Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Coupling of free surface and groundwater flows

In this paper we present some preliminary results about the coupling of shallow water equations for free surface flows and Darcy equation for groundwater flows. A suitable set of interface conditions is discussed: the Beavers and Joseph formula for the bottom stress is used. An iterative algorithm to solve the coupled problem is proposed and some numerical results are presented.     

Analysis of liver regeneration in mice lacking type 1 or type 2 tumor necrosis factor receptor: requirement for type 1 but not type 2 receptor

We used KO mice lacking either TNF receptor 1 (TNFR-1) or receptor 2 (TNFR-2) to determine whether signaling at the start of liver regeneration after partial hepatectomy (PH) involves only one or both TNF receptors and to analyze in more detail the abnormalities caused by lack of TNFR-1 receptor, which is required for the initiation of liver regeneration. Lack of TNFR-2 had little effect on NF-kappaB and STAT3 binding, and no effect in interleukin-6 production after PH, but caused a delay in AP-1 and C/EBP binding and in the expression of c-jun and c-myc messenger RNA (mRNA). In contrast to mice lacking TNFR-1, which had deficient hepatocyte DNA synthesis and massive lipid accumulation in hepatocytes, TNFR-2 KO mice had normal liver structure and similar levels of hepatocyte DNA replication as those of wild type mice. We conclude that TNFR-1, but not TNFR-2, is necessary for liver regeneration, and that NF-kappaB and STAT3 binding are activated by signals transduced by TNFR-1. Inhibition of AP-1 and C/EBP binding and in the expression of c-jun and c-myc mRNA in the first 4 hours after PH, as well as the apparent lack of Fos in AP-1 complexes, had no effect on the timing or extent of DNA replication.     

The effect of tetraethylammonium cation adsorption on the pzc of the mercury—perchloric acid interphase

The acid activity dependence of pzc for the mercury—perchloric acid aqueous solution interphase was studied, and the results compared with previously reported values. Then, the pzc shift caused by tetraethylammonium (TEA) perchlorate addition to constant activity perchloric acid solutions is reported, and an expression for the Esin—Markov coefficient is given. The need for using activity values is discussed on the basis of quantitive data.     

Differential Electrochemical Conductance Imaging at the Nanoscale

Electron transfer in proteins is essential in crucial biological processes. Although the fundamental aspects of biological electron transfer are well characterized, currently there are no experimental tools to determine the atomic‐scale electronic pathways in redox proteins, and thus to fully understand their outstanding efficiency and environmental adaptability. This knowledge is also required to design and optimize biomolecular electronic devices. In order to measure the local conductance of an electrode surface immersed in an electrolyte, this study builds upon the current–potential spectroscopic capacity of electrochemical scanning tunneling microscopy, by adding an alternating current modulation technique. With this setup, spatially resolved, differential electrochemical conductance images under bipotentiostatic control are recorded. Differential electrochemical conductance imaging allows visualizing the reversible oxidation of an iron electrode in borate buffer and individual azurin proteins immobilized on atomically flat gold surfaces. In particular, this method reveals submolecular regions with high conductance within the protein. The direct observation of nanoscale conduction pathways in redox proteins and complexes enables important advances in biochemistry and bionanotechnology.     

Distance browsing in distributed multimedia databases

The state of the art of searching for non-text data (e.g., images) is to use extracted metadata annotations or text, which might be available as a related information. However, supporting real content-based audiovisual search, based on similarity search on features, is significantly more expensive than searching for text. Moreover, such search exhibits linear scalability with respect to the dataset size, so parallel query execution is needed.In this paper, we present a Distributed Incremental Nearest Neighbor algorithm (DINN) for finding closest objects in an incremental fashion over data distributed among computer nodes, each able to perform its local Incremental Nearest Neighbor (local-INN) algorithm. We prove that our algorithm is optimum with respect to both the number of involved nodes and the number of local-INN invocations. An implementation of our DINN algorithm, on a real P2P system called MCAN, was used for conducting an extensive experimental evaluation on a real-life dataset.The proposed algorithm is being used in two running projects: SAPIR and NeP4B.     

On the relation among answer set solvers

In this paper, we study the relation among Answer Set Programming (ASP) systems from a computational point of view. We consider smodels, dlv, and cmodels ASP systems based on stable model semantics, the first two being native ASP systems and the last being a SAT-based system. We first show that smodels, dlv, and cmodels explore search trees with the same branching nodes (assuming, of course, a same branching heuristic) on the class of tight logic programs. Leveraging on the fact that SAT-based systems rely on the deeply studied Davis–Logemann–Loveland (dll) algorithm, we derive new complexity results for the ASP procedures. We also show that on nontight programs the SAT-based systems are computationally different from native procedures, and the latter have computational advantages. Moreover, we show that native procedures can guarantee the “correctness” of a reported solution when reaching the leaves of the search trees (i.e., no stability check is needed), while this is not the case for SAT-based procedures on nontight programs. A similar advantage holds for dlv in comparison with smodels if the “well-founded” operator is disabled and only Fitting’s operator is used for negative inferences. We finally study the “cost” of achieving such advantages and comment on to what extent the results presented extend to other systems.     

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