Grasp planning under uncertainty

The planning of dexterous grasps for multifingered robot hands operating in uncertain environments is covered. A sensor-based approach to the planning of a reach path prior to grasping is first described. An on-line, joint space finger path planning algorithm for the enclose phase of grasping was then developed. The algorithm minimizes the impact momentum of the hand. It uses a Preshape Jacobian matrix to map task-level hand preshape requirements into kinematic constraints. A master slave scheme avoids inter-finger collisions and reduces the dimensionality of the planning problem

Nonparametric Transient Classification using Adaptive Wavelets

Classifying transients based on multi band light curves is a challenging but crucial problem in the era of GAIA and LSST since the sheer volume of transients will make spectroscopic classification unfeasible. Here we present a nonparametric classifier that uses the transient's light curve measurements to predict its class given training data. It implements two novel components: the first is the use of the BAGIDIS wavelet methodology - a characterization of functional data using hierarchical wavelet coefficients. The second novelty is the introduction of a ranked probability classifier on the wavelet coefficients that handles both the heteroscedasticity of the data in addition to the potential non-representativity of the training set. The ranked classifier is simple and quick to implement while a major advantage of the BAGIDIS wavelets is that they are translation invariant, hence they do not need the light curves to be aligned to extract features. Further, BAGIDIS is nonparametric so it can be used for blind searches for new objects. We demonstrate the effectiveness of our ranked wavelet classifier against the well-tested Supernova Photometric Classification Challenge dataset in which the challenge is to correctly classify light curves as Type Ia or non-Ia supernovae. We train our ranked probability classifier on the spectroscopically-confirmed subsample (which is not representative) and show that it gives good results for all supernova with observed light curve timespans greater than 100 days (roughly 55% of the dataset). For such data, we obtain a Ia efficiency of 80.5% and a purity of 82.4% yielding a highly competitive score of 0.49 whilst implementing a truly "model-blind" approach to supernova classification. Consequently this approach may be particularly suitable for the classification of astronomical transients in the era of large synoptic sky surveys.Comment: 14 pages, 8 figures. Published in MNRA

K-ATP channel gene expression is induced by urocortin and mediates its cardioprotective effect

Background-Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion.Methods and Results-We have analyzed global changes in gone expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K-ATP channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia.Conclusions-This is, to our knowledge, the first report of the altered expression of a K-ATP. channel subunit induced by a cardioprotective agent and demonstrates that K-ATP, channel opening is essential for the effect of this novel cardioprotective agent

The usefulness of earnings and cash flows in valuing security returns: empirical evidence for the U.K, U.S.A and France.

In this dissertation, I proposed to examine and test empirically six major hypotheses that relate to the role of financial information, namely earnings and cash flows, in three major capital markets, two Anglo-Saxon, the UK and the USA and one code law country, France. A theoretical framework is developed to set the groundwork for building up my research hypotheses. I hypothesize that the homogeneity across firms may not hold, due to firm-specific, industry-specific, and country specific differences across firms. The dataset consists of 36,695 USA, 4,234 UK and 1,181 French firm-year observations over the period 1990-98. Multivariate statistical regression analysis is undertaken to test the major research hypotheses. The major conclusions drawn from the empirical results are summarized as follows. First, results indicate that indeed both earnings and cash flows are taken into consideration by investors in their investment decisions. Second, given cash flows, results show that earnings are always very important to investors and financial analysts for investment purposes; given earnings though results show that cash flows are more important to investors in the Anglo-Saxon countries, possibly due to the lower importance that investors place on the manipulated earnings in these less conservative countries. As far as France is concerned, results reveal that investors place much more attention to earnings and less attention to cash flows. Third, results show that the value relevance of earnings and cash flows is industry specific. Fourth, evidence shows that investors pay more attention to longer-run earnings and cash flows rather than to shorter-run financial information. Fifth, when earnings are transitory (not stable), investors pay more attention to cash flows and less attention to earnings, a result indicating that investors penalize firms with unstable earnings. Sixth, results show that the value relevance of earnings and cash flows is country specific. Specifically, results indicate that earnings are valued more in France and less in the Anglo-Saxon countries, due to the fact that the financial Saxon countries is much more liberal (less conservative) and managers may manipulate easier financial information. Moreover, as hypothesized, results show that cash flows are the most (least) value relevant in the USA and the UK (France). In summary, the evidence provided in this dissertation supports that indeed there are substantial differences in the way investors and financial analysts perceive financial information such as earnings and cash flows in the UK, France and the USA. The results of this dissertation should be of great importance to the major stakeholders such as investors, creditors, financial analysts, especially after the latest financial scandals and collapses of giant organizations worldwide. Furthermore, these results support that fundamental analysis does play a very important role in the capital markets and it should be taken more seriously into consideration by the stakeholders for investing, credit, financing and valuation analysis purposes

Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their value for detection of adenomas and adenocarcinomas

Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p<0.001), compared to non-malignant tissues, while methylation levels displayed the inverse pattern (p<0.001, p=0.001 and p=0.004 respectively). In colon cancer cell lines, overexpression of Uc160 and Uc346 led to increased proliferation and migration rates. Methylation levels of Uc160 in plasma of 50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis predicted the presence of CRC with 35% sensitivity and 89% specificity (p=0.016), while methylation levels of the combination of all three T-UCRs resulted in 45% sensitivity and 74.3% specificity (p=0.013). In conclusion, studied T-UCRs’ expression and methylation status are deregulated in CRC while Uc160 and Uc346 appear to have a complicated role in CRC progression. Moreover their methylation status appears a promising non-invasive screening test for CRC, provided that the sensitivity of the assay is improved

Quantifying chain reptation in entangled polymer melts: Topological and dynamical mapping of atomistic simulation results onto the tube model

The topological state of entangled polymers has been analyzed recently in terms of primitive paths which allowed obtaining reliable predictions of the static (statistical) properties of the underlying entanglement network for a number of polymer melts. Through a systematic methodology that first maps atomistic molecular dynamics (MD) trajectories onto time trajectories of primitive chains and then documents primitive chain motion in terms of a curvilinear diffusion in a tubelike region around the coarse-grained chain contour, we are extending these static approaches here even further by computing the most fundamental function of the reptation theory, namely, the probability ?? (s,t) that a segment s of the primitive chain remains inside the initial tube after time t, accounting directly for contour length fluctuations and constraint release. The effective diameter of the tube is independently evaluated by observing tube constraints either on atomistic displacements or on the displacement of primitive chain segments orthogonal to the initial primitive path. Having computed the tube diameter, the tube itself around each primitive path is constructed by visiting each entanglement strand along the primitive path one after the other and approximating it by the space of a small cylinder having the same axis as the entanglement strand itself and a diameter equal to the estimated effective tube diameter. Reptation of the primitive chain longitudinally inside the effective constraining tube as well as local transverse fluctuations of the chain driven mainly from constraint release and regeneration mechanisms are evident in the simulation results; the latter causes parts of the chains to venture outside their average tube surface for certain periods of time. The computed ?? (s,t) curves account directly for both of these phenomena, as well as for contour length fluctuations, since all of them are automatically captured in the atomistic simulations. Linear viscoelastic properties such as the zero shear rate viscosity and the spectra of storage and loss moduli obtained on the basis of the obtained ?? (s,t) curves for three different polymer melts (polyethylene, cis-1,4-polybutadiene, and trans-1,4-polybutadiene) are consistent with experimental rheological data and in qualitative agreement with the double reptation and dual constraint models. The new methodology is general and can be routinely applied to analyze primitive path dynamics and chain reptation in atomistic trajectories (accumulated through long MD simulations) of other model polymers or polymeric systems (e.g., bidisperse, branched, grafted, etc.); it is thus believed to be particularly useful in the future in evaluating proposed tube models and developing more accurate theories for entangled systems.open342

Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface

Plasma concentrations of biologically active vitamin D (1,25- (OH)2D) are tightly controlled via feedback regulation of renal 1-hydroxylase (CYP27B1; positive) and 24-hydroxylase (CYP24A1; catabolic) enzymes. In pregnancy, this regulation is uncoupled, and 1,25-(OH)2D levels are significantly elevated, suggesting a role in pregnancy progression. Epigenetic regulation of CYP27B1 and CYP24A1 has previously been described in cell and animal models, and despite emerging evidence for a critical role of epigenetics in placentation generally, little is known about the regulation of enzymes modulating vitamin D homeostasis at the fetomaternal interface. In this study, we investigated the methylation status of genes regulating vitamin D bioavailability and activity in the placenta. No methylation of the VDR (vitamin D receptor) and CYP27B1 genes was found in any placental tissues. In contrast, the CYP24A1 gene is methylated in human placenta, purified cytotrophoblasts, and primary and cultured chorionic villus sampling tissue. No methylation was detected in any somatic human tissue tested. Methylation was also evident in marmoset and mouse placental tissue. All three genes were hypermethylated in choriocarcinoma cell lines, highlighting the role of vitaminDderegulation in this cancer. Gene expression analysis confirmed a reduced capacity for CYP24A1 induction with promoter methylation in primary cells and in vitro reporter analysis demonstrated that promoter methylation directly down-regulates basal promoter activity and abolishes vitamin D-mediated feedback activation. This study strongly suggests that epigenetic decoupling of vitamin D feedback catabolism plays an important role in maximizing active vitamin D bioavailability at the fetomaternal interface

Permutation invariant Gaussian matrix models for financial correlation matrices

We construct an ensemble of correlation matrices from high-frequency foreign exchange market data, with one matrix for every day for 446 days. The matrices are symmetric and have vanishing diagonal elements after subtracting the identity matrix. For such ensembles, we construct the general permutation invariant Gaussian matrix model, which has 4 parameters characterised using the representation theory of symmetric groups. The permutation invariant polynomial functions of the symmetric, diagonally vanishing matrices have a basis labelled by undirected loop-less graphs. Using the expectation values of the general linear and quadratic permutation invariant functions of the matrices in the dataset, the 4 parameters of the matrix model are determined. The model then predicts the expectation values of the cubic and quartic polynomials. These predictions are compared to the data to give strong evidence for a good overall fit of the permutation invariant Gaussian matrix model. The linear, quadratic, cubic and quartic polynomial functions are then used to define low-dimensional feature vectors for the days associated to the matrices. These vectors, with choices informed by the refined structure of small non-Gaussianities, are found to be effective as a tool for anomaly detection in market states: statistically significant correlations are established between atypical days as defined using these feature vectors, and days with significant economic events as recognized in standard foreign exchange economic calendars. They are also shown to be useful as a tool for ranking pairs of days in terms of their similarity, yielding a strongly statistically significant correlation with a ranking based on a higher dimensional proxy for visual similarity

Rapid and Sensitive Assessment of Globin Chains for Gene and Cell Therapy of Hemoglobinopathies

The β-hemoglobinopathies sickle cell anemia and β-thalassemia are the focus of many gene-therapy studies. A key disease parameter is the abundance of globin chains because it indicates the level of anemia, likely toxicity of excess or aberrant globins, and therapeutic potential of induced or exogenous β-like globins. Reversed-phase high-performance liquid chromatography (HPLC) allows versatile and inexpensive globin quantification, but commonly applied protocols suffer from long run times, high sample requirements, or inability to separate murine from human β-globin chains. The latter point is problematic for in vivo studies with gene-addition vectors in murine disease models and mouse/human chimeras. This study demonstrates HPLC-based measurements of globin expression (1) after differentiation of the commonly applied human umbilical cord blood-derived erythroid progenitor-2 cell line, (2) in erythroid progeny of CD34+ cells for the analysis of clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of the globin regulator BCL11A, and (3) of transgenic mice holding the human β-globin locus. At run times of 8 min for separation of murine and human β-globin chains as well as of human γ-globin chains, and with routine measurement of globin-chain ratios for 12 nL of blood (tested for down to 0.75 nL) or of 300,000 in vitro differentiated cells, the methods presented here and any variant-specific adaptations thereof will greatly facilitate evaluation of novel therapy applications for β-hemoglobinopathies

Measurement of lentiviral vector titre and copy number by cross-species duplex quantitative PCR

Lentiviruses are the vectors of choice for many preclinical studies and clinical applications of gene therapy. Accurate measurement of biological vector titre before treatment is a prerequisite for vector dosing, and the calculation of vector integration sites per cell after treatment is as critical to the characterisation of modified cell products as it is to long-term follow-up and the assessment of risk and therapeutic efficiency in patients. These analyses are typically based on quantitative real-time PCR (qPCR), but as yet compromise accuracy and comparability between laboratories and experimental systems, the former by using separate simplex reactions for the detection of endogene and lentiviral sequences and the latter by designing different PCR assays for analyses in human cells and animal disease models. In this study, we validate in human and murine cells a qPCR system for the single-tube assessment of lentiviral vector copy numbers that is suitable for analyses in at least 33 different mammalian species, including human and other primates, mouse, pig, cat and domestic ruminants. The established assay combines the accuracy of single-tube quantitation by duplex qPCR with the convenience of one-off assay optimisation for cross-species analyses and with the direct comparability of lentiviral transduction efficiencies in different species.</p