On the Complexity of Searching in Trees: Average-case Minimization

We focus on the average-case analysis: A function w : V -> Z+ is given which defines the likelihood for a node to be the one marked, and we want the strategy that minimizes the expected number of queries. Prior to this paper, very little was known about this natural question and the complexity of the problem had remained so far an open question. We close this question and prove that the above tree search problem is NP-complete even for the class of trees with diameter at most 4. This results in a complete characterization of the complexity of the problem with respect to the diameter size. In fact, for diameter not larger than 3 the problem can be shown to be polynomially solvable using a dynamic programming approach. In addition we prove that the problem is NP-complete even for the class of trees of maximum degree at most 16. To the best of our knowledge, the only known result in this direction is that the tree search problem is solvable in O(|V| log|V|) time for trees with degree at most 2 (paths). We match the above complexity results with a tight algorithmic analysis. We first show that a natural greedy algorithm attains a 2-approximation. Furthermore, for the bounded degree instances, we show that any optimal strategy (i.e., one that minimizes the expected number of queries) performs at most O(\Delta(T) (log |V| + log w(T))) queries in the worst case, where w(T) is the sum of the likelihoods of the nodes of T and \Delta(T) is the maximum degree of T. We combine this result with a non-trivial exponential time algorithm to provide an FPTAS for trees with bounded degree

Optimal constraint-based decision tree induction from itemset lattices

International audienceIn this article we show that there is a strong connection between decision tree learning and local pattern mining. This connection allows us to solve the computationally hard problem of finding optimal decision trees in a wide range of applications by post-processing a set of patterns: we use local patterns to construct a global model. We exploit the connection between constraints in pattern mining and constraints in decision tree induction to develop a framework for categorizing decision tree mining constraints. This framework allows us to determine which model constraints can be pushed deeply into the pattern mining process, and allows us to improve the state-of-the-art of optimal decision tree induction

<i>ABCB1</i> (MDR1) induction defines a common resistance mechanism in paclitaxel- and olaparib-resistant ovarian cancer cells

BACKGROUND: Clinical response to chemotherapy for ovarian cancer is frequently compromised by the development of drug-resistant disease. The underlying molecular mechanisms and implications for prescription of routinely prescribed chemotherapy drugs are poorly understood. METHODS: We created novel A2780-derived ovarian cancer cell lines resistant to paclitaxel and olaparib following continuous incremental drug selection. MTT assays were used to assess chemosensitivity to paclitaxel and olaparib in drug-sensitive and drug-resistant cells±the ABCB1 inhibitors verapamil and elacridar and cross-resistance to cisplatin, carboplatin, doxorubicin, rucaparib, veliparib and AZD2461. ABCB1 expression was assessed by qRT-PCR, copy number, western blotting and immunohistochemical analysis and ABCB1 activity assessed by the Vybrant and P-glycoprotein-Glo assays. RESULTS: Paclitaxel-resistant cells were cross-resistant to olaparib, doxorubicin and rucaparib but not to veliparib or AZD2461. Resistance correlated with increased ABCB1 expression and was reversible following treatment with the ABCB1 inhibitors verapamil and elacridar. Active efflux of paclitaxel, olaparib, doxorubicin and rucaparib was confirmed in drug-resistant cells and in ABCB1-expressing bacterial membranes. CONCLUSIONS: We describe a common ABCB1-mediated mechanism of paclitaxel and olaparib resistance in ovarian cancer cells. Optimal choice of PARP inhibitor may therefore limit the progression of drug-resistant disease, while routine prescription of first-line paclitaxel may significantly limit subsequent chemotherapy options in ovarian cancer patients

Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy

Exploring miniature insect brains using micro-CT scanning techniques

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Proactive and reactive accumulation-to-bound processes compete during perceptual decisions

Standard models of perceptual decision-making postulate that a response is triggered in reaction to stimulus presentation when the accumulated stimulus evidence reaches a decision threshold. This framework excludes however the possibility that informed responses are generated proactively at a time independent of stimulus. Here, we find that, in a free reaction time auditory task in rats, reactive and proactive responses coexist, suggesting that choice selection and motor initiation, commonly viewed as serial processes, are decoupled in general. We capture this behavior by a novel model in which proactive and reactive responses are triggered whenever either of two competing processes, respectively Action Initiation or Evidence Accumulation, reaches a bound. In both types of response, the choice is ultimately informed by the Evidence Accumulation process. The Action Initiation process readily explains premature responses, contributes to urgency effects at long reaction times and mediates the slowing of the responses as animals get satiated and tired during sessions. Moreover, it successfully predicts reaction time distributions when the stimulus was either delayed, advanced or omitted. Overall, these results fundamentally extend standard models of evidence accumulation in decision making by showing that proactive and reactive processes compete for the generation of responses

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications

Current and Emerging Radiotracers in Molecular Cardiovascular Imaging

Cardiovascular imaging has rapidly advanced over the past decades. Traditional imaging techniques such as echocardiography, computed tomography, and cardiovascular magnetic resonance are essential for assessing the structural and functional aspects of the cardiovascular system but often fall short in providing direct insights into disease activity. This gap is increasingly being bridged by molecular nuclear imaging techniques, including positron emission tomography and single-photon emission computed tomography, which enable the visualization of disease processes at the molecular and cellular levels. This review highlights the role of cardiovascular molecular imaging, emphasizing its current and potential applications in diagnosing and managing cardiovascular disease. With advancements in positron emission tomography scanners, novel radiotracers, and sophisticated imaging software, molecular imaging is set to play an essential role in precision medicine by enhancing our understanding of disease mechanisms, accelerating the development of targeted therapies, and facilitating personalized patient care.</p

Hot spot imaging in cardiovascular diseases:an information statement from SNMMI, ASNC, and EANM

This information statement from the Society of Nuclear Medicine and Molecular Imaging, American Society of Nuclear Cardiology, and European Association of Nuclear Medicine describes the performance, interpretation, and reporting of hot spot imaging in nuclear cardiology. The field of nuclear cardiology has historically focused on cold spot imaging for the interpretation of myocardial ischemia and infarction. Hot spot imaging has been an important part of nuclear medicine, particularly for oncology or infection indications, and the use of hot spot imaging in nuclear cardiology continues to expand. This document focuses on image acquisition and processing, methods of quantification, indications, protocols, and reporting of hot spot imaging. Indications discussed include myocardial viability, myocardial inflammation, device or valve infection, large vessel vasculitis, valve calcification and vulnerable plaques, and cardiac amyloidosis. This document contextualizes the foundations of image quantification and highlights reporting in each indication for the cardiac nuclear imager.</p