Molecular evidence for the clonal origin of blast crisis in chronic myeloid leukaemia.

Cytogenetic and enzymatic studies have shown that chronic myeloid leukemia (CML) represents the clonal proliferation of a pluripotent stem cell. The Philadelphia chromosome (Ph') is the characteristic karyotypic abnormality seen in this disease, although the exact role of this clonal marker in the pathogenesis of CML is uncertain. At a molecular level, the Ph' has recently been shown to represent the translocation of c-abl to a limited (breakpoint cluster region, bcr) on chromosome 22. We have used probes for the bcr gene to obtain molecular evidence for the clonal origin of blast crisis in 2 patient with CML. In both cases, the first with myeloid and the second with lymphoid blast crisis, there was rearrangement of the bcr gene. The patterns of rearrangement varied between patients but were identical when comparing acute and chronic phases within the same individual. As the Ph' translocation is thought to represent a random recombination event these data not only provide further evidence for the clonal origin of blast crisis in CML, but also suggest that in the second patient this translocation event had already occurred at the pluripotent stem cell

Emergence of fractal behavior in condensation-driven aggregation

We investigate a model in which an ensemble of chemically identical Brownian particles are continuously growing by condensation and at the same time undergo irreversible aggregation whenever two particles come into contact upon collision. We solved the model exactly by using scaling theory for the case whereby a particle, say of size $x$, grows by an amount $\alpha x$ over the time it takes to collide with another particle of any size. It is shown that the particle size spectra of such system exhibit transition to dynamic scaling $c(x,t)\sim t^{-\beta}\phi(x/t^z)$ accompanied by the emergence of fractal of dimension $d_f={{1}\over{1+2\alpha}}$. One of the remarkable feature of this model is that it is governed by a non-trivial conservation law, namely, the $d_f^{th}$ moment of $c(x,t)$ is time invariant regardless of the choice of the initial conditions. The reason why it remains conserved is explained by using a simple dimensional analysis. We show that the scaling exponents $\beta$ and $z$ are locked with the fractal dimension $d_f$ via a generalized scaling relation $\beta=(1+d_f)z$.Comment: 8 pages, 6 figures, to appear in Phys. Rev.

Support varieties for selfinjective algebras

Support varieties for any finite dimensional algebra over a field were introduced by Snashall-Solberg using graded subalgebras of the Hochschild cohomology. We mainly study these varieties for selfinjective algebras under appropriate finite generation hypotheses. Then many of the standard results from the theory of support varieties for finite groups generalize to this situation. In particular, the complexity of the module equals the dimension of its corresponding variety, all closed homogeneous varieties occur as the variety of some module, the variety of an indecomposable module is connected, periodic modules are lines and for symmetric algebras a generalization of Webb's theorem is true

A family of diameter-based eigenvalue bounds for quantum graphs

We establish a sharp lower bound on the first non-trivial eigenvalue of the Laplacian on a metric graph equipped with natural (i.e., continuity and Kirchhoff) vertex conditions in terms of the diameter and the total length of the graph. This extends a result of, and resolves an open problem from, [J. B. Kennedy, P. Kurasov, G. Malenov\'a and D. Mugnolo, Ann. Henri Poincar\'e 17 (2016), 2439--2473, Section 7.2], and also complements an analogous lower bound for the corresponding eigenvalue of the combinatorial Laplacian on a discrete graph. We also give a family of corresponding lower bounds for the higher eigenvalues under the assumption that the total length of the graph is sufficiently large compared with its diameter. These inequalities are sharp in the case of trees.Comment: Substantial revision of v1. The main result, originally for the first eigenvalue, has been generalised to the higher ones. The title has been changed and the proofs substantially reorganised to reflect the new result, and a section containing concluding remarks has been adde

Concordance of Illness Representations: The Key to Improving Care of Medically Unexplained Symptoms

How can effective patient-provider relationships be developed when the underlying cause of the health condition is not well understood and becomes a point of controversy between patient and provider? This problem underlies the difficulty in treating medically unexplained symptoms and syndromes (MUS; e.g., fibromyalgia, chronic fatigue syndrome), which primary care providers consider to be among the most difficult conditions to treat.1 This difficulty extends to the patient-provider relationship which is characterized by discord over MUS.1 In this article, we argue that the key to improving the patient provider relationship is for the patient and provider to develop congruent illness perceptions about MUS

Spectral simplicity and asymptotic separation of variables

We describe a method for comparing the real analytic eigenbranches of two families of quadratic forms that degenerate as t tends to zero. One of the families is assumed to be amenable to `separation of variables' and the other one not. With certain additional assumptions, we show that if the families are asymptotic at first order as t tends to 0, then the generic spectral simplicity of the separable family implies that the eigenbranches of the second family are also generically one-dimensional. As an application, we prove that for the generic triangle (simplex) in Euclidean space (constant curvature space form) each eigenspace of the Laplacian is one-dimensional. We also show that for all but countably many t, the geodesic triangle in the hyperbolic plane with interior angles 0, t, and t, has simple spectrum.Comment: 53 pages, 2 figure

Second-order gravitational self-force

We derive an expression for the second-order gravitational self-force that acts on a self-gravitating compact-object moving in a curved background spacetime. First we develop a new method of derivation and apply it to the derivation of the first-order gravitational self-force. Here we find that our result conforms with the previously derived expression. Next we generalize our method and derive a new expression for the second-order gravitational self-force. This study also has a practical motivation: The data analysis for the planned gravitational wave detector LISA requires construction of waveforms templates for the expected gravitational waves. Calculation of the two leading orders of the gravitational self-force will enable one to construct highly accurate waveform templates, which are needed for the data analysis of gravitational-waves that are emitted from extreme mass-ratio binaries.Comment: 35 page

Inexact restoration method for derivative-free optimization with smooth constraints

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A new method is introduced for solving constrained optimization problems in which the derivatives of the constraints are available but the derivatives of the objective function are not. The method is based on the inexact restoration framework, by means of which each iteration is divided in two phases. In the first phase one considers only the constraints, in order to improve feasibility. In the second phase one minimizes a suitable objective function subject to a linear approximation of the constraints. The second phase must be solved using derivative-free methods. An algorithm introduced recently by Kolda, Lewis, and Torczon for linearly constrained derivative-free optimization is employed for this purpose. Under usual assumptions, convergence to stationary points is proved. A computer implementation is described and numerical experiments are presented.A new method is introduced for solving constrained optimization problems in which the derivatives of the constraints are available but the derivatives of the objective function are not. The method is based on the inexact restoration framework, by means of23211891213CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPERJ - FUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIROFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CNPq [E-26/171.164/2003-APQ1]FAPESP [FAPESP 2011-51305-0]FAPESP [03/09169-6, 06/53768-0, 07/06663-0, 08/00468-4]E-26/171.164/2003–APQ12011-51305-0; 03/09169-6; 06/53768-0; 07/06663-0; 08/00468-4sem informaçãoWe are indebted to associate editor Prof. Margaret Wright and two anonymous referees for many useful comments and remarks that led to significant improvement of this pape

Influence of primary particle density in the morphology of agglomerates

Agglomeration processes occur in many different realms of science such as colloid and aerosol formation or formation of bacterial colonies. We study the influence of primary particle density in agglomerate structure using diffusion-controlled Monte Carlo simulations with realistic space scales through different regimes (DLA and DLCA). The equivalence of Monte Carlo time steps to real time scales is given by Hirsch's hydrodynamical theory of Brownian motion. Agglomerate behavior at different time stages of the simulations suggests that three indices (fractal exponent, coordination number and eccentricity index) characterize agglomerate geometry. Using these indices, we have found that the initial density of primary particles greatly influences the final structure of the agglomerate as observed in recent experimental works.Comment: 11 pages, 13 figures, PRE, to appea