Stabbing simulations and DNA transfer

Technical developments have made it possible to analyze very low amounts of DNA. This has many advantages, but the drawback of this technological progress is that interpretation of the results becomes increasingly complex: the number of mixed DNA profiles increased relatively to single source DNA profiles and stochastic effects in the DNA profile, such as drop-in and drop-out, are more frequently observed. Moreover, the relevance of low template DNA material regarding the activities alleged is not as straightforward as it was a few years ago, when for example large quantities of blood were recovered. The possibility of secondary and tertiary transfer is now becoming an issue. The purpose of this research is twofold: first, to study the transfer of DNA from the handler and secondly, to observe if handlers would transfer DNA from persons closely connected to them. We chose to mimic cases where the offender would attack a person with a knife. As a first approach, we envisaged that the defense would not give an alternative explanation for the origin of the DNA. In our transfer experiments (4 donors, 16 experiments each, 64 traces), 3% of the traces were single DNA profiles. Most of the time, the DNA profile of the person handling the knife was present as the major profile: in 83% of the traces the major contributor profile corresponded to the stabber's DNA profile (in single stains and mixtures). Mixture with no clear major/minor fraction (12%) were observed. 5% of the traces were considered of insufficient quality (more than 3 contributors, presence of a few minor peaks). In that case, we considered that the stabber's DNA was absent. In our experiments, no traces allowed excluding the stabber, however it must be noted that precautions were taken to minimize background DNA as knives were cleaned before the experiments. DNA profiles of the stabber's colleagues were not observed. We hope that this study will allow for a better understanding of the transfer mechanism and of how to assess and describe results given activity level propositions. In this preliminary research, we have focused on the transfer of DNA on the hand of the person. Besides, more research is needed to assign the probability of the results given an alternative activity proposed by the defense, for instance when the source of the DNA is not contested, but that the activities are.

Deposition and characterization of lines printed through laser-induced forward transfer

The possibility of printing two-dimensional micropatterns of biomolecule solutions is of great interest in many fields of research in biomedicine, from cell-growth and development studies to the investigation of the mechanisms of communication between cells. Although laser-induced forward transfer (LIFT) has been extensively used to print micrometric droplets of biological solutions, the fabrication of complex patterns depends on the feasibility of the technique to print micron-sized lines of aqueous solutions. In this study we investigate such a possibility through the analysis of the influence of droplet spacing of a water and glycerol solution on the morphology of the features printed by LIFT. We prove that it is indeed possible to print long and uniform continuous lines by controlling the overlap between adjacent droplets. We show how, depending on droplet spacing, several printed morphologies are generated, and we offer, in addition, a simple explanation of the observed behavior based on the jetting dynamics characteristic of the LIFT of liquids.

Molecular Physics of Elementary Processes relevant to Hypersonics: atom-molecule, molecule-molecule and atom-surface processes.

In the present chapter some prototype gas and gas-surface processes occurring within the hypersonic flow layer surrounding spacecrafts at planetary entry are discussed. The discussion is based on microscopic dynamical calculations of the detailed cross sections and rate coefficients performed using classical mechanics treatments for atoms, molecules and surfaces. Such treatment allows the evaluation of the efficiency of thermal processes (both at equilibrium and nonequilibrium distributions) based on state-to-state and state specific calculations properly averaged over the population of the initial states. The dependence of the efficiency of the considered processes on the initial partitioning of energy among the various degrees of freedom is discussed.

Total synthesis of entecavir

Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.

Le Bloc républicain du Gâtinais : organe des partis radical-socialiste et socialiste ["puis" organe des radicaux, radicaux-socialistes et socialistes], paraissant le samedi

1906/04/07 (A1,N4).

Radiative Heat Transfer in Boiler Furnaces

Better models are needed for radiative heat transfer in boiler furnaces. If the process is known better, combustion in the furnace can be optimized to produce low emissions. It makes the process to be environmental friendly. Furthermore, if there is a better model of the furnace it can more fully explain what is happening inside the furnace. Using of the model one can quickly and easily analyze how it operates with bio fuels, moist fuels or difficult fuels and improve the operation. Models helps with better estimation of furnace dimensions and result in more accurate understanding of operation. Key component lacking in these models is radiative heat transfer in particle laden gases. If there are no particles than radiative heat transfer can be calculated approximately. There are two problems with current models when used with flow modeling. The first one is a need to account for a particle laden gas and the second one is an absence of a fast algorithm. Fast calculation is needed if radiative heat transfer calculation is done for a large CDF model. Computations slow down if time is required for calculating radiative properties over and over again. This thesis presents a band model for radiative heat transfer in boiler furnaces. Advantage is a quickness of calculation and account of particles in the process.

The use of future-oriented knowledge in regional innovation processes: Research on knowledge generation, transfer and conversion

The importance of the regional level in research has risen in the last few decades and a vast literature in the fields of, for instance, evolutionary and institutional economics, network theories, innovations and learning systems, as well as sociology, has focused on regional level questions. Recently the policy makers and regional actors have also began to pay increasing attention to the knowledge economy and its needs, in general, and the connectivity and support structures of regional clusters in particular. Nowadays knowledge is generally considered as the most important source of competitive advantage, but even the most specialised forms of knowledge are becoming a short-lived resource for example due to the accelerating pace of technological change. This emphasizes the need of foresight activities in national, regional and organizational levels and the integration of foresight and innovation activities. In regional setting this development sets great challenges especially in those regions having no university and thus usually very limited resources for research activities. Also the research problem of this dissertation is related to the need to better incorporate the information produced by foresight process to facilitate and to be used in regional practice-based innovation processes. This dissertation is a constructive case study the case being Lahti region and a network facilitating innovation policy adopted in that region. Dissertation consists of a summary and five articles and during the research process a construct or a conceptual model for solving this real life problem has been developed. It is also being implemented as part of the network facilitating innovation policy in the Lahti region.

Coolant Flow and Heat Transfer in Pebble-Bed Reactor Core

This thesis gathers knowledge about ongoing high-temperature reactor projects around the world. Methods for calculating coolant flow and heat transfer inside a pebble-bed reactor core are also developed. The thesis begins with the introduction of high-temperature reactors including the current state of the technology. Process heat applications that could use the heat from a high-temperature reactor are also introduced. A suitable reactor design with data available in literature is selected for the calculation part of the thesis. Commercial computational fluid dynamics software Fluent is used for the calculations. The pebble-bed is approximated as a packed-bed, which causes sink terms to the momentum equations of the gas flowing through it. A position dependent value is used for the packing fraction. Two different models are used to calculate heat transfer. First a local thermal equilibrium is assumed between the gas and solid phases and a single energy equation is used. In the second approach, separate energy equations are used for the phases. Information about steady state flow behavior, pressure loss, and temperature distribution in the core is obtained as results of the calculations. The effect of inlet mass flow rate to pressure loss is also investigated. Data found in literature and the results correspond each other quite well, considered the amount of simplifications in the calculations. The models developed in this thesis can be used to solve coolant flow and heat transfer in a pebble-bed reactor, although additional development and model validation is needed for better accuracy and reliability.

Modeling reaction kinetics and mass transfer in ozonation in water solutions

This dissertation is based on four articles dealing with modeling of ozonation. The literature part of this considers some models for hydrodynamics in bubble column simulation. A literature review of methods for obtaining mass transfer coefficients is presented. The methods presented to obtain mass transfer are general models and can be applied to any gas-liquid system. Ozonation reaction models and methods for obtaining stoichiometric coefficients and reaction rate coefficients for ozonation reactions are discussed in the final section of the literature part. In the first article, ozone gas-liquid mass transfer into water in a bubble column was investigated for different pH values. A more general method for estimation of mass transfer and Henry’s coefficient was developed from the Beltrán method. The ozone volumetric mass transfer coefficient and the Henry’s coefficient were determined simultaneously by parameter estimation using a nonlinear optimization method. A minor dependence of the Henry’s law constant on pH was detected at the pH range 4 - 9. In the second article, a new method using the axial dispersion model for estimation of ozone self-decomposition kinetics in a semi-batch bubble column reactor was developed. The reaction rate coefficients for literature equations of ozone decomposition and the gas phase dispersion coefficient were estimated and compared with the literature data. The reaction order in the pH range 7-10 with respect to ozone 1.12 and 0.51 the hydroxyl ion were obtained, which is in good agreement with literature. The model parameters were determined by parameter estimation using a nonlinear optimization method. Sensitivity analysis was conducted using object function method to obtain information about the reliability and identifiability of the estimated parameters. In the third article, the reaction rate coefficients and the stoichiometric coefficients in the reaction of ozone with the model component p-nitrophenol were estimated at low pH of water using nonlinear optimization. A novel method for estimation of multireaction model parameters in ozonation was developed. In this method the concentration of unknown intermediate compounds is presented as a residual COD (chemical oxygen demand) calculated from the measured COD and the theoretical COD for the known species. The decomposition rate of p-nitrophenol on the pathway producing hydroquinone was found to be about two times faster than the p-nitrophenol decomposition rate on the pathway producing 4- nitrocatechol. In the fourth article, the reaction kinetics of p-nitrophenol ozonation was studied in a bubble column at pH 2. Using the new reaction kinetic model presented in the previous article, the reaction kinetic parameters, rate coefficients, and stoichiometric coefficients as well as the mass transfer coefficient were estimated with nonlinear estimation. The decomposition rate of pnitrophenol was found to be equal both on the pathway producing hydroquinone and on the path way producing 4-nitrocathecol. Comparison of the rate coefficients with the case at initial pH 5 indicates that the p-nitrophenol degradation producing 4- nitrocathecol is more selective towards molecular ozone than the reaction producing hydroquinone. The identifiability and reliability of the estimated parameters were analyzed with the Marcov chain Monte Carlo (MCMC) method. @All rights reserved. No part of the publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the author.

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

Nanoparticle Labels in Bioaffinity Assays

Nanoparticles offer adjustable and expandable reactive surface area compared to the more traditional solid phase forms utilized in bioaffinity assays due to the high surface to-volume ratio. The versatility of nanoparticles is further improved by the ability to incorporate various molecular complexes such as luminophores into the core. Nanoparticle labels composed of polystyrene, silica, inorganic crystals doped with high number of luminophores, preferably lanthanide(III) complexes, are employed in bioaffinity assays. Other label species such as semiconductor crystals (quantum dots) or colloidal gold clusters are also utilized. The surface derivatization of such particles with biomolecules is crucial for the applicability to bioaffinity assays. The effectiveness of a coating is reliant on the biomolecule and particle surface characteristics and the selected coupling technique. The most critical aspects of the particle labels in bioaffinity assays are their size-dependent features. For polystyrene, silica and inorganic phosphor particles, these include the kinetics, specific activity and colloidal stability. For quantum dots and gold colloids, the spectral properties are also dependent on particle size. This study reports the utilization of europium(III)-chelate-embedded nanoparticle labels in the development of bioaffinity assays. The experimental covers both the heterogeneous and homogeneous assay formats elucidating the wide applicability of the nanoparticles. It was revealed that the employment of europium(III) nanoparticles in heterogeneous assays for viral antigens, adenovirus hexon and hepatitis B surface antigen (HBsAg), resulted in sensitivity improvement of 10-1000 fold compared to the reference methods. This improvement was attributed to the extreme specific activity and enhanced monovalent affinity of the nanoparticles conjugates. The applicability of europium(III)-chelate-doped nanoparticles to homogeneous assay formats were proved in two completely different experimental settings; assays based on immunological recognition or proteolytic activity. It was shown that in addition to small molecule acceptors, particulate acceptors may also be employed due to the high specific activity of the particles promoting proximity-induced reabsorptive energy transfer in addition to non-radiative energy transfer. The principle of proteolytic activity assay relied on a novel dual-step FRET concept, wherein the streptavidin-derivatized europium(III)-chelate-doped nanoparticles were used as donors for peptide substrates modified with biotin and terminal europium emission compliant primary acceptor and a secondary quencher acceptor. The recorded sensitized emission was proportional to the enzyme activity, and the assay response to various inhibitor doses was in agreement with those found in literature showing the feasibility of the technique. Experiments regarding the impact of donor particle size on the extent of direct donor fluorescence and reabsorptive excitation interference in a FRET-based application was conducted with differently sized europium(III)-chelate-doped nanoparticles. It was shown that the size effect was minimal

Tautomerism and Fragmentation of Biologically Active Hetero Atom (O, N)-Containing Acyclic and Cyclic Compounds Under Electron Ionization

In this thesis a total of 86 compounds containing the hetero atoms oxygen and nitrogen were studied under electron ionization mass spectrometry (EIMS). These compounds are biologically active and were synthesized by various research groups. The main attention of this study was paid on the fragmentations related to different tautomeric forms of 2- phenacylpyridines, 2-phenacylquinolines, 8-aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo- [2,1-c][1,2,4]triazines and aryl- and benzyl-substituted 2,3-dihydroimidazo[1,2-a]pyrimidine-5,7-(1H,6H)-diones. Also regio/stereospecific effects on fragmentations of pyrrolo- and isoindoloquinazolinones and naphthoxazine, naphthpyrrolo-oxazinone and naphthoxazino-benzoxazine derivatives were screened. Results were compared with NMR data, when available. The first part of thesis consists of theory and literature review of different types of tautomerism and fragmentation mechanisms in EIMS. The effects of tautomerism in biological systems are also briefly reviewed. In the second part of the thesis the own results of the author, based on six publications,are discussed. For 2-phenacylpyridines and 2-phenacylquinolines the correlation of different Hammett substituent constants to the relative abundances (RA) or total ion currents (% TIC) of selected ions were investigated. Although it was not possible to assign most of the ions formed unambiguously to the different tautomers, the linear fits of their RAs and % TICs can be related to changing contributions of different tautomeric forms. For dioxoimidazotriazines and imidazopyrimidinediones the effects of substituents were rather weak. The fragmentations were also found useful for obtaining structural information. Some stereoisomeric pairs of pyrrolo- and isoindoloquinazolines and regiomeric pairs of naphtoxazine derivatives showed clear differences in thir mass spectra. Some mechanisms are suggested for their fragmentations.

Enantioselective synthesis of aziridines using asymmetric transfer hydrogenation as a precursor for chiral derivatives used as bonding agent for rocket solid propellants

A rapid, expedient and enantioselective method for the synthesis of beta-hydroxy amines and monosubstituted aziridines in up to 99% e.e., via asymmetric transfer hydrogenation of a-amino ketones and cyclisation through treatment with tosyl chloride and base, is described. (1R,2R)-N-(para-toluenesulfonyl)-1,2-ethylenediamine with formic acid has been utilised as a ligand for the Ruthenium (II) catalysed enantioselective transfer hydrogenation of the ketones.The chiral 2-methyl aziridine, which is a potentially more efficient bonding agent for Rocket Solid Propellant has been successfully achieved.

A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15-C16 bond formation

The esterification of fragment C1-C8 (2) with fragment C16-C23 (3) to give iodo derivative 4, followed by a Pd-catalysed coupling with a C9-C15 fragment (7 or 8), may provide a common precursor of most palmerolides. Ligands and reaction conditions were exhaustively examined to perform the C15-C16 bond formation via Negishi reaction. With simple models, pre-activated Pd-Xantphos and Pd-DPEphos complexes were the most efficient catalysts at RT. Zincation of the C9-C15 fragment (8) and cross coupling with 4 required 3 equiv of t-BuLi, 10 mol % of Pd-Xantphos and 60 °C.

Cost Optimisation of Mobile Advertising Client Data Transfer

Data traffic caused by mobile advertising client software when it is communicating with the network server can be a pain point for many application developers who are considering advertising-funded application distribution, since the cost of the data transfer might scare their users away from using the applications. For the thesis project, a simulation environment was built to mimic the real client-server solution for measuring the data transfer over varying types of connections with different usage scenarios. For optimising data transfer, a few general-purpose compressors and XML-specific compressors were tried for compressing the XML data, and a few protocol optimisations were implemented. For optimising the cost, cache usage was improved and pre-loading was enhanced to use free connections to load the data. The data traffic structure and the various optimisations were analysed, and it was found that the cache usage and pre-loading should be enhanced and that the protocol should be changed, with report aggregation and compression using WBXML or gzip.