Learning hierarchical probabilistic logic programs

Machine Learning - Probabilistic logic programming (PLP) combines logic programs and probabilities. Due to its expressiveness and simplicity, it has been considered as a powerful tool for learning...     

Complementary Effects of Carbamylated and Citrullinated LL37 in Autoimmunity and Inflammation in Systemic Lupus Erythematosus

LL37 acts as T-cell/B-cell autoantigen in Systemic lupus erythematosus (SLE) and psoriatic disease. Moreover, when bound to “self” nucleic acids, LL37 acts as “danger signal,” leading to type I interferon (IFN-I)/pro-inflammatory factors production. T-cell epitopes derived from citrullinated-LL37 act as better antigens than unmodified LL37 epitopes in SLE, at least in selected HLA-backgrounds, included the SLE-associated HLA-DRB1*1501/HLA-DRB5*0101 backgrounds. Remarkably, while “fully-citrullinated” LL37 acts as better T-cell-stimulator, it loses DNA-binding ability and the associated “adjuvant-like” properties. Since LL37 undergoes a further irreversible post-translational modification, carbamylation and antibodies to carbamylated self-proteins other than LL37 are present in SLE, here we addressed the involvement of carbamylated-LL37 in autoimmunity and inflammation in SLE. We detected carbamylated-LL37 in SLE-affected tissues. Most importantly, carbamylated-LL37-specific antibodies and CD4 T-cells circulate in SLE and both correlate with disease activity. In contrast to “fully citrullinated-LL37,” “fully carbamylated-LL37” maintains both innate and adaptive immune-cells’ stimulatory abilities: in complex with DNA, carbamylated-LL37 stimulates plasmacytoid dendritic cell IFN-α production and B-cell maturation into plasma cells. Thus, we report a further example of how different post-translational modifications of a self-antigen exert complementary effects that sustain autoimmunity and inflammation, respectively. These data also show that T/B-cell responses to carbamylated-LL37 represent novel SLE disease biomarkers.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O₂-CNN), and compared them with nitrogen CNN (N₂-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O₂, 5% CO₂ and 74% N₂) and their protective effects during hypoxia (1% O₂, 5% CO₂ and 94% N₂) and reoxygenation (21% O₂, 5% CO₂ and 74% N₂) were studied. Neither O₂-CNN nor N₂-CNN has any effect on the growth curve during normoxia. However, O₂-CNN applied before hypoxia induces a 15–30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N₂-CNN. O₂-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.     

Design of Lu2O3-reinforced Cf/SiC-ZrB2-ZrC ultra-high temperature ceramic matrix composites: Wetting and interfacial reactivity by ZrSi2 based alloys

The wettability and infiltration of molten ZrSi₂ and ZrSi₂-Lu₂O₃ alloys into C_f/SiC and B₄C-infiltrated C_f/SiC composites were investigated to understand the interfacial interactions that occur during the development of C_f/SiC-ZrC and C_f/SiC-ZrB₂-ZrC-Lu₂O₃ materials. A significant evaporation of Si from the liquid affected the wetting behaviour of the alloy when tested in a vacuum at 1670 °C. The better wetting and spreading of the alloy over the surface was observed for the composites with lower overall porosity (12 %). On the other hand, the formation of an outer dense layer, followed up by the uniform infiltrated region up to ～ 1 mm was observed for the C_f/SiC with higher porosity (21 %). The infiltrated alloy reacted with SiC matrix to form ZrC or with B₄C-infiltrated SiC matrix to form ZrB₂-ZrC-SiC. The Lu₂O₃ particles were not wetted by the melt, and were pushed away of the reaction zone by the solidification front.     

An optimization framework for “build-or-buy” decisions in software architecture

Building a software architecture that meets functional requirements is a quite consolidated activity, whereas keeping high quality attributes is still an open challenge. In this paper we introduce an optimization framework that supports the decision whether to buy software components or to build them in-house upon designing a software architecture. We devise a non-linear cost/quality optimization model based on decision variables indicating the set of architectural components to buy and to build in order to minimize the software cost while keeping satisfactory values of quality attributes. From this point of view, our tool can be ideally embedded into a Cost Benefit Analysis Method to provide decision support to software architects. The novelty of our approach consists in building costs and quality attributes on a common set of decision variables related to software development. We start from a special case of the framework where the quality constraints are related to the delivery time and the product reliability, and the model solution also devises the amount of unit testing to be performed on built components. We generalize the framework formulation to represent a broader class of architectural cost-minimization problems under quality constraints, and discuss advantages and limitations of such approach.     

Outlier detection using default reasoning

Default logics are usually used to describe the regular behavior and normal properties of domain elements. In this paper we suggest, conversely, that the framework of default logics can be exploited for detecting outliers. Outliers are observations expressed by sets of literals that feature unexpected semantical characteristics. These sets of literals are selected among those explicitly embodied in the given knowledge base. Hence, essentially we perceive outlier detection as a knowledge discovery technique. This paper defines the notion of outlier in two related formalisms for specifying defaults: Reiter's default logic and extended disjunctive logic programs. For each of the two formalisms, we show that finding outliers is quite complex. Indeed, we prove that several versions of the outlier detection problem lie over the second level of the polynomial hierarchy. We believe that a thorough complexity analysis, as done here, is a useful preliminary step towards developing effective heuristics and exploring tractable subsets of outlier detection problems.     

Impurity scattering in quantum wires with Coulomb interaction

The Coulomb 1/r-interaction plays an important role in quantum wires. We study the interplay between this long range interaction and impurity. For a single band quantum wire, we find that the transport properties are strongly modified. The linear conductance G is found to vanish with temperature as G exp[- ln^3/2(1/T)]and the current-voltage characteristics acquires a threshold-like behavior.We are grateful to A. Dyugaev for interesting discussions.     

A systematic literature review on IoT-aware business process modeling views,requirements and notations

Software and Systems Modeling - The Internet of things has been adopted in several sectors both influencing how people work and enhancing organizations’ business processes. This resulted in...     

Analysis of Non-Equilibrium Fluctuations In A Ternary Liquid Mixture

From the benchmark values of the diffusion and thermodiffusion coefficients of the tetralin, isobutylbenzene and n-dodecane ternary mixture, and the published optical contrast factors, we have evaluated the theoretical amplitudes of the two composition modes of the refractive-index fluctuations. Shadowgraph experiments have been performed on ground, where the current theory is expected to be correct only for large wave vectors. Two decay times have been observed experimentally. The fastest one being related to the thermal diffusivity of the mixture, while the slower one to mass diffusion. Hence, it has not been possible to distinguish the two eigenvalues of the mass diffusion matrix, a problem also encountered in traditional light-scattering with ternary mixtures of similar-size molecules. Thus, to compare the measured Intermediate Scattering Function with theory, we fix the amplitudes and decay rates to the benchmark values, use the wave number as a fitting parameter, and compare it to the experimental wave number. The good agreement between theory and experiments for the larger wave numbers validates the theory developed for the microgravity conditions.