Learning Ordinal Preferences on Multiattribute Domains: the Case of CP-nets

International audienceA recurrent issue in decision making is to extract a preference structure by observing the user's behavior in different situations. In this paper, we investigate the problem of learning ordinal preference orderings over discrete multi-attribute, or combinatorial, domains. Specifically, we focus on the learnability issue of conditional preference networks, or CP- nets, that have recently emerged as a popular graphical language for representing ordinal preferences in a concise and intuitive manner. This paper provides results in both passive and active learning. In the passive setting, the learner aims at finding a CP-net compatible with a supplied set of examples, while in the active setting the learner searches for the cheapest interaction policy with the user for acquiring the target CP-net

Pre-Excitation Studies for Rubidium-Plasma Generation

The key element in the Proton-Driven-Plasma-Wake-Field-Accelerator (AWAKE) project is the generation of highly uniform plasma from Rubidium vapor. The standard way to achieve full ionization is to use high power laser which can assure the over-barrier-ionization (OBI) along the 10 meters long active region. The Wigner-team in Budapest is investigating an alternative way of uniform plasma generation. The proposed Resonance Enhanced Multi Photon Ionization (REMPI) scheme probably can be realized by much less laser power. In the following the resonant pre-excitations of the Rb atoms are investigated, theoretically and the status report about the preparatory work on the experiment are presented.Comment: 8 pages, 6 figures, submitted to Nucl. Inst. and Meth. in Phys. Res.

A molecular basis for neurofibroma-associated skeletal manifestations in NF1

Purpose: Plexiform neurofibromas (pNF) develop in children with neurofibromatosis type 1 (NF1) and can be associated with several skeletal comorbidities. Preclinical mouse studies revealed Nf1 deficiency in osteoprogenitor cells disrupts, in a MEK-dependent manner, pyrophosphate (PPi) homeostasis and skeletal mineralization. The etiology of NF-associated skeletal manifestations remains unknown. Methods: We used mouse models of NF1 neurofibromas to assess bone mineralization of skeletal structures adjacent to tumors. Expression of genes involved in pyrophosphate homeostasis was assessed in mouse and human NF tumors and Schwann cell cultures. We used dual-energy X-ray absorptiometry (DXA) to assess tumor-associated changes in bone mineral density (BMD) in an individual with NF1 following treatment with the MEK inhibitor selumetinib. Results: We detected increased nonmineralized bone surfaces adjacent to tumors in mouse models of NF1 neurofibromas. Expression of Enpp1, a PPi-generating ectophosphatase, and ANKH, a PPi transporter, was increased in mouse and human neurofibroma-derived tissues and Schwann cells, respectively. In one patient, tumor-associated reductions in BMD were partially rescued following therapy with selumetinib. Conclusion: Results indicate that NF-associated skeletal pathologies in NF1 are associated with dysregulated pyrophosphate homeostasis in adjacent NF tumors and suggest that treatment of NFs with MEK inhibitors may improve skeletal manifestations of the disease

Efficient and accurate modeling of electron photoemission in nanostructures with TDDFT

We derive and extend the time-dependent surface-flux method introduced in [L. Tao, A. Scrinzi, New J. Phys. 14, 013021 (2012)] within a time-dependent density-functional theory (TDDFT) formalism and use it to calculate photoelectron spectra and angular distributions of atoms and molecules when excited by laser pulses. We present other, existing computational TDDFT methods that are suitable for the calculation of electron emission in compact spatial regions, and compare their results. We illustrate the performance of the new method by simulating strong-field ionization of C60 fullerene and discuss final state effects in the orbital reconstruction of planar organic molecules

Intense ultrashort terahertz pulses: generation and applications

TOPICAL REVIEW: Ultrashort terahertz pulses derived from femtosecond table-top sources have become a valuable tool for time-resolved spectroscopy during the last two decades. Until recently, the pulse energies and field strengths of these pulses have been generally too low to allow for the use as pump pulses or the study of nonlinear effects in the terahertz range. In this review article we will describe methods of generation of intense single cycle terahertz pulses with emphasis on optical rectification using the tilted-pulse-front pumping technique. We will also discuss some applications of these intense pulses in the emerging field of nonlinear terahertz spectroscopy

Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial

Neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNs) are progressive, multicellular neoplasms that cause morbidity and may transform to sarcoma. Treatment of Nf1fl/fl;Postn-Cre mice with cabozantinib, an inhibitor of multiple tyrosine kinases, caused a reduction in PN size and number and differential modulation of kinases in cell lineages that drive PN growth. Based on these findings, the Neurofibromatosis Clinical Trials Consortium conducted a phase II, open-label, nonrandomized Simon two-stage study to assess the safety, efficacy and biologic activity of cabozantinib in patients ≥16 years of age with NF1 and progressive or symptomatic, inoperable PN ( NCT02101736 ). The trial met its primary outcome, defined as ≥25% of patients achieving a partial response (PR, defined as ≥20% reduction in target lesion volume as assessed by magnetic resonance imaging (MRI)) after 12 cycles of therapy. Secondary outcomes included adverse events (AEs), patient-reported outcomes (PROs) assessing pain and quality of life (QOL), pharmacokinetics (PK) and the levels of circulating endothelial cells and cytokines. Eight of 19 evaluable (42%) trial participants achieved a PR. The median change in tumor volume was 15.2% (range, +2.2% to -36.9%), and no patients had disease progression while on treatment. Nine patients required dose reduction or discontinuation of therapy due to AEs; common AEs included gastrointestinal toxicity, hypothyroidism, fatigue and palmar plantar erythrodysesthesia. A total of 11 grade 3 AEs occurred in eight patients. Patients with PR had a significant reduction in tumor pain intensity and pain interference in daily life but no change in global QOL scores. These data indicate that cabozantinib is active in NF1-associated PN, resulting in tumor volume reduction and pain improvement

Modulating mitophagy in mitochondrial disease

Mitochondrial diseases may result from mutations in the maternally-inherited mitochondrial DNA (mtDNA) or from mutations in nuclear genes encoding mitochondrial proteins. Their bi-genomic nature makes mitochondrial diseases a very heterogeneous group of disorders that can present at any age and can affect any type of tissue. The autophagic-lysosomal degradation pathway plays an important role in clearing dysfunctional and redundant mitochondria through a specific quality control mechanism termed mitophagy. Mitochondria could be targeted for autophagic degradation for a variety of reasons including basal turnover for recycling, starvation induced degradation, and degradation due to damage. While the core autophagic machinery is highly conserved and common to most pathways, the signaling pathways leading to the selective degradation of damaged mitochondria are still not completely understood. Type 1 mitophagy due to nutrient starvation is dependent on PI3K (phosphoinositide 3-kinase) for autophagosome formation but independent of mitophagy proteins, PINK1 (PTEN-induced putative kinase 1) and Parkin. Whereas type 2 mitophagy that occurs due to damage is dependent on PINK1 and Parkin but does not require PI3K. Autophagy and mitophagy play an important role in human disease and hence could serve as therapeutic targets for the treatment of mitochondrial as well as neurodegenerative disorders. Therefore, we reviewed drugs that are known modulators of autophagy (AICAR and metformin) and may effect this by activating the AMP-activated protein kinase signaling pathways. Furthermore, we reviewed data available on supplements, such as Coenzyme Q and the quinone idebenone, that we assert rescue increased mitophagy in mitochondrial disease by benefiting mitochondrial function