Approximate similarity retrieval with M-trees

Motivated by the urgent need to improve the efficiency of similarity queries, approximate similarity retrieval is investigated in the environment of a metric tree index called the M-tree. Three different approximation techniques are proposed, which show how to forsake query precision for improved performance. Measures are defined that can quantify the improvements in performance efficiency and the quality of approximations. The proposed approximation techniques are then tested on various synthetic and real-life files. The evidence obtained from the experiments confirms our hypothesis that a high-quality approximated similarity search can be performed at a much lower cost than that needed to obtain the exact results. The proposed approximation techniques are scalable and appear to be independent of the metric used. Extensions of these techniques to the environments of other similarity search indexes are also discussed. Received July 7, 1998 / Accepted October 13, 1998     

Scaling of energy dissipation in crushing and fragmentation: a fractal and statistical analysis based on particle size distribution

An extensive experimental investigation on concrete specimens under crushing and fragmentation over a large scale range (1:10) – exploring even very small specimen dimensions (1 cm) – was carried out to evaluate the influence of fragment size distribution on energy density dissipation and related size effect. To obtain a statistically significant fragment production as well as the total energy dissipated in a given specimen, the experimental procedure was unusually carried out up to a strain of approximately –95%, practically corresponding to the initial fragment compaction between the loading platens. The experimental fragment analysis suggests a fractal law for the distribution in particle size; this simply means that fragments derived from a given specimen appear geometrically self-similar at each observation scale. In addition, clear size effects on dissipated energy density are experimentally observed. Fractal concepts permit to quantify the correlation between fragment size distribution and size effect on dissipated energy density, the latter being governed by the total surface area of produced fragments. The experimental results agree with the proposed multi-scale interpretation satisfactorily.     

Design and Hydraulics of a Combined Storm Overflow Structure

Storm overflow structures in combined sewers are used to separate sewage from storm water. For subcritical approach flow, sideweirs are currently used; however, they often behave hydraulically poor. This study was conducted to explore a combined storm overflow structure able to improve the hydraulic performance of sewer sideweirs. Such a structure consists of a low-crested sideweir and a bottom opening just downstream from the sideweir end. First, the hydraulic design procedure is described, and then, based on laboratory experiments and by using the governing flow equations, the main hydraulic features are highlighted. The results indicate that the proposed device has advantageous characteristics in terms of hydraulic efficiency, reliability, and maintenance.     

Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun.     

A distributed simplex algorithm for degenerate linear programs and multi-agent assignments

In this paper we propose a novel distributed algorithm to solve degenerate linear programs on asynchronous peer-to-peer networks with distributed information structures. We propose a distributed version of the well-known simplex algorithm for general degenerate linear programs. A network of agents, running our algorithm, will agree on a common optimal solution, even if the optimal solution is not unique, or will determine infeasibility or unboundedness of the problem. We establish how the multi-agent assignment problem can be efficiently solved by means of our distributed simplex algorithm. We provide simulations supporting the conjecture that the completion time scales linearly with the diameter of the communication graph.     

Chiral Discrimination Mechanisms by Silylated-Acetylated Cyclodextrins: Superficial Interactions vs. Inclusion

Cyclodextrin derivatives constitute a powerful class of auxiliary agents for the discrimination of apolar chiral substrates. Both host–guest inclusion phenomena and interactions with the derivatizing groups located on the surface of the macrocycle could drive the enantiodiscrimination; thus, it is important to understand the role that these processes play in the rational design of new chiral selectors. The purpose of this study is to compare via nuclear magnetic resonance (NMR) spectroscopy the efficiency of silylated-acetylated α-, β-, and γ-cyclodextrins in the chiral discrimination of 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane (compound B) and methyl 2-chloropropionate (MCP). NMR DOSY (Diffusion Ordered SpectroscopY) experiments were conducted for the determination of the bound molar fractions and the association constants, whereas ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) measurements provided information on the hosts’ conformation and on the interaction phenomena with the guests. Compound B, endowed with fluorinated moieties, is not deeply included due to attractive Si-F interactions occurring at the external surface of the cyclodextrins. Therefore, a low selectivity toward the size of cyclodextrin cavity is found. By contrast, enantiodiscrimination of MCP relies on the optimal fitting between the size of the guest and that of the cyclodextrin cavity.     

Delineating Purinergic Signaling in Drosophila

Simplistic models can aid in discovering what is important in the context of normal and pathological behavior. First recognized as a genetic model more than 100 years ago, to date, fruit flies (Drosophila melanogaster) still remain an astonishingly good laboratory stand-in for scientists to study development and physiology and to investigate the molecular mechanisms of human diseases. This is because fruit flies indeed represent a simplistic model. Furthermore, about 75% of human disease-related genes have their counterparts in the Drosophila genome, added to the fact that fruit flies are inexpensive and extremely easy to maintain, being invertebrates and, moreover, lacking any ethical concern issues. Purinergic signaling is, by definition, mediated by extracellular purinergic ligands, among which ATP represents the prototype molecule. A key feature that has progressively emerged when dissecting the purinergic mechanisms is the multilayer and dynamic nature of the signaling sustained by purinergic ligands. Indeed, these last are sequentially metabolized by several different ectonucleotidases, which generate the ligands that simultaneously activate several different purinergic receptors. Since significant purinergic actions have also been described in Drosophila, the aim of the present work is to provide a comprehensive picture of the purinergic events occurring in fruit flies.     

IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine

Coronavirus SARS-CoV-2 has represented, and still represents, a real challenge from a clinical, diagnostic and therapeutic point of view. During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity. In this work, we analyse current evidence regarding the immunological role of IL-33 in patients affected by COVID-19, to evaluate not only the clinical impact correlated to its production but also to identify possible future immunological therapies that can block the most expressed inflammatory molecules, preventing worsening of the disease and saving patient lives.     

Bi-Allelic Mutations in Zebrafish pank2 Gene Lead to Testicular Atrophy and Perturbed Behavior without Signs of Neurodegeneration

Coenzyme A (CoA) is an essential cofactor in all living organisms, being involved in a large number of chemical reactions. Sequence variations in pantothenate kinase 2 (PANK2), the first enzyme of CoA biosynthesis, are found in patients affected by Pantothenate Kinase Associated Neurodegeneration (PKAN), one of the most common forms of neurodegeneration, with brain iron accumulation. Knowledge about the biochemical and molecular features of this disorder has increased a lot in recent years. Nonetheless, the main culprit of the pathology is not well defined, and no treatment option is available yet. In order to contribute to the understanding of this disease and facilitate the search for therapies, we explored the potential of the zebrafish animal model and generated lines carrying biallelic mutations in the pank2 gene. The phenotypic characterization of pank2-mutant embryos revealed anomalies in the development of venous vascular structures and germ cells. Adult fish showed testicular atrophy and altered behavioral response in an anxiety test but no evident signs of neurodegeneration. The study suggests that selected cell and tissue types show a higher vulnerability to pank2 deficiency in zebrafish. Deciphering the biological basis of this phenomenon could provide relevant clues for better understanding and treating PKAN.