Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

Qubit state detection using the quantum Duffing oscillator

We introduce a detection scheme for the state of a qubit, which is based on resonant few-photon transitions in a driven nonlinear resonator. The latter is parametrically coupled to the qubit and is used as its detector. Close to the fundamental resonator frequency, the nonlinear resonator shows sharp resonant few-photon transitions. Depending on the qubit state, these few-photon resonances are shifted to different driving frequencies. We show that this detection scheme offers the advantage of small back action, a large discrimination power with an enhanced read-out fidelity, and a sufficiently large measurement efficiency. A realization of this scheme in the form of a persistent current qubit inductively coupled to a driven SQUID detector in its nonlinear regime is discussed.Comment: 10 pages, 6 figures. To appear in Phys. Rev.

The Caveolin-1 Connection to Cell Death and Survival

Nunez, S (Nunez, S.)[ 1,4 ] 1. Fac Med, CEMC, Lab Comunicac Celulares, Santiago, Chile. 4. Univ Talca, Fac Hlth Sci, Talca, ChileCaveolins are a family of membrane proteins required for the formation of small plasma membrane invaginations called caveolae that are implicated in cellular trafficking processes. In addition to this structural role, these scaffolding proteins modulate numerous intracellular signaling pathways; often via direct interaction with specific binding partners. Caveolin-1 is particularly well-studied in this respect and has been attributed a large variety of functions. Thus, Caveolin-1 also represents the best-characterized isoform of this family with respect to its participation in cancer. Rather strikingly, available evidence indicates that Caveolin-1 belongs to a select group of proteins that function, depending on the cellular settings, both as tumor suppressor and promoter of cellular traits commonly associated with enhanced malignant behavior, such as metastasis and multi-drug resistance. The mechanisms underlying such ambiguity in Caveolin-1 function constitute an area of great interest. Here, we will focus on discussing how Caveolin-1 modulates cell death and survival pathways and how this may contribute to a better understanding of the ambiguous role this protein plays in cancer

Parallelisation and application of AD3 as a method for solving large scale combinatorial auctions

Auctions, and combinatorial auctions (CAs), have been successfully employed to solve coordination problems in a wide range of application domains. However, the scale of CAs that can be optimally solved is small because of the complexity of the winner determination problem (WDP), namely of finding the bids that maximise the auctioneer’s revenue. A way of approximating the solution of a WDP is to solve its linear programming relaxation. The recently proposed Alternate Direction Dual Decomposition algorithm (AD3) has been shown to ef- ficiently solve large-scale LP relaxations. Hence, in this paper we show how to encode the WDP so that it can be approximated by means of AD3. Moreover, we present PAR-AD3, the first parallel implementation of AD3. PAR-AD3 shows to be up to 12.4 times faster than CPLEX in a single-thread execution, and up to 23 times faster than parallel CPLEX in an 8-core architecture. Therefore PAR- AD3 becomes the algorithm of choice to solve large-scale WDP LP relaxations for hard instances. Furthermore, PAR-AD3 has potential when considering large- scale coordination problems that must be solved as optimisation problems.Research supported by MICINN projects TIN2011-28689-C02-01, TIN2013-45732-C4-4-P and TIN2012-38876-C02-01Peer reviewe

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Quantum algorithm and circuit design solving the Poisson equation

The Poisson equation occurs in many areas of science and engineering. Here we focus on its numerical solution for an equation in d dimensions. In particular we present a quantum algorithm and a scalable quantum circuit design which approximates the solution of the Poisson equation on a grid with error \varepsilon. We assume we are given a supersposition of function evaluations of the right hand side of the Poisson equation. The algorithm produces a quantum state encoding the solution. The number of quantum operations and the number of qubits used by the circuit is almost linear in d and polylog in \varepsilon^{-1}. We present quantum circuit modules together with performance guarantees which can be also used for other problems.Comment: 30 pages, 9 figures. This is the revised version for publication in New Journal of Physic

Características y consecuencias de las agresiones sexuales en adolescentes consultantes en un centro de salud sexual y reproductiva

Antecedentes: La agresión sexual es un evento traumático y doloroso que afecta de manera transversal, a las víctimas de ambos sexos, de todos los niveles socioeconómicos con graves consecuencias para la salud física, psicológica y social para quienes la sufren. Objetivo: Determinar las características de las agresiones sexuales y sus consecuencias en adolescentes consultantes en un centro de atención en Salud Sexual y Reproductiva. Método: Estudio analítico de corte transversal de 573 adolescentes atendidas en un centro de medicina reproductiva (CEMERA) en el período 2003-2010 y que reportaron antecedente de abuso sexual. Se estudiaron tanto las características como las consecuencias del abuso, datos que se obtuvieron desde las fichas clínicas. Resultados: En el 86,5 % de los casos se reportó abuso sexual y en un 13,5% violación. El 48,5% de los agresores son familiares. La edad más vulnerable fue entre 5-9 años con un 41,2%. En el 39,2% el abuso sexual fue reiterado. En un 43,4% el lugar fue el propio hogar de la víctima. Un 70% reveló y de estos el 45,9% lo hizo en forma tardía. Sólo en un 19% se hizo la denuncia legal. De las adolescentes que iniciaron actividad sexual voluntaria (83,3%), un 35,4% tenía menos de 15 años. Un 11,8% reportó 3 y más parejas sexuales. Conclusión: El antecedente de abuso sexual debe ser considerado en la atención de adolescentes que consultan por salud sexual y reproductiva. El equipo de salud debe estar preparado para atender sus múltiples necesidades

An affinity matured minibody for PET imaging of prostate stem cell antigen (PSCA)-expressing tumors

PurposeProstate stem cell antigen (PSCA), a cell surface glycoprotein expressed in normal human prostate and bladder, is over-expressed in the majority of localized prostate cancer and most bone metastases. We have previously shown that the hu1G8 minibody, a humanized anti-PSCA antibody fragment (single-chain Fv-C(H)3 dimer, 80 kDa), can localize specifically and image PSCA-expressing xenografts at 21 h post-injection. However, the humanization and antibody fragment reformatting decreased its apparent affinity. Here, we sought to evaluate PET imaging contrast with affinity matured minibodies.MethodsYeast scFv display, involving four rounds of selection, was used to generate the three affinity matured antibody fragments (A2, A11, and C5) that were reformatted into minibodies. These three affinity matured anti-PSCA minibodies were characterized in vitro, and following radiolabeling with (124)I were evaluated in vivo for microPET imaging of PSCA-expressing tumors.ResultsThe A2, A11, and C5 minibody variants all demonstrated improved affinity compared to the parental (P) minibody and were ranked as follows: A2 > A11 > C5 > P. The (124)I-labeled A11 minibody demonstrated higher immunoreactivity than the parental minibody and also achieved the best microPET imaging contrast in two xenograft models, LAPC-9 (prostate cancer) and Capan-1 (pancreatic cancer), when evaluated in vivo.ConclusionOf the affinity variant minibodies tested, the A11 minibody that ranked second in affinity was selected as the best immunoPET tracer to image PSCA-expressing xenografts. This candidate is currently under development for evaluation in a pilot clinical imaging study