Mapping hippocampal and ventricular change in Alzheimer disease

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Fifty-two high-resolution MRI scans were acquired from 12 AD patients (age: 68.4 +/- 1.9 years) and 14 matched controls (age: 71.4 +/- 0.9 years), each scanned twice (2.1 +/- 0.4 years apart). 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials. (C) 2004 Elsevier Inc. All rights reserved.

Structure-function studies of the plant cyclotides: The role of a circular protein backbone

The traditional idea of proteins as linear chains of amino acids is being challenged with the discovery of miniproteins that contain a circular backbone. The cyclotide family is the largest group of circular proteins and is characterized by an amide-circularized protein backbone and six conserved cysteine residues. These conserved cysteines are paired to form a knotted network of disulfide bonds. The combination of the circular backbone and a cystine knot, known as the cyclic cystine knot (CCK) motif, confers exceptional stability upon the cyclotides. This review discusses the role of the circular backbone based on studies of both the oxidative folding of kalata B1, the prototypical cyclotide, and a comparison of the structure and activity of kalata B1 and its acyclic permutants.

The 2.1 angstrom crystal structure of the far-red fluorescent protein HcRed: Inherent conformational flexibility of the chromophore

We have determined the crystal structure of HcRed, a far-red fluorescent protein isolated from Heteractis crispa, to 2.1 resolution. HcRed was observed to form a dimer, in contrast to the monomeric form of green fluorescent protein (GFP) or the tetrameric forms of the GFP-like proteins (eqFP611, Rtms5 and DsRed). Unlike the well-defined chromophore conformation observed in GFP and the GFP-like proteins, the HcRed chromophore was observed to be considerably mobile. Within the HcRed structure, the cyclic tripeptide chromophore, Glu64-Tyr65-Gly66, was observed to adopt both a cis coplanar and a tran. non-coplanar conformation. As a result of these two con formations, the hydroxyphenyl moiety of the chromophore makes distinct interactions within the interior of the b-can. These data together with a quantum chemical model of the chromophore, suggest the cis coplanar conformation to be consistent with the fluorescent properties of HcRed, and the trans non-coplanar conformation to be consistent with non-fluorescent properties of hcCP, the chromoprotein parent of HcRed. Moreover, within the GFP-like family, it appears that where conformational freedom is permissible then flexibility in the chromophore conformation is possible. 2005 Elsevier Ltd. All rights reserved.

The cross-entropy method for network reliability estimation

Consider a network of unreliable links, modelling for example a communication network. Estimating the reliability of the network-expressed as the probability that certain nodes in the network are connected-is a computationally difficult task. In this paper we study how the Cross-Entropy method can be used to obtain more efficient network reliability estimation procedures. Three techniques of estimation are considered: Crude Monte Carlo and the more sophisticated Permutation Monte Carlo and Merge Process. We show that the Cross-Entropy method yields a speed-up over all three techniques.

A simple implementation of a normal mixture approach to differential gene expression in multiclass microarrays

Motivation: An important problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. We provide a straightforward and easily implemented method for estimating the posterior probability that an individual gene is null. The problem can be expressed in a two-component mixture framework, using an empirical Bayes approach. Current methods of implementing this approach either have some limitations due to the minimal assumptions made or with more specific assumptions are computationally intensive. Results: By converting to a z-score the value of the test statistic used to test the significance of each gene, we propose a simple two-component normal mixture that models adequately the distribution of this score. The usefulness of our approach is demonstrated on three real datasets.

No pain, no gain? Torture and ethics in the war on terror

Is the use of torture ever justified? This article argues that torture cannot be justified, even in so called ticking bomb cases, but that in such extreme situations it may be necessary. In those situations, judgements about whether the use of torture is legitimate must balance the imminence and gravity of the threat with the need to prevent future occurrences of torture and maintain a normative environment that is hostile to its use. The article begins by observing that the use of torture and/or cruel and degrading treatment has become a core component of the global war on terror. It tests the claim that the use of coercive interrogation techniques does not constitute torture, showing that similar arguments were levelled by both the British and French governments in relation to Northern Ireland and Algeria respectively and found wanting. It then evaluates and rejects Dershowitz's claim for the legalization of torture and the more limited claim that torture may be permissible in ticking bomb scenarios. In the final section, the article questions how we might maintain the prohibition on torture while acknowledging that it may be necessary in some hypothetical cases.

Random field models and priors on wind

This report seeks to make concrete some of the ideas we have been discussing about sensible priors for winds over the ocean. In particular, random field models are reviewed, as are permissible covariance functions. The criteria which these covariance functions must satisfy in order that vorticity and divergence exist and are continuous are defined. The use of Helmholtz theorem is discussed, and possible choices for the covariances are suggested.

Evaluating the capacity of long haul soliton transmission

We review recent developments in the use of optical solitons for communication systems spanning transoceanic distances. The implementation of "soliton control" to alleviate the detrimental impact of effects such as amplifier noise is shown to be critical for obtaining advantages over competing technologies. The potential performance of two control strategies, namely straight line filtering and synchronous phase modulation, is examined in detail. Design diagrams are used to determine the maximum permissible amplifier spacing, which is a key determinant of system economics. To focus the enquiry, two example system spans are taken, representing transatlantic and transpacific distances. It is concluded that straight line filtering provides very little improvement over a basic design without control. However synchronous phase modulation, which may be implemented using a handful of actively driven components, provides very substantial benefits. These may be used either to extend the overall bit-rate-distance product of the system or to increase the amplifier spacing at more moderate capacities.

The electron optical limits of performance of single-polepiece magnetic electron lenses

The thesis is concerned with the electron properties of single-polepiece magnetic electron lenses especially under conditions of extreme polepiece saturation. The electron optical properties are first analysed under conditions of high polepiece permeability. From this analysis, a general idea can be obtained of the important parameters that affect ultimate lens performance. In addition, useful information is obtained concerning the design of improved lenses operating under conditions of extreme polepiece saturation, for example at flux densities of the order of 10 Tesla. It is shown that in a single-polepiece lens , the position and shape of the lens exciting coil plays an important role. In particular, the maximum permissible current density in the windings,rather than the properties of the iron, can set a limit to lens performance. This factor was therefore investigated in some detail. The axial field distribution of a single-polepiece lens, unlike that of a conventional lens, is highly asymmetrical. There are therefore two possible physical arrangements of the lens with respect to the incoming electron beam. In general these two orientations will result in different aberration coefficients. This feature has also been investigated in some detail. Single-pole piece lenses are thus considerably more complicated electron- optically than conventional double polepiece lenses. In particular, the absence of the usual second polepiece causes most of the axial magnetic flux density distribution to lie outside the body of the lens. This can have many advantages in electron microscopy but it creates problems in calculating the magnetic field distribution. In particular, presently available computer programs are liable to be considerably in error when applied to such structures. It was therefore necessary to find independent ways of checking the field calculations. Furthermore, if the polepiece is allowed to saturate, much more calculation is involved since the field distribution becomes a non-linear function of the lens excitation. In searching for optimum lens designs, care was therefore taken to ensure that the coil was placed in the optimum position. If this condition is satisfied there seems to be no theoretical limit to the maximum flux density that can be attained at the polepiece tip. However , under iron saturation condition, some broadening of the axial field distribution will take place, thereby changing the lens aberrations . Extensive calculations were therefore made to find the minimum spherical and chromatic aberration coefficients . The focal properties of such lens designs are presented and compared with the best conventional double-polepiece lenses presently available.

The pro-reform movement led by Avenir de la Francaise:a point of leverage in the French political process?

The study examines factors influencing language planning decisions in contemporary France. It focuses upon the period 1992-1994, which witnessed the introduction of two major language policy measures, the first an amendment to the French Constitution, in 1992, proclaiming the language of the Republic as French, the second, in 1994, legislation to extend the ambit of the loi Bas-Lauriol, governing the use of the French language in France. The thesis posits a significant role for the pro-reform movement led by the French language association Avenir de la Langue Francaise (ALF) in the introduction and formulation of the policy measures concerned. The movement is depicted as continuing the traditional pattern of intellectual involvement in language planning, whilst also marking the beginning of a highly proactive, and increasingly political approach. Detailed examination of the movement's activities reveals that contextual factors and strategic strength combined to facilitate access to the levers of power, and enabled those involved to exert an impact on policy initiation, formulation, and ultimately implementation. However, ALF's decision to pursue the legislative route led to the expansion of the network of actors involved in language policymaking, and the development of counter-pressure from sectoral groups. It is suggested that this more interventionist approach destabilised the traditionally consensual language policy community, and called into question the quasi-monopoly of the intelligentsia in respect of language policymaking. It raised broader questions relating to freedom of expression and the permissible limits of language regulation in a democracy such as France. It also exposed ongoing ambiguities and inconsistencies in the interpretation of the tenets of language planning.

Evaluating the Capacity of Phase Modulator-Controlled Long-Haul Soliton Transmission

We review recent developments in the use of optical solitons for communication systems spanning transoceanic distances. The implementation of "soliton control" to alleviate the detrimental impact of effects such as amplifier noise is shown to be critical for obtaining advantages over competing technologies. The potential performance of two control strategies, namely straight line filtering and synchronous phase modulation, is examined in detail. Design diagrams are used to determine the maximum permissible amplifier spacing, which is a key determinant of system economics. To focus the enquiry, two example system spans are taken, representing transatlantic and transpacific distances. It is concluded that straight line filtering provides very little improvement over a basic design without control. However synchronous phase modulation, which may be implemented using a handful of actively driven components, provides very substantial benefits. These may be used either to extend the overall bit-rate-distance product of the system or to increase the amplifier spacing at more moderate capacities. © 1995 Academic Press. All rights reserved.

Network effects, network structure and consumer interaction in mobile telecommunications in Europe and Asia

This paper estimates the importance of (tariff-mediated) network effects and the impact of a consumer's social network on her choice of mobile phone provider. The study uses network data obtained from surveys of students in several European and Asian countries. We use the Quadratic Assignment Procedure, a non-parametric permutation test, to adjust for the particular error structure of network data. We find that respondents strongly coordinate their choice of mobile phone providers, but only if their provider induces network effects. This suggests that this coordination depends on network effects rather than on information contagion or pressure to conform to the social environment.

A Computer Algebra Application to Determination of Lie Symmetries of Partial Differential Equations

The paper has been presented at the 12th International Conference on Applications of Computer Algebra, Varna, Bulgaria, June, 2006

On a New Approach to Williamson's Generalization of Pólya's Enumeration Theorem

Pólya’s fundamental enumeration theorem and some results from Williamson’s generalized setup of it are proved in terms of Schur- Macdonald’s theory (S-MT) of “invariant matrices”. Given a permutation group W ≤ Sd and a one-dimensional character χ of W , the polynomial functor Fχ corresponding via S-MT to the induced monomial representation Uχ = ind|Sdv/W (χ) of Sd , is studied. It turns out that the characteristic ch(Fχ ) is the weighted inventory of some set J(χ) of W -orbits in the integer-valued hypercube [0, ∞)d . The elements of J(χ) can be distinguished among all W -orbits by a maximum property. The identity ch(Fχ ) = ch(Uχ ) of both characteristics is a consequence of S-MT, and is equivalent to a result of Williamson. Pólya’s theorem can be obtained from the above identity by the specialization χ = 1W , where 1W is the unit character of W.

Realization of an Optimal Schedule for the Two-machine Flow-Shop with Interval Job Processing Times

Non-preemptive two-machine flow-shop scheduling problem with uncertain processing times of n jobs is studied. In an uncertain version of a scheduling problem, there may not exist a unique schedule that remains optimal for all possible realizations of the job processing times. We find necessary and sufficient conditions (Theorem 1) when there exists a dominant permutation that is optimal for all possible realizations of the job processing times. Our computational studies show the percentage of the problems solvable under these conditions for the cases of randomly generated instances with n ≤ 100 . We also show how to use additional information about the processing times of the completed jobs during optimal realization of a schedule (Theorems 2 – 4). Computational studies for randomly generated instances with n ≤ 50 show the percentage of the two- machine flow-shop scheduling problems solvable under the sufficient conditions given in Theorems 2 – 4.