An extended Stein-type covariance identity for the Pearson family with applications to lower variance bounds

For an absolutely continuous (integer-valued) r.v. $X$ of the Pearson (Ord) family, we show that, under natural moment conditions, a Stein-type covariance identity of order $k$ holds (cf. [Goldstein and Reinert, J. Theoret. Probab. 18 (2005) 237--260]). This identity is closely related to the corresponding sequence of orthogonal polynomials, obtained by a Rodrigues-type formula, and provides convenient expressions for the Fourier coefficients of an arbitrary function. Application of the covariance identity yields some novel expressions for the corresponding lower variance bounds for a function of the r.v. $X$, expressions that seem to be known only in particular cases (for the Normal, see [Houdr\'{e} and Kagan, J. Theoret. Probab. 8 (1995) 23--30]; see also [Houdr\'{e} and P\'{e}rez-Abreu, Ann. Probab. 23 (1995) 400--419] for corresponding results related to the Wiener and Poisson processes). Some applications are also given.Comment: Published in at http://dx.doi.org/10.3150/10-BEJ282 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Another extension of the disc algebra

We identify the complex plane C with the open unit disc D={z:|z|<1} by the homeomorphism z --> z/(1+|z|). This leads to a compactification $\bar{C}$ of C, homeomorphic to the closed unit disc. The Euclidean metric on the closed unit disc induces a metric d on $\bar{C}$. We identify all uniform limits of polynomials on $\bar{D}$ with respect to the metric d. The class of the above limits is an extension of the disc algebra and it is denoted by $\bar{A}(D)$. We study properties of the elements of $\bar{A}(D)$ and topological properties of the class $\bar{A}(D)$ endowed with its natural topology. The class $\bar{A}(D)$ is different and, from the geometric point of view, richer than the class $\tilde{A}(D)$ introduced in Nestoridis (2010), Arxiv:1009.5364, on the basis of the chordal metric.Comment: 14 page

A Space Without Memory: Time and the Sublime in the Work of Janet Cardiff and George Bures Miller

The central question of my investigation is: how do artists present the unpresentable when presentation itself is impossible? Concentrating solely on Janet Cardiff and George Bures Miller’s artworks Opera For a Small Room (2005) and The Killing Machine (2007), I redevelop Jean François Lyotard’s concept of the sublime as put forth in his The Inhuman: Reflections on Time, in order to ask how Cardiff and Miller give shape to the unpresentable in their work. Opera and Killing are works that dynamically problematize and play with ideas of presentation, subjectivity, memory, and time. Thus, I explore my central question of presentation or present/presence outlined in my first chapter through three key themes: memory, time, and subjectivity, which correspond to chapters two, three, and four. I argue that Opera For a Small Room and The Killing Machine by Canadian installation artists Janet Cardiff and George Bures Miller answer this question of presentation by provoking us to experience the sensation of present/presence and enabling us to rethink the sublime as space without memory

Strengthened Chernoff-type variance bounds

Let $X$ be an absolutely continuous random variable from the integrated Pearson family and assume that $X$ has finite moments of any order. Using some properties of the associated orthonormal polynomial system, we provide a class of strengthened Chernoff-type variance bounds.Comment: Published in at http://dx.doi.org/10.3150/12-BEJ484 the Bernoulli (http://isi.cbs.nl/bernoulli/) by the International Statistical Institute/Bernoulli Society (http://isi.cbs.nl/BS/bshome.htm

Linear Estimation of Location and Scale Parameters Using Partial Maxima

Consider an i.i.d. sample X^*_1,X^*_2,...,X^*_n from a location-scale family, and assume that the only available observations consist of the partial maxima (or minima)sequence, X^*_{1:1},X^*_{2:2},...,X^*_{n:n}, where X^*_{j:j}=max{X^*_1,...,X^*_j}. This kind of truncation appears in several circumstances, including best performances in athletics events. In the case of partial maxima, the form of the BLUEs (best linear unbiased estimators) is quite similar to the form of the well-known Lloyd's (1952, Least-squares estimation of location and scale parameters using order statistics, Biometrika, vol. 39, pp. 88-95) BLUEs, based on (the sufficient sample of) order statistics, but, in contrast to the classical case, their consistency is no longer obvious. The present paper is mainly concerned with the scale parameter, showing that the variance of the partial maxima BLUE is at most of order O(1/log n), for a wide class of distributions.Comment: This article is devoted to the memory of my six-years-old, little daughter, Dionyssia, who leaved us on August 25, 2010, at Cephalonia isl. (26 pages, to appear in Metrika

MyChEMBL: A Virtual Platform for Distributing Cheminformatics Tools and Open Data

MyChEMBL is an open virtual platform which provides a free, secure, standardised and easy to use chemoinformatics environment for bioactivity data mining, machine learning, application development, learning and teaching. The main technical features of myChEMBL along with its applications and future plans are discussed here.FWN – Publicaties zonder aanstelling Universiteit Leide

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

A large-scale crop protection bioassay data set

Medicinal Chemistr

Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors

Background: Data suggest that immunomodulation induced by DNA hypomethylating agents can sensitize tumors to immune checkpoint inhibitors. We conducted a phase 1 dose-escalation trial (NCT02998567) of guadecitabine and pembrolizumab in patients with advanced solid tumors. We hypothesized that guadecitabine will overcome pembrolizumab resistance. Methods: Patients received guadecitabine (45 mg/m 2 or 30 mg/m 2, administered subcutaneously on days 1-4), with pembrolizumab (200 mg administered intravenously starting from cycle 2 onwards) every 3 weeks. Primary endpoints were safety, tolerability and maximum tolerated dose; secondary and exploratory endpoints included objective response rate (ORR), changes in methylome, transcriptome, immune contextures in pre-treatment and on-treatment tumor biopsies. Results: Between January 2017 and January 2020, 34 patients were enrolled. The recommended phase II dose was guadecitabine 30 mg/m 2, days 1-4, and pembrolizumab 200 mg on day 1 every 3 weeks. Two dose-limiting toxicities (neutropenia, febrile neutropenia) were reported at guadecitabine 45 mg/m 2 with none reported at guadecitabine 30 mg/m 2. The most common treatment-related adverse events (TRAEs) were neutropenia (58.8%), fatigue (17.6%), febrile neutropenia (11.8%) and nausea (11.8%). Common, grade 3+ TRAEs were neutropaenia (38.2%) and febrile neutropaenia (11.8%). There were no treatment-related deaths. Overall, 30 patients were evaluable for antitumor activity; ORR was 7% with 37% achieving disease control (progression-free survival) for ≥24 weeks. Of 12 evaluable patients with non-small cell lung cancer, 10 had been previously treated with immune checkpoint inhibitors with 5 (42%) having disease control ≥24 weeks (clinical benefit). Reduction in LINE-1 DNA methylation following treatment in blood (peripheral blood mononuclear cells) and tissue samples was demonstrated and methylation at transcriptional start site and 5' untranslated region gene regions showed enriched negative correlation with gene expression. Increases in intra-tumoural effector T-cells were seen in some responding patients. Patients having clinical benefit had high baseline inflammatory signature on RNAseq analyses. Conclusions: Guadecitabine in combination with pembrolizumab is tolerable with biological and anticancer activity. Reversal of previous resistance to immune checkpoint inhibitors is demonstrated