique (HILIC) provided good chromatographic separation, which was critical for the morphine glucuronide isomers. A wide linear range (50-5000 ng/ml) with good precision (RSD<10%) and accuracy (±10%) was obtained, showing comparable or better performance to other methods used. In-source collision-induced dissociation (ISCID) allowed confirmation analysis with three diagnostic ions with a median mass accuracy of 1.08 mDa and repeatable ion ratios fulfilling WADA s identification criteria. The suitability of LC-TOFMS for screening of high molecular weight doping agents was demonstrated with plasma volume expanders (PVE), namely dextran and hydroxyethylstarch (HES). Specificity of the assay was improved, since interfering matrix compounds were removed by size exclusion chromatography (SEC). ISCID produced three characteristic ions with an excellent mean mass accuracy of 0.82 mDa at physiological concentration levels. In summary, by combining TOFMS with a proper sample preparation and chromatographic separation, the technique can be utilized extensively in doping control laboratories for comprehensive screening of chemically different low and high molecular weight compounds, for quantification of threshold substances and even for confirmation. LC-TOFMS rationalized the work flow in doping control laboratories by simplifying the screening scheme, expediting reporting and minimizing the analysis costs. Therefore LC-TOFMS can be exploited widely in doping control, and the need for several separate analysis techniques is reduced.

Room-temperature synthesis of gold nanoparticles - Size-control by slow addition

We report a simple and rapid process for the room-temperature synthesis of gold nanoparticles using tannic acid, a green reagent, as both the reducing and stabilising agent. We systematically investigated the effect of pH on the size distribution of nanoparticles synthesized. Based on induction time and zeta- potential measurements, we show that particle size distribution is controlled by a fine balance between the rates of reduction (determined by the initial pH of reactants) and coalescence (determined by the pH of the reaction mixture) in the initial period of growth. This insight led to the optimal batch process for size-controlled synthesis of 2-10 nm gold nanoparticles - slow addition (within 10 minutes) of chloroauric acid into tannic acid.

“And now to the rest of the trash…” Representations of begging Roma and an ideal society in two Nordic newspapers

Since begging East European Roma became a common view in the streets of larger Nordic cities, vivid discussions about their presence and activities have been carried out in the mass media. This thesis examines the public debates in Finland and Norway through a discursive analysis and comparison of press content from the two countries. The aim of the study is firstly to identify the prominent discourses which construct certain images of the beggars, as well as the elements and internal logics that these discourses are constructed around. But in addition to scrutinizing representations of the Roma, also an opposite perspective is applied. In accordance with the theoretical concept of ‘othering’, debates about ‘them’ are assumed to simultaneously reveal something significant about ‘us’. The second research question is thus what kind of images of the ideal Finnish and Norwegian societies are reflected in the data, and which societal values are salient in these images. The analysis comprises 79 texts printed in the main Finnish and Norwegian quality newspapers; Helsingin Sanomat and Aftenposten. The data consists of news articles, editorials, columns and letters to the editor from a three-month period in the summer of 2010. The analysis was carried out within the theoretical and methodological framework of critical discourse analysis as outlined by Norman Fairclough. A customized nine-step coding scheme was developed in order to reach the most central dimensions of the texts. Seven main discourses were identified; the Deprivation-solidarity, Human rights, Order, Crime, Space and majority reactions, Authority control, and Authority critique discourse. These were grouped into two competing normative stances on what an ideal society looks like; the exclusionary and the inclusionary stance. While the exclusionary stance places the begging Roma within a frame of crime, illegitimate use of public space and threat to the social order, the other advocates an attitude of solidarity and humanitarian values. The analysis points to a dominance of the former, although it is challenged by the latter. The Roma are “individualized” by quoting and/or presenting them by name in a fair part of the Finnish news articles. In Norway, the opposite is true; there the beggars are dominantly presented as anonymous and passive. Overall, the begging Roma are subjected to a double bind as they are faced with simultaneous expectations of activity and passivity. Theories relating to moral panics and ‘the good enemy’ provide for a deepened understanding of the intensity of the debates. Keywords: East European Roma, begging, media, newspapers, Helsingin Sanomat, Aftenposten, critical discourse analysis, Norman Fairclough, othering, ideal society, moral panics, good enemy, double bind, Finland, Norway

Ball wear and its control in the grinding of a lead-zinc sulphide ore

Marked ball grinding tests were carried out in the laboratory with a lead-zinc sulphide ore under different experimental conditions using high carbon low alloy steel (cast and forged) and high chrome cast iron balls. Relative ball wear as a function of grinding period and milling conditions was evaluated for the different types of ball materials. The role of corrosion and abrasion-erosion in the wear of grinding media is brought out. Methods to minimise ball wear through control of mill atmosphere and addition of reagents are discussed.

Nutritional evaluation of silage made from the toxic weed parthenium hysterophorus in animals

After ensilation, the toxic Compositae weed Parthenium hysterophorus was devoid of the toxic principle parthenin. Laboratory-scale ensilation indicated that no parthenin was detectable after 5 wk of anaerobic fermentation. For animal feeding studies, silage was made on a large scale from Parthenium mixed with maize or from Parthenium alone. Crossbred bull and buffalo bull calves were fed diets containing the silages, or control diet without silage, for 12 wk. The animals consumed both silages with relish, and body weight gains of silage-fed calves did not differ from those of the controls. The digestibilities of dry matter, fibre and nitrogen-free extract were greater with the control diet, but the biological value of proteins tended to be greater with the silage-containing diets. Haematological studies indicated no significant differences between experimental and control groups in selected parameters, except for a reduction in blood urea nitrogen in the animals fed silage. The possible causes for these biochemical alterations are discussed. Since the nutritive value of Parthenium silage compares favourably with the standard diet, and Parthenium seeds collected from the silage did not germinate, we suggest that ensilation can be used as an additional method in the containment and eradication of these plants, which grow wild in India.

Ball wear mechanisms and control in the grinding of sulfide and phosphate ores

Marked ball grinding tests were carried out in the laboratory using high carbon low alloy steel (cast and forged) and high chrome cast iron balls. Relative ball wear as a function of grinding period and milling conditions was evaluated for the different type of ball materials in the grinding of lead-zinc sulphide and phosphate ores. Results indicated that ball wear increased with time and showed a sharp increase for wet grinding over dry grinding. Ball wear under wet grinding conditions was also influenced by the gaseous atmosphere in the mill. The influence of oxygen on the corrosive wear of grinding balls was increasingly felt in case of sulphide ore grinding. The grinding ball materials could be arranged in the following order with respect to their overall wear resistance:

Secretion of endocrine signals by the primate embryo during the peri-implantation period

Development of preimplantation embryos and blastocyst implantation are critical early events in the establishment of pregnancy. In primates, embryonic signals, secreted during the peri-implantation period, are believed to play a major role in the regulation of embryonic differentiation and implantation. However, only limited progress has been made in the molecular and functional characterization of embryonic signals, partly due to severe paucity of primate embryos and the lack of optimal culture conditions to obtain viable embryo development. Two embryonic (endocrine) secretions, i.e. chorionic gonadotrophin (CG) and gonadotrophin releasing hormone (GnRH) are being studied. This article reviews the current status of knowledge on the recovery and culture of embryos, their secretion of CG, GnRH and other potential endocrine signals and their regulation and physiological role(s) during the peri-implantation period in primates, including humans.

Driven Heisenberg magnets: Nonequilibrium criticality, spatiotemporal chaos and control

We drive a d-dimensional Heisenberg magnet using an anisotropic current. The continuum Langevin equation is analysed using a dynamical renormalization group and numerical simulations. We discover a rich steady-state phase diagram, including a critical point in a new nonequilibrium universality class, and a spatiotemporally chaotic phase. The latter may be controlled in a robust manner to target spatially periodic steady states with helical order.

Robustness Study of a Dynamic Inversion Control Law for a High Performance Aircraft

In the design of °ight control system modeling uncertainties in the form of param-eter variations is one of the major problems. It is even more critical for high performance aircrafts,since such aircrafts are purposefully designed unstable to enhance their performance (especially ma-neuverability). Hence the °ight control system needs to be quite e®ective in both assuring accurate tracking of pilot commands, while simultaneously assuring overall stability of the aircraft. In addi-tion, the control system must also be su±ciently robust to cater for possible parameter variations and inaccuracies . The primary aim of this paper is to carry out a robustness study of a dynamic inversion based nonlinear control design for a high performance aircraft, which has been developed recently [1].

An instantaneous control model for flow control in an ATM network

This paper is concerned with the optimal flow control of an ATM switching element in a broadband-integrated services digital network. We model the switching element as a stochastic fluid flow system with a finite buffer, a constant output rate server, and a Gaussian process to characterize the input, which is a heterogeneous set of traffic sources. The fluid level should be maintained between two levels namely b1 and b2 with b1critical levels. Also the application of instantaneous control on the ATM network is considered

Quenching across quantum critical points in periodic systems: Dependence of scaling laws on periodicity

We study the quenching dynamics of a many-body system in one dimension described by a Hamiltonian that has spatial periodicity. Specifically, we consider a spin-1/2 chain with equal xx and yy couplings and subject to a periodically varying magnetic field in the (z) over cap direction or, equivalently, a tight-binding model of spinless fermions with a periodic local chemical potential, having period 2q, where q is a positive integer. For a linear quench of the strength of the magnetic field (or chemical potential) at a rate 1/tau across a quantum critical point, we find that the density of defects thereby produced scales as 1/tau(q/(q+1)), deviating from the 1/root tau scaling that is ubiquitous in a range of systems. We analyze this behavior by mapping the low-energy physics of the system to a set of fermionic two-level systems labeled by the lattice momentum k undergoing a nonlinear quench as well as by performing numerical simulations. We also show that if the magnetic field is a superposition of different periods, the power law depends only on the smallest period for very large values of tau, although it may exhibit a crossover at intermediate values of tau. Finally, for the case where a zz coupling is also present in the spin chain, or equivalently, where interactions are present in the fermionic system, we argue that the power associated with the scaling law depends on a combination of q and the interaction strength.

An Accurate Fractional Period Delay Generation System

An all-digital technique is proposed for generating an accurate delay irrespective of the inaccuracies of a controllable delay line. A subsampling technique-based delay measurement unit (DMU) capable of measuring delays accurately for the full period range is used as the feedback element to build accurate fractional period delays based on input digital control bits. The proposed delay generation system periodically measures and corrects the error and maintains it at the minimum value without requiring any special calibration phase. Up to 40x improvement in accuracy is demonstrated for a commercial programmable delay generator chip. The time-precision trade-off feature of the DMU is utilized to reduce the locking time. Loop dynamics are adjusted to stabilize the delay after the minimum error is achieved, thus avoiding additional jitter. Measurement results from a high-end oscilloscope also validate the effectiveness of the proposed system in improving accuracy.

INST: An Integrated Steering Framework for Critical Weather Applications

Online remote visualization and steering of critical weather applications like cyclone tracking are essential for effective and timely analysis by geographically distributed climate science community. A steering framework for controlling the high-performance simulations of critical weather events needs to take into account both the steering inputs of the scientists and the criticality needs of the application including minimum progress rate of simulations and continuous visualization of significant events. In this work, we have developed an integrated user-driven and automated steering framework INST for simulations, online remote visualization, and analysis for critical weather applications. INST provides the user control over various application parameters including region of interest, resolution of simulation, and frequency of data for visualization. Unlike existing efforts, our framework considers both the steering inputs and the criticality of the application, namely, the minimum progress rate needed for the application, and various resource constraints including storage space and network bandwidth to decide the best possible parameter values for simulations and visualization.

Synchronization of globally coupled two-state stochastic oscillators with a state-dependent refractory period

We present a model of identical coupled two-state stochastic units, each of which in isolation is governed by a fixed refractory period. The nonlinear coupling between units directly affects the refractory period, which now depends on the global state of the system and can therefore itself become time dependent. At weak coupling the array settles into a quiescent stationary state. Increasing coupling strength leads to a saddle node bifurcation, beyond which the quiescent state coexists with a stable limit cycle of nonlinear coherent oscillations. We explicitly determine the critical coupling constant for this transition.

Design of corona control rings for EHV/UHV line hardwares and substations

The components of EHV/UHV lines and substations can produce significant corona. To limit the consequent Radio Interference and Audible Noise on these systems, suitable corona control rings are employed. The shapes of these rings could vary from circular to rectangular with smooth bends. Many manufacturers seem to adopt trial and error method for arriving at the final design. As such neither the present testing standard nor the final design adopted consider the practical scenario like corona produced by deposition of dirt, bird droppings, etc. The present work aims to make a first step in addressing this practically important problem. This requires an accurate evaluation of the electric field and a reliable method for the evaluation of corona inception. Based on a thorough survey of pertinent literature, the critical avalanche criteria as applicable to large electrodes, has been adopted. Taking the rain drop on the surface as the biggest protrusion, conducting protrusions modeled as semi-ellipsoid is considered as representative for deposition of dust or the boundary of bird droppings etc. Through examples of 4 00 kV and 765 kV class toroidal corona rings, the proposed method is demonstrated. This work is believed to be useful to corona ring manufacturers for EHV/UHV systems.