First IJCAI International Workshop on Graph Structures for Knowledge Representation and Reasoning (GKR@IJCAI'09)

International audienceThe development of effective techniques for knowledge representation and reasoning (KRR) is a crucial aspect of successful intelligent systems. Different representation paradigms, as well as their use in dedicated reasoning systems, have been extensively studied in the past. Nevertheless, new challenges, problems, and issues have emerged in the context of knowledge representation in Artificial Intelligence (AI), involving the logical manipulation of increasingly large information sets (see for example Semantic Web, BioInformatics and so on). Improvements in storage capacity and performance of computing infrastructure have also affected the nature of KRR systems, shifting their focus towards representational power and execution performance. Therefore, KRR research is faced with a challenge of developing knowledge representation structures optimized for large scale reasoning. This new generation of KRR systems includes graph-based knowledge representation formalisms such as Bayesian Networks (BNs), Semantic Networks (SNs), Conceptual Graphs (CGs), Formal Concept Analysis (FCA), CPnets, GAI-nets, all of which have been successfully used in a number of applications. The goal of this workshop is to bring together the researchers involved in the development and application of graph-based knowledge representation formalisms and reasoning techniques

Risk factors for sporadic listeriosis: a systematic review and meta-analysis

Listeriosis is a major public health concern associated with high hospitalization and mortality rates. The objective of this work was to summarize evidence on the associations between risk factors and sporadic cases by meta-analysing outcomes from currently published case-control studies. Suitable scientific articles were identified through systematic literature search, and subjected to a methodological quality assessment. From each study, odds-ratio (OR) measures as well as study characteristics such as population type, design, type of model and risk factor hierarchy were extracted. Mixed-effects meta-analysis models were adjusted by population type to appropriate data partitions. Twelve primary studies investigating sporadic listeriosis conducted between 1985 and 2013 passed through a quality assessment stage. These studies provided 226 OR considered for meta-analysis. According to the meta-analysis, the main risk factor for acquiring listeriosis is suffering from an immunocompromising disease. In relation to the food exposures, this meta-analysis confirmed known risk factors such as consumption of RTE dairy, seafood and processed meat and underlined new food vehicles as fruits and vegetables, recently involved in outbreaks. There were not enough data to appraise travel, animal-contact and person-to-person as transmission pathways for listeriosis. These results will allow refining the case-control studies in the aim of improving risk factors characterisation for listeriosis in the susceptible population.U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). U. Gonzales- Barron also thanks FCT, P.I., for the institutional scientific employment program.info:eu-repo/semantics/publishedVersio

Lock-in thermography as a rapid and reproducible thermal characterization method for magnetic nanoparticles

Lock-in thermography (LIT) is a sensitive imaging technique generally used in engineering and materials science (e.g. detecting defects in composite materials). However, it has recently been expanded for investigating the heating power of nanomaterials, such as superparamagnetic iron oxide nanoparticles (SPIONs). Here we implement LIT as a rapid and reproducible method that can evaluate the heating potential of various sizes of SPIONs under an alternating magnetic field (AMF), as well as the limits of detection for each particle size. SPIONs were synthesized via thermal decomposition and stabilized in water via a ligand transfer process. Thermographic measurements of SPIONs were made by stimulating particles of varying sizes and increasing concentrations under an AMF. Furthermore, a commercially available SPION sample was included as an external reference. While the size dependent heating efficiency of SPIONs has been previously described, our objective was to probe the sensitivity limits of LIT. For certain size regimes it was possible to detect signals at concentrations as low as 0.1 mg Fe/mL. Measuring at different concentrations enabled a linear regression analysis and extrapolation of the limit of detection for different size nanoparticles

TFEB regulates lysosomal proteostasis

Loss-of-function diseases are often caused by destabilizing mutations that lead to protein misfolding and degradation. Modulating the innate protein homeostasis (proteostasis) capacity may lead to rescue of native folding of the mutated variants, thereby ameliorating the disease phenotype. In lysosomal storage disorders (LSDs), a number of highly prevalent alleles have missense mutations that do not impair the enzyme's catalytic activity but destabilize its native structure, resulting in the degradation of the misfolded protein. Enhancing the cellular folding capacity enables rescuing the native, biologically functional structure of these unstable mutated enzymes. However, proteostasis modulators specific for the lysosomal system are currently unknown. Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs. We show that TFEB activation results in enhanced folding, trafficking and lysosomal activity of a severely destabilized glucocerebrosidase (GC) variant associated with the development of Gaucher disease (GD), the most common LSD. TFEB specifically induces the expression of GC and of key genes involved in folding and lysosomal trafficking, thereby enhancing both the pool of mutated enzyme and its processing through the secretory pathway. TFEB activation also rescues the activity of a β-hexosaminidase mutant associated with the development of another LSD, Tay–Sachs disease, thus suggesting general applicability of TFEB-mediated proteostasis modulation to rescue destabilizing mutations in LSDs. In summary, our findings identify TFEB as a specific regulator of lysosomal proteostasis and suggest that TFEB may be used as a therapeutic target to rescue enzyme homeostasis in LSDs

ASS1 Overexpression:A Hallmark of Sonic Hedgehog Hepatocellular Adenomas; Recommendations for Clinical Practice

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico-pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis

Proteomic and 3D structure analyses highlight the C/D box snoRNP assembly mechanism and its control

International audienceIn vitro, assembly of box C/D small nucleolar ribonucleoproteins (snoRNPs) involves the sequential recruitment of core proteins to snoRNAs. In vivo, however, assembly factors are required (NUFIP, BCD1, and the FISP90-R2TP complex), and it is unknown whether a similar sequential scheme applies. In this paper, we describe systematic quantitative stable isotope labeling by amino acids in cell culture proteomic experiments and the crystal structure of the core protein Snu 13p/15.5K bound to a fragment of the assembly factor Rsa1p/NUFIP. This revealed several unexpected features: (a) the existence of a protein-only pre-snoRNP complex containing five assembly factors and two core proteins, 15.5K and Nop58; (b) the characterization of ZNHIT3, which is present in the protein-only complex but gets released upon binding to C/D snoRNAs; (c) the dynamics of the R2TP complex, which,appears a to load/unload RuvBL AAA(+) adenosine triphosphatase from pre-snoRNPs; and (d) a potential mechanism for preventing premature activation of snoRNP catalytic activity. These data provide a framework for understanding the assembly of box C/D snoRNPs

A pair of TESS planets spanning the radius valley around the nearby mid-M dwarf LTT 3780

We present the confirmation of two new planets transiting the nearby mid-M dwarf LTT 3780 (TIC 36724087, TOI-732, $V=13.07$, $K_s=8.204$, $R_s$=0.374 R$_{\odot}$, $M_s$=0.401 M$_{\odot}$, d=22 pc). The two planet candidates are identified in a single TESS sector and are validated with reconnaissance spectroscopy, ground-based photometric follow-up, and high-resolution imaging. With measured orbital periods of $P_b=0.77$ days, $P_c=12.25$ days and sizes $r_{p,b}=1.33\pm 0.07$ R$_{\oplus}$, $r_{p,c}=2.30\pm 0.16$ R$_{\oplus}$, the two planets span the radius valley in period-radius space around low mass stars thus making the system a laboratory to test competing theories of the emergence of the radius valley in that stellar mass regime. By combining 63 precise radial-velocity measurements from HARPS and HARPS-N, we measure planet masses of $m_{p,b}=2.62^{+0.48}_{-0.46}$ M$_{\oplus}$ and $m_{p,c}=8.6^{+1.6}_{-1.3}$ M$_{\oplus}$, which indicates that LTT 3780b has a bulk composition consistent with being Earth-like, while LTT 3780c likely hosts an extended H/He envelope. We show that the recovered planetary masses are consistent with predictions from both photoevaporation and from core-powered mass loss models. The brightness and small size of LTT 3780, along with the measured planetary parameters, render LTT 3780b and c as accessible targets for atmospheric characterization of planets within the same planetary system and spanning the radius valley.Comment: Accepted to AJ. 8 figures, 6 tables. CSV file of the RV measurements (i.e. Table 2) are included in the source cod

K2-291b:A rocky super-Earth in a 2.2 day orbit

K2-291 (EPIC 247418783) is a solar-type star with a radius of R_star = 0.899 $\pm$ 0.034 R_sun and mass of M_star=0.934 $\pm$ 0.038 M_sun. From K2 C13 data, we found one super-Earth planet (R_p = 1.589+0.095-0.072 R_Earth) transiting this star on a short period orbit (P = 2.225177 +6.6e-5 -6.8e-5 days). We followed this system up with adaptive-optic imaging and spectroscopy to derive stellar parameters, search for stellar companions, and determine a planet mass. From our 75 radial velocity measurements using HIRES on Keck I and HARPS-N on Telescopio Nazionale Galileo, we constrained the mass of EPIC 247418783b to M_p = 6.49 $\pm$ 1.16 M_Earth. We found it necessary to model correlated stellar activity radial velocity signals with a Gaussian process in order to more accurately model the effect of stellar noise on our data; the addition of the Gaussian process also improved the precision of this mass measurement. With a bulk density of 8.84+2.50-2.03 g cm-3, the planet is consistent with an Earth-like rock/iron composition and no substantial gaseous envelope. Such an envelope, if it existed in the past, was likely eroded away by photo-evaporation during the first billion years of the star's lifetime.Comment: Accepted to AJ, 15 pages, 8 figure

An Ultra-short Period Rocky Super-Earth with a Secondary Eclipse and a Neptune-like Companion around K2-141

Ultra-short period (USP) planets are a class of low mass planets with periods shorter than one day. Their origin is still unknown, with photo-evaporation of mini-Neptunes and in-situ formation being the most credited hypotheses. Formation scenarios differ radically in the predicted composition of USP planets, it is therefore extremely important to increase the still limited sample of USP planets with precise and accurate mass and density measurements. We report here the characterization of an USP planet with a period of 0.28 days around K2-141 (EPIC 246393474), and the validation of an outer planet with a period of 7.7 days in a grazing transit configuration. We derived the radii of the planets from the K2 light curve and used high-precision radial velocities gathered with the HARPS-N spectrograph for mass measurements. For K2-141b we thus inferred a radius of $1.51\pm0.05~R_\oplus$ and a mass of $5.08\pm0.41~M_\oplus$, consistent with a rocky composition and lack of a thick atmosphere. K2-141c is likely a Neptune-like planet, although due to the grazing transits and the non-detection in the RV dataset, we were not able to put a strong constraint on its density. We also report the detection of secondary eclipses and phase curve variations for K2-141b. The phase variation can be modeled either by a planet with a geometric albedo of $0.30 \pm 0.06$ in the Kepler bandpass, or by thermal emission from the surface of the planet at $\sim$3000K. Only follow-up observations at longer wavelengths will allow us to distinguish between these two scenarios.Comment: 16 pages, 10 figures., accepted for publication in A