New Methods for Measuring Transient Interactions Between Proteins and Curved Membranes

Variations in the physical deformation of the plasma membrane play a significant role in the sorting and behavior of the proteins that occupy it. Determining the interplay between membrane curvature and protein behavior required the development and thorough characterization of a model plasma membrane with well defined and localized regions of curvature. This model system consists of a fluid lipid bilayer that is supported by a dye-loaded polystyrene nanoparticle patterned glass substrate. As the physical deformation of the supported lipid bilayer is essential to our understanding of the behavior of the protein occupying the bilayer, extensive characterization of the structure of the model plasma membrane was conducted. Neither the regions of curvature in the vicinity of the polystyrene nanoparticles or the interaction between a lipid bilayer and small patches of curved polystyrene are well understood, so the results of experiments to determine these properties are described. To do so, individual fluorescently labeled proteins and lipids are tracked on this model system and in live cells. New methods for analyzing the resulting tracks and ensemble data are presented and discussed. To validate the model system and analytical methods, fluorescence microscopy was used to image a peripheral membrane protein, cholera toxin subunit B (CTB). These results are compared to results obtained from membrane components that were not expected to show an preference for membrane curvature: an individual fluorescently-labeled lipid, lissamine rhodamine B DHPE, and another protein, streptavidin associated with biotin-labeled DHPE. The observed tendency for cholera toxin subunit B to avoid curved regions of curvature, as determined by new and established analytical methods, is presented and discussed.

New methods in heat flow analysis with application to flight structures.

Mode of access: Internet.

Experimental essays on medical and philosophical subjects : particularly, I. On the fermentation of alimentary mixtures, and digestion of the food. II. On the nature and properties of fixed air. III. On the respective powers, and manner of acting, of the different kinds of antiseptics. IV. On the scurvy ; with a proposal for trying new methods to prevent or cure the same, at sea. V. On the dissolvent power of quick-lime ; and a further investigation of the properties of fixed air /

Mode of access: Internet.

New methods of alkalimetry, and of determining the commercial value of acids and manganese.

Translation of Neue Verfahrungsweisen zur Prüfung der Pottasche und Soda, der Aschen, der Säuren, insbesondere des Essigs so wie Braunsteins auf ihren wahren Gehalt und Handelswerth.

A second series of lessons on the game of chess, containing several new methods of attack and defence for the use of the higher class of players; to which is added, Fifty games at chess actually played, many of which occurred between the author and some of the best players in France and Germany;

Mode of access: Internet.

Generalized methods and solvers for noise removal from piecewise constant signals. II. New methods

Removing noise from signals which are piecewise constant (PWC) is a challenging signal processing problem that arises in many practical scientific and engineering contexts. In the first paper (part I) of this series of two, we presented background theory building on results from the image processing community to show that the majority of these algorithms, and more proposed in the wider literature, are each associated with a special case of a generalized functional, that, when minimized, solves the PWC denoising problem. It shows how the minimizer can be obtained by a range of computational solver algorithms. In this second paper (part II), using this understanding developed in part I, we introduce several novel PWC denoising methods, which, for example, combine the global behaviour of mean shift clustering with the local smoothing of total variation diffusion, and show example solver algorithms for these new methods. Comparisons between these methods are performed on synthetic and real signals, revealing that our new methods have a useful role to play. Finally, overlaps between the generalized methods of these two papers and others such as wavelet shrinkage, hidden Markov models, and piecewise smooth filtering are touched on.

Three New Methods for Computing Subresultant Polynomial Remainder Sequences (PRS’S)

Given the polynomials f, g ∈ Z[x] of degrees n, m, respectively, with n > m, three new, and easy to understand methods — along with the more efficient variants of the last two of them — are presented for the computation of their subresultant polynomial remainder sequence (prs). All three methods evaluate a single determinant (subresultant) of an appropriate sub-matrix of sylvester1, Sylvester’s widely known and used matrix of 1840 of dimension (m + n) × (m + n), in order to compute the correct sign of each polynomial in the sequence and — except for the second method — to force its coefficients to become subresultants. Of interest is the fact that only the first method uses pseudo remainders. The second method uses regular remainders and performs operations in Q[x], whereas the third one triangularizes sylvester2, Sylvester’s little known and hardly ever used matrix of 1853 of dimension 2n × 2n. All methods mentioned in this paper (along with their supporting functions) have been implemented in Sympy and can be downloaded from the link http://inf-server.inf.uth.gr/~akritas/publications/subresultants.py

New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

New methods for movement technique development in cross-country skiing using mathematical models and simulation

This Licentiate Thesis is devoted to the presentation and discussion of some new contributions in applied mathematics directed towards scientific computing in sports engineering. It considers inverse problems of biomechanical simulations with rigid body musculoskeletal systems especially in cross-country skiing. This is a contrast to the main research on cross-country skiing biomechanics, which is based mainly on experimental testing alone. The thesis consists of an introduction and five papers. The introduction motivates the context of the papers and puts them into a more general framework. Two papers (D and E) consider studies of real questions in cross-country skiing, which are modelled and simulated. The results give some interesting indications, concerning these challenging questions, which can be used as a basis for further research. However, the measurements are not accurate enough to give the final answers. Paper C is a simulation study which is more extensive than paper D and E, and is compared to electromyography measurements in the literature. Validation in biomechanical simulations is difficult and reducing mathematical errors is one way of reaching closer to more realistic results. Paper A examines well-posedness for forward dynamics with full muscle dynamics. Moreover, paper B is a technical report which describes the problem formulation and mathematical models and simulation from paper A in more detail. Our new modelling together with the simulations enable new possibilities. This is similar to simulations of applications in other engineering fields, and need in the same way be handled with care in order to achieve reliable results. The results in this thesis indicate that it can be very useful to use mathematical modelling and numerical simulations when describing cross-country skiing biomechanics. Hence, this thesis contributes to the possibility of beginning to use and develop such modelling and simulation techniques also in this context.

Restoration ecology of coastal lagoons: new methods for the prediction of ecological trajectories and economic valuation

Conservation of the seven lagoons of the Palavas complex (southern France) has been severely impaired by nutrient over-enrichment during at least four decades. The effluents of the Montpellier wastewater treatment plant (WWTP) represented the main nutrient input. To improve the water quality of these lagoons, this WWTP was renovated and upgraded and, since the end of 2005, its effluents have been discharged 11 km offshore into the Mediterranean (total investment €150 M). Possibilities of ecosystem restoration as part of a conservation programme were explored by a focus group of experts. Their tasks were: (i) to evaluate the impact of the reduction of the nutrient input; (ii) if necessary, to design additional measures for an active restoration programme; and (iii) to predict ecosystem trajectories for the different cases. Extension of Magnoliophyta meadows can be taken as a proxy for ecosystem restoration as they favour the increase of several fish (seahorse) and bird (ducks, swans, herons) species, albeit they represent a trade-off for greater flamingos. Additional measures for active ecosystem restoration were only recommended for the most impaired lagoon Méjean, while the least impaired lagoon Ingril is already on a trajectory of spontaneous recovery. A multiple contingent valuation considering four different management options for the Méjean lagoon was used in a pilot study based on face-to-face interviews with 159 respondents. Three levels of ecosystem restoration were expressed in terms of recovery of Magnoliophyta meadows, including their impact on emblematic fish and avifauna. These were combined with different options for access (status quo, increasing access, increasing access with measures to reduce disturbance). The results show a willingness of local populations to pay per year about €25 for the highest level of ecological restoration, while they were only willing to allocate about €5 for additional footpaths and hides.