The sparse Blume-Emery-Griffiths model of associative memories

We analyze the Blume-Emery-Griffiths (BEG) associative memory with sparse patterns and at zero temperature. We give bounds on its storage capacity provided that we want the stored patterns to be fixed points of the retrieval dynamics. We compare our results to that of other models of sparse neural networks and show that the BEG model has a superior performance compared to them.Comment: 23 p

Gradation of Algebras of Curves by the Winding Number

We construct a new grading on the Goldman Lie algebra of a closed oriented surface by the winding number. This grading induces a grading on the HOMFLY-PT skein algebra and related algebras. Our work supports the conjectures of B. Cooper and P. SamuelsonComment: Changed acknowledgments and Definition 2.

Study of Xenon Mobility in the Two Forms of MIL-53(Al) Using Solid-State NMR Spectroscopy

The Al-based metal–organic framework (MOF) MIL-53­(Al) exhibits a structural transition between a large-pore (<i>lp</i>) form and a narrow-pore (<i>np</i>) one. Such change is induced by temperature, external pressure, or the adsorption of guest molecules. ¹²⁹Xe solid-state NMR experiments under static and magic-angle spinning (MAS) conditions have been used to study the <i>lp</i>–<i>np</i> transition in MIL-53­(Al) initially loaded with xenon gas under a pressure of 5 × 10⁴ Pa (at room temperature). The conversion of the <i>lp</i> form into the <i>np</i> one when the temperature decreases from 327 to 237 K and the reopening of the pores below 230 K are then observed. Furthermore, ¹H → ¹²⁹Xe cross-polarization under MAS (CPMAS) experiments demonstrate the possibility to observe the <i>np</i> phase at <i>T</i> ≤ 230 K, while the <i>lp</i> one is unseen because the xenon residence time is too short for successful cross-polarization transfer. Moreover, even for the <i>np</i> phase at 199 K, the xenon atoms still exhibit significant motion on time scale faster than a few milliseconds. We prove the exchange of Xe atoms between the <i>lp</i> and <i>np</i> forms at room temperature with the two-dimensional (2D) ¹²⁹Xe EXchange SpectroscopY (EXSY) NMR method. Using ¹²⁹Xe selective inversion recovery (SIR) experiments, the rate for this exchange has been measured at 43 ± 6 s^–1

Developing an acoustic-phonetic characterization of dysarthric speech in French

- ISBN: 2-9517408-6-7 - Domaines: Phonetic Databases, Phonology, Person IdentificationInternational audienceThis paper presents the rationale, objectives and advances of an on-going project (the DesPho-APaDy project funded by the French National Agency of Research) which aims to provide a systematic and quantified description of French dysarthric speech, over a large population of patients and three dysarthria types (related to the parkinson's disease, the Amyotrophic Lateral Sclerosis disease, and a pure cerebellar alteration). The two French corpora of dysarthric patients, from which the speech data have been selected for analysis purposes, are firstly described. Secondly, this paper discusses and outlines the requirement of a structured and organized computerized platform in order to store, organize and make accessible (for selected and protected usage) dysarthric speech corpora and associated patients' clinical information (mostly disseminated in different locations: labs, hospitals, ...). The design of both a computer database and a multi-field query interface is proposed for the clinical context. Finally, advances of the project related to the selection of the population used for the dysarthria analysis, the preprocessing of the speech files, their orthographic transcription and their automatic alignment are also presented

Heterogeneity of genomic evolution and mutational profiles in multiple myeloma.

Multiple myeloma is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Here we use whole-exome sequencing, copy-number profiling and cytogenetics to analyse 84 myeloma samples. Most cases have a complex subclonal structure and show clusters of subclonal variants, including subclonal driver mutations. Serial sampling reveals diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Diverse processes contribute to the mutational repertoire, including kataegis and somatic hypermutation, and their relative contribution changes over time. We find heterogeneity of mutational spectrum across samples, with few recurrent genes. We identify new candidate genes, including truncations of SP140, LTB, ROBO1 and clustered missense mutations in EGR1. The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment

Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network

During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events

Minimal residual disease in Myeloma: Application for clinical care and new drug registration

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes

Trypacidin, a Spore-Borne Toxin from Aspergillus fumigatus, Is Cytotoxic to Lung Cells

Inhalation of Aspergillus fumigatus conidia can cause severe aspergillosis in immunosuppressed people. A. fumigatus produces a large number of secondary metabolites, some of which are airborne by conidia and whose toxicity to the respiratory tract has not been investigated. We found that spores of A. fumigatus contain five main compounds, tryptoquivaline F, fumiquinazoline C, questin, monomethylsulochrin and trypacidin. Fractionation of culture extracts using RP-HPLC and LC-MS showed that samples containing questin, monomethylsulochrin and trypacidin were toxic to the human A549 lung cell line. These compounds were purified and their structure verified using NMR in order to compare their toxicity against A549 cells. Trypacidin was the most toxic, decreasing cell viability and triggering cell lysis, both effects occurring at an IC50 close to 7 µM. Trypacidin toxicity was also observed in the same concentration range on human bronchial epithelial cells. In the first hour of exposure, trypacidin initiates the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H2O2). This oxidative stress triggers necrotic cell death in the following 24 h. The apoptosis pathway, moreover, was not involved in the cell death process as trypacidin did not induce apoptotic bodies or a decrease in mitochondrial membrane potential. This is the first time that the toxicity of trypacidin to lung cells has been reported