Bayesian refinement of association signals for 14 loci in 3 common diseases

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies. © 2012 Nature America, Inc. All rights reserved.

Borrowing from the geeks: What can healthcare facility design learn from IT?

People get into healthcare because they want to help society. And when a new hospital is briefed, everyone tries to do their best, but the process is mired by the impossibility of the task. Stakeholders rarely understand the architectural process, nobody can predict the future, and the only thing for certain is that everything will change as the project unfolds, revealing errors in initial assumptions and calculations, shifts in needs, new technologies etc. Yet there’s always pressure to keep to the programme and to press on regardless. This chaos leads eventually to suboptimal results: hospitals the world over are riddled with inefficiencies, idiosyncrasies, incredible wastage and features that lead to poor clinical outcomes. This talk will sketch out the basics of Scrum, the most popular open-source Lean/Agile methodology. It will discuss what healthcare designers can learn from the geeks in Silicon Valley reduce risk, meet deadlines and deliver the highest possible value for the budget despite the uncertainty.

Singularity-free path planning for the Stewart platform manipulator

This paper addresses the problem of singularity-free path planning for the six-degree-of-freedom parallel manipulator known as the Stewart platform manipulator. Unlike serial manipulators, the Stewart platform possesses singular configurations within the workspace where the manipulator is uncontrollable. An algorithm has been developed to construct continuous paths within the workspace of the manipulator by avoiding singularities and ill-conditioning. Given two end-poses of the manipulator, the algorithm finds out safe (well-conditioned) via points and plans a continuous path from the initial pose to the final one. When the two end-poses belong to different branches and no singularity-free path is possible, the algorithm indicates the impossibility of a valid path. A numerical example has also been presented as illustration of the path planning strategy.

Bounds on isoperimetric values of trees

Let G = (V, E) be a finite, simple and undirected graph. For S subset of V, let delta(S, G) = {(u, v) is an element of E : u is an element of S and v is an element of V - S} be the edge boundary of S. Given an integer i, 1 <= i <= vertical bar V vertical bar, let the edge isoperimetric value of G at i be defined as b(e)(i, G) = min(S subset of V:vertical bar S vertical bar=i)vertical bar delta(S, G)vertical bar. The edge isoperimetric peak of G is defined as b(e)(G) = max(1 <= j <=vertical bar V vertical bar)b(e)(j, G). Let b(v)(G) denote the vertex isoperimetric peak defined in a corresponding way. The problem of determining a lower bound for the vertex isoperimetric peak in complete t-ary trees was recently considered in [Y. Otachi, K. Yamazaki, A lower bound for the vertex boundary-width of complete k-ary trees, Discrete Mathematics, in press (doi: 10.1016/j.disc.2007.05.014)]. In this paper we provide bounds which improve those in the above cited paper. Our results can be generalized to arbitrary (rooted) trees. The depth d of a tree is the number of nodes on the longest path starting from the root and ending at a leaf. In this paper we show that for a complete binary tree of depth d (denoted as T-d(2)), c(1)d <= b(e) (T-d(2)) <= d and c(2)d <= b(v)(T-d(2)) <= d where c(1), c(2) are constants. For a complete t-ary tree of depth d (denoted as T-d(t)) and d >= c log t where c is a constant, we show that c(1)root td <= b(e)(T-d(t)) <= td and c(2)d/root t <= b(v) (T-d(t)) <= d where c(1), c(2) are constants. At the heart of our proof we have the following theorem which works for an arbitrary rooted tree and not just for a complete t-ary tree. Let T = (V, E, r) be a finite, connected and rooted tree - the root being the vertex r. Define a weight function w : V -> N where the weight w(u) of a vertex u is the number of its successors (including itself) and let the weight index eta(T) be defined as the number of distinct weights in the tree, i.e eta(T) vertical bar{w(u) : u is an element of V}vertical bar. For a positive integer k, let l(k) = vertical bar{i is an element of N : 1 <= i <= vertical bar V vertical bar, b(e)(i, G) <= k}vertical bar. We show that l(k) <= 2(2 eta+k k)

Separability in relativistic Hamiltonian particle dynamics

The problem of separability in recent models of classical relativistic interacting particles is examined. This physical requirement is shown to be more subtle than naive separability of all the constraints defining the system: it is adequate to be able to canonically transform the time-fixing constraints from an unseparated to a separated form when clusters emerge. Viewing separability in this way, and within a specific framework, we are led to a new no-interaction theorem which states the incompatibility of nontrivial interaction with relativistic invariance, separability, and invariant world lines for more than two particles.

Problems of Proto-Slavic Historical Nominal Morphology : On the Basis of Old Church Slavic

In this study I offer a diachronic solution for a number of difficult inflectional endings in Old Church Slavic nominal declensions. In this context I address the perhaps most disputed and the most important question of the Slavic nominal inflectional morphology: whether there was in Proto-Slavic an Auslautgesetz (ALG), a law of final syllables, that narrowed the Proto-Indo-European vowel */o/ to */u/ in closed word-final syllables. In addition, the work contains an exhaustive morphological classification of the nouns and adjectives that occur in canonical Old Church Slavic. I argue that Proto-Indo-European */o/ became Proto-Slavic */u/ before word-final */s/ and */N/. This conclusion is based on the impossibility of finding credible analogical (as opposed to phonological) explanations for the forms supporting the ALG hypothesis, and on the survival of the neuter gender in Slavic. It is not likely that the */o/-stem nominative singular ending */-u/ was borrowed from the accusative singular, because the latter would have been the only paradigmatic form with the stem vowel */-u-/. It is equally unlikely that the ending */-u/ was borrowed from the */u/-stems, because the latter constituted a moribund class. The usually stated motivation for such an analogical borrowing, i.e. a need to prevent the merger of */o/-stem masculines with neuters of the same class, is not tenable. Extra-Slavic, as well as intra-Slavic evidence suggests that phonologically-triggered mergers between two semantically opaque genders do not tend to be prevented, but rather that such mergers lead to the loss of the gender opposition in question. On the other hand, if */-os/ had not become */-us/, most nouns and, most importantly, all adjectives and pronouns would have lost the formal distinction between masculines and neuters. This would have necessarily resulted in the loss of the neuter gender. A new explanation is given for the most apparent piece of evidence against the ALG hypothesis, the nominative-accusative singular of the */es/-stem neuters, e.g. nebo 'sky'. I argue that it arose in late Proto-Slavic dialects, replacing regular nebe, under the influence of the */o/- and */yo/-stems where a correlation had emerged between a hard root-final consonant and the termination -o, on the one hand, and a soft root-final consonant and the termination -e, on the other.

Do H-functions always increase during Violent Relaxation

Recent work on the violent relaxation of collisionless stellar systems has been based on the notion of a wide class of entropy functions. A theorem concerning entropy increase has been proved. We draw attention to some underlying assumptions that have been ignored in the applications of this theorem to stellar dynamical problems. Once these are taken into account, the use of this theorem is at best heuristic. We present a simple counter-example.

Classical Langevin dynamics of a charged particle moving on a sphere and diamagnetism: A surprise

It is generally known that the orbital diamagnetism of a classical system of charged particles in thermal equilibrium is identically zero —the Bohr-van Leeuwen theorem. Physically, this null result derives from the exact cancellation of the orbital diamagnetic moment associated with the complete cyclotron orbits of the charged particles by the paramagnetic moment subtended by the incomplete orbits skipping the boundary in the opposite sense. Motivated by this crucial but subtle role of the boundary, we have simulated here the case of a finite but unbounded system, namely that of a charged particle moving on the surface of a sphere in the presence of an externally applied uniform magnetic field. Following a real space-time approach based on the classical Langevin equation, we have computed the orbital magnetic moment that now indeed turns out to be non-zero and has the diamagnetic sign. To the best of our knowledge, this is the first report of the possibility of finite classical diamagnetism in principle, and it is due to the avoided cancellation.

Truth, Proof and Gödelian Arguments : A Defence of Tarskian Truth in Mathematics

One of the most fundamental questions in the philosophy of mathematics concerns the relation between truth and formal proof. The position according to which the two concepts are the same is called deflationism, and the opposing viewpoint substantialism. In an important result of mathematical logic, Kurt Gödel proved in his first incompleteness theorem that all consistent formal systems containing arithmetic include sentences that can neither be proved nor disproved within that system. However, such undecidable Gödel sentences can be established to be true once we expand the formal system with Alfred Tarski s semantical theory of truth, as shown by Stewart Shapiro and Jeffrey Ketland in their semantical arguments for the substantiality of truth. According to them, in Gödel sentences we have an explicit case of true but unprovable sentences, and hence deflationism is refuted. Against that, Neil Tennant has shown that instead of Tarskian truth we can expand the formal system with a soundness principle, according to which all provable sentences are assertable, and the assertability of Gödel sentences follows. This way, the relevant question is not whether we can establish the truth of Gödel sentences, but whether Tarskian truth is a more plausible expansion than a soundness principle. In this work I will argue that this problem is best approached once we think of mathematics as the full human phenomenon, and not just consisting of formal systems. When pre-formal mathematical thinking is included in our account, we see that Tarskian truth is in fact not an expansion at all. I claim that what proof is to formal mathematics, truth is to pre-formal thinking, and the Tarskian account of semantical truth mirrors this relation accurately. However, the introduction of pre-formal mathematics is vulnerable to the deflationist counterargument that while existing in practice, pre-formal thinking could still be philosophically superfluous if it does not refer to anything objective. Against this, I argue that all truly deflationist philosophical theories lead to arbitrariness of mathematics. In all other philosophical accounts of mathematics there is room for a reference of the pre-formal mathematics, and the expansion of Tarkian truth can be made naturally. Hence, if we reject the arbitrariness of mathematics, I argue in this work, we must accept the substantiality of truth. Related subjects such as neo-Fregeanism will also be covered, and shown not to change the need for Tarskian truth. The only remaining route for the deflationist is to change the underlying logic so that our formal languages can include their own truth predicates, which Tarski showed to be impossible for classical first-order languages. With such logics we would have no need to expand the formal systems, and the above argument would fail. From the alternative approaches, in this work I focus mostly on the Independence Friendly (IF) logic of Jaakko Hintikka and Gabriel Sandu. Hintikka has claimed that an IF language can include its own adequate truth predicate. I argue that while this is indeed the case, we cannot recognize the truth predicate as such within the same IF language, and the need for Tarskian truth remains. In addition to IF logic, also second-order logic and Saul Kripke s approach using Kleenean logic will be shown to fail in a similar fashion.

Asymptotic behaviour of point processes with Markov-dependent intervals

This splitting techniques for MARKOV chains developed by NUMMELIN (1978a) and ATHREYA and NEY (1978b) are used to derive an imbedded renewal process in WOLD's point process with MARKOV-correlated intervals. This leads to a simple proof of renewal theorems for such processes. In particular, a key renewal theorem is proved, from which analogues to both BLACKWELL's and BREIMAN's forms of the renewal theorem can be deduced.

Forms of relativistic dynamics with World Line Condition and separability

he Dirac generator formalism for relativistic Hamiltonian dynamics is reviewed along with its extension to constraint formalism. In these theories evolution is with respect to a dynamically defined parameter, and thus time evolution involves an eleventh generator. These formulations evade the No-Interaction Theorem. But the incorporation of separability reopens the question, and together with the World Line Condition leads to a second no-interaction theorem for systems of three or more particles. Proofs are omitted, but the results of recent research in this area is highlighted.

Ajan sisäkkäiset tilat. Arkkitehtuuri, valokuva ja menneisyyden esittäminen W. G. Sebaldin romaanissa Austerlitz

In her thesis, Kaisa Kaakinen analyzes how the German emigrant author W. G. Sebald (1944-2001) uses architecture and photography in his last novel "Austerlitz" to represent time, history and remembering. Sebald describes time in spatial terms: it is like a building, the rooms and chambers of which are connected to each other. The poetics of spatial time manifests itself on multiple levels of the text. Kaakinen traces it in architectural representations, photographic images, intertextuality, as well as in the form of the text, using the concept of spatial form by Joseph Frank. Architectural and photographic representations serve as meeting points for different aspects and angles of the novel and illustrate the idea of a layered present that has multiple connections to the past. The novel tells a story of Jacques Austerlitz, who as a small child was sent from Prague to Britain in one of the so-called Kindertransports that saved children from Central Europe occupied by the National Socialists. Only gradually he remembers his Jewish parents, who have most likely perished in Nazi concentration camps. The novel brings the problematic of writing about another person's past to the fore by the fact that Austerlitz's story is told by an anonymous narrator, Austerlitz's interlocutor, who listens to and writes down Austerlitz's story. Kaakinen devotes the final part of her thesis to study the demands of representing a historical trauma, drawing on authors such as Dominick LaCapra and Michael Rothberg. Through the analysis of architectural and photographic representations in the novel, she demonstrates how Austerlitz highlights the sense of singularity and inaccessibility of memories of an individual, while also stressing the necessity - and therefore a certain kind of possibility - of passing these memories to another person. The coexistence of traumatic narrowness and of the infinity of history is reflected in ambivalent buildings. Some buildings in the novel resemble reversible figures: they can be perceived simultaneously as ruins and as construction sites. Buildings are also shown to be able to both cover and preserve memories - an idea that also is repeated in the use of photography, which tends to both replace memories and cause an experience of the presence of an absent thing. Commenting and critisizing some recent studies on Sebald, the author develops a reading which stresses the ambivalence inherent in Sebald's view on history and historiography. Austerlitz shows the need to recognize the inevitable absence of the past as well as the distance from the experiences of others. Equally important, however, is the refusal to give up narrating the past: Sebald's novel stresses the necessity to preserve the sites of the past, which carry silent traces of vanished life. The poetics of Austerlitz reflects the paradox of the simultaneous impossibility and indispensability of writing history.

On the invariants of coloured Petri Nets

In this paper, we develop a theorem that enables computation of the place invariants of the union of a finite collection of coloured Petri Nets when the individual nets satisfy certain conditions and their invariants are known. We consider the illustrative examples of the Readers-Writers problem, a resource sharing system, and a network of databases and show how this theorem is a valuable tool in the analysis of concurrent systems.

Spontaneous symmetry breaking in twisted noncommutative quantum theories

We analyze aspects of symmetry breaking for Moyal spacetimes within a quantization scheme which preserves the twisted Poincare´ symmetry. Towards this purpose, we develop the Lehmann-Symanzik- Zimmermann (LSZ) approach for Moyal spacetimes. The latter gives a formula for scattering amplitudes on these spacetimes which can be obtained from the corresponding ones on the commutative spacetime. This formula applies in the presence of spontaneous breakdown of symmetries as well. We also derive Goldstone’s theorem on Moyal spacetime. The formalism developed here can be directly applied to the twisted standard model.

Application of Maclaurin Series in Structural Analysis

In the simple theory of flexure of beams, the slope, bending moment, shearing force, load and other quantities are functions of a derivative of y with respect to x. It is shown that the elastic curve of a transversely loaded beam can be represented by the Maclaurin series. Substitution of the values of the derivatives gives a direct solution of beam problems. In this paper the method is applied to derive the Theorem or three moments and slope deflection equations. The method is extended to the solution of a rigid portal frame. Finally the method is applied to deduce results on which the moment distribution method of analyzing rigid frames is based.