Parameterized Approximation Schemes using Graph Widths

Combining the techniques of approximation algorithms and parameterized complexity has long been considered a promising research area, but relatively few results are currently known. In this paper we study the parameterized approximability of a number of problems which are known to be hard to solve exactly when parameterized by treewidth or clique-width. Our main contribution is to present a natural randomized rounding technique that extends well-known ideas and can be used for both of these widths. Applying this very generic technique we obtain approximation schemes for a number of problems, evading both polynomial-time inapproximability and parameterized intractability bounds

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

Simple Summary Neuroblastoma is one of the most diffuse and the deadliest cancer in children. While many advances have been made in the last few decades to improve patients' outcome, high-risk neuroblastoma (HR-NB) still shows a very aggressive pattern of development and poor prognosis, with only a 50% chance of 5-year survival. Moreover, while many factors contribute to defining the high-risk condition, MYCN status is well established as the major element in pathology disclosure. The aim of this review is to describe the current knowledge in the diagnosis, prognosis and therapeutic approaches of HR-NB, particularly in relation to MYCN. The review highlights how MYCN influences the HR-NB scenario and the new therapeutic approaches that are currently proposed to target it, in consideration of MYCN as a highly relevant target for HR-NB patient management. Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high toxicity remain a staple feature of current high-risk neuroblastoma treatment. For this reason, more specific procedures are required, and new therapeutic targets are also needed for a precise medicine approach. In this scenario, MYCN is certainly one of the most interesting targets. Indeed, MYCN is one of the most relevant hallmarks of HR-NB, and many studies has been carried out in recent years to discover potent and specific inhibitors to block its activities and any related oncogenic function. N-Myc protein has been considered an undruggable target for a long time. Thus, many new indirect and direct approaches have been discovered and preclinically evaluated for the interaction with MYCN and its pathways; a few of the most promising approaches are nearing clinical application for the investigation in HR-NB

Are there any good digraph width measures?

Several different measures for digraph width have appeared in the last few years. However, none of them shares all the "nice" properties of treewidth: First, being \emph{algorithmically useful} i.e. admitting polynomial-time algorithms for all \MS1-definable problems on digraphs of bounded width. And, second, having nice \emph{structural properties} i.e. being monotone under taking subdigraphs and some form of arc contractions. As for the former, (undirected) \MS1 seems to be the least common denominator of all reasonably expressive logical languages on digraphs that can speak about the edge/arc relation on the vertex set.The latter property is a necessary condition for a width measure to be characterizable by some version of the cops-and-robber game characterizing the ordinary treewidth. Our main result is that \emph{any reasonable} algorithmically useful and structurally nice digraph measure cannot be substantially different from the treewidth of the underlying undirected graph. Moreover, we introduce \emph{directed topological minors} and argue that they are the weakest useful notion of minors for digraphs

Structurally Parameterized d-Scattered Set

In $d$-Scattered Set we are given an (edge-weighted) graph and are asked to select at least $k$ vertices, so that the distance between any pair is at least $d$, thus generalizing Independent Set. We provide upper and lower bounds on the complexity of this problem with respect to various standard graph parameters. In particular, we show the following: - For any $d\ge2$, an $O^*(d^{\textrm{tw}})$-time algorithm, where $\textrm{tw}$ is the treewidth of the input graph. - A tight SETH-based lower bound matching this algorithm's performance. These generalize known results for Independent Set. - $d$-Scattered Set is W[1]-hard parameterized by vertex cover (for edge-weighted graphs), or feedback vertex set (for unweighted graphs), even if $k$ is an additional parameter. - A single-exponential algorithm parameterized by vertex cover for unweighted graphs, complementing the above-mentioned hardness. - A $2^{O(\textrm{td}^2)}$-time algorithm parameterized by tree-depth ($\textrm{td}$), as well as a matching ETH-based lower bound, both for unweighted graphs. We complement these mostly negative results by providing an FPT approximation scheme parameterized by treewidth. In particular, we give an algorithm which, for any error parameter $\epsilon > 0$, runs in time $O^*((\textrm{tw}/\epsilon)^{O(\textrm{tw})})$ and returns a $d/(1+\epsilon)$-scattered set of size $k$, if a $d$-scattered set of the same size exists

Plasma Physics

Contains reports on seven research projects.United States Atomic Energy Commission under Contract AT(30-1)-1842Joint Services Electronics Programs (U.S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E

Neutron scattering study of PbMg1/3_{1/3}Ta2/3_{2/3}O3_3 and BaMg1/3_{1/3}Ta2/3_{2/3}O3_3 complex perovskites

Neutron scattering investigations were carried out in PbMg$_{1/3}$Ta$_{2/3}$O$_3$ and BaMg$_{1/3}$Ta$_{2/3}$O$_3$ complex perovskites. The crystal structure of both compounds does not show any phase transition in the temperature range 1.5 -- 730 K. Whereas the temperature dependence of the lattice parameter of BaMg$_{1/3}$Ta$_{2/3}$O$_3$ follows the classical expectations, the lattice parameter of relaxor ferroelectric PbMg$_{1/3}$Ta$_{2/3}$O$_3$ exhibits anomalies. One of these anomalies is observed in the same temperature range as the peak in the dielectric susceptibility. We find that in PbMg$_{1/3}$Ta$_{2/3}$O$_3$, lead ions are displaced from the ideal positions in the perovskite structure at all temperatures. Consequently short-range order is present. This induces strong diffuse scattering with an anisotropic shape in wavevector space. The temperature dependences of the diffuse neutron scattering intensity and of the amplitude of the lead displacements are similar

Evidence for MBM_B and MCM_C phases in the morphotropic phase boundary region of (1−x)[Pb(Mg1/3Nb2/3)O3]−xPbTiO3(1-x)[Pb(Mg_{1/3}Nb_{2/3})O_3]-xPbTiO_3 : A Rietveld study

We present here the results of the room temperature dielectric constant measurements and Rietveld analysis of the powder x-ray diffraction data on $(1-x)[Pb(Mg_{1/3}Nb_{2/3})O_3]-xPbTiO_3$(PMN-$x$PT) in the composition range $0.20 \leq x \leq 0.45$ to show that the morphotropic phase boundary (MPB) region contains two monoclinic phases with space groups Cm (or $M_B$ type) and Pm (or $M_C$ type) stable in the composition ranges $0.27 \leq x \leq 0.30$ and $0.31 \leq x \leq 0.34$, respectively. The structure of PMN-$x$PT in the composition ranges $0 \leq x \leq$ 0.26, and $0.35 \leq x \leq1$ is found to be rhombohedral (R3m) and tetragonal (P4mm), respectively. These results are compared with the predictions of Vanderbilt & Cohen's theory.Comment: 20 pages, 11 pdf figure

10 ps timing with highly irradiated 3D trench silicon pixel sensors

In this paper the results of a beam test characterization campaign of 3D trench silicon pixel sensors are presented. A time resolution in the order of 10 ps was measured both for non-irradiated and irradiated sensors up to a fluence of $2.5 \cdot 10^{16}\,1\,MeV\, n_{eq}\,cm^{-2}$. This feature and a detection efficiency close to $99\%$ make this sensors one of the best candidates for 4D tracking detectors in High-Energy-Physics experiments.Comment: Prepared for submission to JINST, IWORID 202

Effect of pathologic tumor response and nodal status on survival in the medical research council adjuvant gastric infusional chemotherapy trial

Purpose: The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable esophagogastric cancer. However, identification of patients at risk for relapse remains challenging. We evaluated whether pathologic response and lymph node status after neoadjuvant chemotherapy are prognostic in patients treated in the MAGIC trial. Materials and Methods: Pathologic regression was assessed in resection specimens by two independent pathologists using the Mandard tumor regression grading system (TRG). Differences in overall survival (OS) according to TRG were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards method established the relationships among TRG, clinical-pathologic variables, and OS. Results: Three hundred thirty resection specimens were analyzed. In chemotherapy-treated patients with a TRG of 1 or 2, median OS was not reached, whereas for patients with a TRG of 3, 4, or 5, median OS was 20.47 months. On univariate analysis, high TRG and lymph node metastases were negatively related to survival (Mandard TRG 3, 4, or 5: hazard ratio [HR], 1.94; 95% CI, 1.11 to 3.39; P = .0209; lymph node metastases: HR, 3.63; 95% CI, 1.88 to 7.0; P < .001). On multivariate analysis, only lymph node status was independently predictive of OS (HR, 3.36; 95% CI, 1.70 to 6.63; P < .001). Conclusion: Lymph node metastases and not pathologic response to chemotherapy was the only independent predictor of survival after chemotherapy plus resection in the MAGIC trial. Prospective evaluation of whether omitting postoperative chemotherapy and/or switching to a noncross-resistant regimen in patients with lymph node-positive disease whose tumor did not respond to preoperative epirubicin, cisplatin, and fluorouracil may be appropriate

A novel MYCN-specific antigene oligonucleotide deregulates mitochondria and inhibits tumor growth in MYCN-amplified neuroblastoma

Approximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood. Although N-Myc is a known driver of the disease, it remains a target for which no therapeutic drug exists. Here, we evaluated a novel MYCN-specific antigene PNA oligonucleotide (BGA002) in MYCN-amplified (MNA) or MYCN-expressing neuroblastoma and investigated the mechanism of its antitumor activity. MYCN mRNA and cell viability were reduced in a broad set of neuroblastoma cell lines following BGA002 treatment. Furthermore, BGA002 decreased N-Myc protein levels and apoptosis in MNA neuroblastoma. Analysis of gene expression data from patients with neuroblastoma revealed that MYCN was associated with increased reactive oxygen species (ROS), downregulated mitophagy, and poor prognosis. Inhibition of MYCN caused profound mitochondrial damage in MNA neuroblastoma cells through downregulation of the mitochondrial molecular chaperone TRAP1, which subsequently increased ROS. Correspondingly, inhibition of MYCN reactivated mitophagy. Systemic administration of BGA002 downregulated N-Myc and TRAP1, with a concomitant decrease in MNA neuroblastoma xenograft tumor weight. In conclusion, this study highlights the role of N-Myc in blocking mitophagy in neuroblastoma and in conferring protection to ROS in mitochondria through upregulation of TRAP1. BGA002 is a potently improved MYCN-specific antigene oligonucleotide that reverts N-Myc\u2013dysregulated mitochondrial pathways, leading to loss of the protective effect of N-Myc against mitochondrial ROS. Significance: A second generation antigene peptide oligonucleotide targeting MYCN induces mitochondrial damage and inhibits growth of MYCN-amplified neuroblastoma cells