Closed form summation of C-finite sequences

We consider sums of the form $$\sum_{j=0}^{n-1}F_1(a_1n+b_1j+c_1)F_2(a_2n+b_2j+c_2)... F_k(a_kn+b_kj+c_k),$$ in which each $\{F_i(n)\}$ is a sequence that satisfies a linear recurrence of degree $D(i)<\infty$, with constant coefficients. We assume further that the $a_i$'s and the $a_i+b_i$'s are all nonnegative integers. We prove that such a sum always has a closed form, in the sense that it evaluates to a linear combination of a finite set of monomials in the values of the sequences $\{F_i(n)\}$ with coefficients that are polynomials in $n$. We explicitly describe two different sets of monomials that will form such a linear combination, and give an algorithm for finding these closed forms, thereby completely automating the solution of this class of summation problems. We exhibit tools for determining when these explicit evaluations are unique of their type, and prove that in a number of interesting cases they are indeed unique. We also discuss some special features of the case of ``indefinite summation," in which $a_1=a_2=... = a_k = 0$

An Online Decision-Theoretic Pipeline for Responder Dispatch

The problem of dispatching emergency responders to service traffic accidents, fire, distress calls and crimes plagues urban areas across the globe. While such problems have been extensively looked at, most approaches are offline. Such methodologies fail to capture the dynamically changing environments under which critical emergency response occurs, and therefore, fail to be implemented in practice. Any holistic approach towards creating a pipeline for effective emergency response must also look at other challenges that it subsumes - predicting when and where incidents happen and understanding the changing environmental dynamics. We describe a system that collectively deals with all these problems in an online manner, meaning that the models get updated with streaming data sources. We highlight why such an approach is crucial to the effectiveness of emergency response, and present an algorithmic framework that can compute promising actions for a given decision-theoretic model for responder dispatch. We argue that carefully crafted heuristic measures can balance the trade-off between computational time and the quality of solutions achieved and highlight why such an approach is more scalable and tractable than traditional approaches. We also present an online mechanism for incident prediction, as well as an approach based on recurrent neural networks for learning and predicting environmental features that affect responder dispatch. We compare our methodology with prior state-of-the-art and existing dispatch strategies in the field, which show that our approach results in a reduction in response time with a drastic reduction in computational time.Comment: Appeared in ICCPS 201

HLA class I and II genotype of the NCI-60 cell lines

Sixty cancer cell lines have been extensively characterized and used by the National Cancer Institute's Developmental Therapeutics Program (NCI-60) since the early 90's as screening tools for anti-cancer drug development. An extensive database has been accumulated that could be used to select individual cells lines for specific experimental designs based on their global genetic and biological profile. However, information on the human leukocyte antigen (HLA) genotype of these cell lines is scant and mostly antiquated since it was derived from serological typing. We, therefore, re-typed the NCI-60 panel of cell lines by high-resolution sequence-based typing. This information may be used to: 1) identify and verify the identity of the same cell lines at various institutions; 2) check for possible contaminant cell lines in culture; 3) adopt individual cell lines for experiments in which knowledge of HLA molecule expression is relevant. Since genome-based typing does not guarantee actual surface protein expression, further characterization of relevant cell lines should be entertained to verify surface expression in experiments requiring correct antigen presentation

The importance of RT-qPCR primer design for the detection of siRNA-mediated mRNA silencing

<p>Abstract</p> <p>Background</p> <p>The use of RNAi to analyse gene function <it>in vitro </it>is now widely applied in biological research. However, several difficulties are associated with its use <it>in vivo</it>, mainly relating to inefficient delivery and non-specific effects of short RNA duplexes in animal models. The latter can lead to false positive results when real-time RT-qPCR alone is used to measure target mRNA knockdown.</p> <p>Findings</p> <p>We observed that detection of an apparent siRNA-mediated knockdown <it>in vivo </it>was dependent on the primers used for real-time RT-qPCR measurement of the target mRNA. Two siRNAs specific for <it>RRM1 </it>with equivalent activity <it>in vitro </it>were administered to A549 xenografts via intratumoural injection. In each case, apparent knockdown of <it>RRM1 </it>mRNA was observed only when the primer pair used in RT-qPCR flanked the siRNA cleavage site. This false-positive result was found to result from co-purified siRNA interfering with both reverse transcription and qPCR.</p> <p>Conclusions</p> <p>Our data suggest that using primers flanking the siRNA-mediated cleavage site in RT-qPCR-based measurements of mRNA knockdown <it>in vivo </it>can lead to false positive results. This is particularly relevant where high concentrations of siRNA are introduced, particularly via intratumoural injection, as the siRNA may be co-purified with the RNA and interfere with downstream enzymatic steps. Based on these results, using primers flanking the siRNA target site should be avoided when measuring knockdown of target mRNA by real-time RT-qPCR.</p

The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function.

RATIONALE: Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer's disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned 'target' and 'non-target' stimuli at a single location. OBJECTIVES: The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer. METHODS: C57BL/6J, DBA/2J and CD1 mice (n = 15-16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0-3 mg/kg, i.p.). RESULTS: C57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d') across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks. CONCLUSIONS: rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.Funding for this research was provided by Professor Mark Johnson, Imperial College London. CHK received funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI11C1183). MHE, SRON, TWR, LMS, TJB and ACM received funding from the Innovative Medicine Initiative Joint Undertaking under grant agreement no 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). LMS and TJB were funded by Medical Research Council/Wellcome Trust grant 089703/Z/09/Z.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00213-015-4081-

Dysregulation of DAF-16/FOXO3A-mediated stress responses accelerates T oxidative DNA damage induced aging

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms displayed early activation of DAF-16 relative to wild-type worms, which conferred resistance to multiple stressors and was important for maximal longevity of the mutant worms. However, DAF- 16 activity was not maintained over the lifespan of ercc-1 animals and this decline in DAF-16 activation cor- responded with a loss of stress resistance, a rise in oxidant levels and increased morbidity, all of which were cep- 1/ p53 dependent. A similar early activation of FOXO3A (the mammalian homolog of DAF-16), with increased resistance to oxidative stress, followed by a decline in FOXO3A activity and an increase in oxidant abundance was observed in Ercc1-/- primary mouse embryonic fibroblasts. Likewise, in vivo, ERCC1-deficient mice had transient activation of FOXO3A in early adulthood as did middle-aged wild-type mice, followed by a late life decline. The healthspan and mean lifespan of ERCC1 deficient mice was rescued by inactivation of p53. These data indicate that activation of DAF-16/FOXO3A is a highly conserved response to genotoxic stress that is important for suppressing consequent oxidative stress. Correspondingly, dysregulation of DAF-16/FOXO3A appears to underpin shortened healthspan and lifespan, rather than the increased DNA damage burden itself