ARAXA: Storing and managing Active XML documents

Active XML (AXML) documents combine extensional XML data with intentional data defined through Web service calls. The dynamic properties of these documents pose challenges to both storage and data materialization techniques. In this paper, we present ARAXA, a non-intrusive approach to store and manage AXML documents. We also define a methodology to materialize AXML documents at query time. The storage approach of ARAXA is based on plain relational tables and user-defined functions of Object-Relational DBMS to trigger the service calls. By using a DBMS we benefit from efficient storage tools and query optimization. Approaches without DBMS support have to process XML in main memory or provide for virtual memory solutions. One of the main advantages of ARAXA is that AXML documents do not need to be loaded into main memory at query processing time. This is crucial when dealing with large documents. The experimental results with ARAXA prototype show that our approach is scalable and capable of dealing with large AXML documents.     

The Inhibition of DNA Viruses by the Amphibian Antimicrobial Peptide Temporin G: A Virological Study Addressing HSV-1 and JPCyV

Herpes simplex virus type-1 (HSV-1) and John Cunningham polyomavirus (JCPyV) are widely distributed DNA viruses causing mainly asymptomatic infection, but also mild to very severe diseases, especially when these viruses reach the brain. Some drugs have been developed to inhibit HSV-1 replication in host cells, but their prolonged use may induce resistance phenomena. In contrast, to date, there is no cure for JCPyV. The search for alternative drugs that can reduce viral infections without undermining the host cell is moving toward antimicrobial peptides (AMPs) of natural occurrence. These include amphibian AMPs belonging to the temporin family. Herein, we focus on temporin G (TG), showing that it strongly affects HSV-1 replication by acting either during the earliest stages of its life cycle or directly on the virion. Computational studies have revealed the ability of TG to interact with HSV-1 glycoprotein B. We also found that TG reduced JCPyV infection, probably affecting both the earliest phases of its life cycle and the viral particle, likely through an interaction with the viral capsid protein VP1. Overall, our results are promising for the development of short naturally occurring peptides as antiviral agents used to counteract diseases related to HSV-1 and JCPyV.     

Discovery of New 3,3-Diethylazetidine-2,4-dione Based Thiazoles as Nanomolar Human Neutrophil Elastase Inhibitors with Broad-Spectrum Antiproliferative Activity

A series of 3,3-diethylazetidine-2,4-dione based thiazoles 3a–3j were designed and synthesized as new human neutrophil elastase (HNE) inhibitors in nanomolar range. The representative compounds 3c, 3e, and 3h exhibit high HNE inhibitory activity with IC₅₀ values of 35.02–44.59 nM, with mixed mechanism of action. Additionally, the most active compounds 3c and 3e demonstrate high stability under physiological conditions. The molecular docking study showed good correlation of the binding energies with the IC₅₀ values, suggesting that the inhibition properties are largely dependent on the stage of ligand alignment in the binding cavity. The inhibition properties are correlated with the energy level of substrates of the reaction of ligand with Ser195. Moreover, most compounds showed high and broad-spectrum antiproliferative activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast adenocarcinoma (MDA-MB-231), and urinary bladder carcinoma (UMUC-3), with IC₅₀ values of 4.59–9.86 μM. Additionally, compounds 3c and 3e can induce cell cycle arrest at the G2/M phase and apoptosis via caspase-3 activation, leading to inhibition of A549 cell proliferation. These findings suggest that these new types of drugs could be used to treat cancer and other diseases in which immunoreactive HNE is produced.     

Protein Abundance of Drug Transporters in Human Hepatitis C Livers

Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child–Pugh class A (n = 30), B (n = 21), and C (n = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection. P-gp, MRP1, BCRP, and OATP1B3 protein abundances were upregulated, whereas those of MRP2, MRP4, NTCP, OATP2B1, and OCT1 were downregulated in all HCV samples. The observed changes started to be seen in the Child–Pugh class A livers, i.e., upregulation of P-gp and MRP1 and downregulation of MRP2, MRP4, BCRP, and OATP1B3. In the case of NTCP, OATP2B1, and OCT1, a decrease in the protein levels was observed in the class B livers. In the class C livers, no other changes were noted than those in the class A and B patients. The results of the study demonstrate that drug transporter protein abundances are affected by the functional state of the liver in hepatitis C patients.     

MTCProv: a practical provenance query framework for many-task scientific computing

Scientific research is increasingly assisted by computer-based experiments. Such experiments are often composed of a vast number of loosely-coupled computational tasks that are specified and automated as scientific workflows. This large scale is also characteristic of the data that flows within such “many-task” computations (MTC). Provenance information can record the behavior of such computational experiments via the lineage of process and data artifacts. However, work to date has focused on lineage data models, leaving unsolved issues of recording and querying other aspects, such as domain-specific information about the experiments, MTC behavior given by resource consumption and failure information, or the impact of environment on performance and accuracy. In this work we contribute with MTCProv, a provenance query framework for many-task scientific computing that captures the runtime execution details of MTC workflow tasks on parallel and distributed systems, in addition to standard prospective and data derivation provenance. To help users query provenance data we provide a high level interface that hides relational query complexities. We evaluate MTCProv using an application in protein science, and describe how important query patterns such as correlations between provenance, runtime data, and scientific parameters are simplified and expressed.     

Valproate Targets Mammalian Gastrulation Impairing Neural Tissue Differentiation and Development of the Placental Source In Vitro

The teratogenic activity of valproate (VPA), an antiepileptic and an inhibitor of histone deacetylase (HDACi), is dose-dependent in humans. Previous results showed that VPA impairs in vitro development and neural differentiation of the gastrulating embryo proper. We aimed to investigate the impact of a lower VPA dose in vitro and whether this effect is retained in transplants in vivo. Rat embryos proper (E9.5) and ectoplacental cones were separately cultivated at the air-liquid interface with or without 1 mM VPA. Embryos were additionally cultivated with HDACi Trichostatin A (TSA), while some cultures were syngeneically transplanted under the kidney capsule for 14 days. Embryos were subjected to routine histology, immunohistochemistry, Western blotting and pyrosequencing. The overall growth of VPA-treated embryos in vitro was significantly impaired. However, no differences in the apoptosis or proliferation index were found. Incidence of the neural tissue was lower in VPA-treated embryos than in controls. TSA also impaired growth and neural differentiation in vitro. VPA-treated embryos and their subsequent transplants expressed a marker of undifferentiated neural cells compared to controls where neural differentiation markers were expressed. VPA increased the acetylation of histones. Our results point to gastrulation as a sensitive period for neurodevelopmental impairment caused by VPA.     

The dynamic capabilities perspective of strategic management: a co-citation analysis

Scientometrics - Dynamic capabilities currently emerge as a vibrant field of study within the theoretical framework based on resource and strategic management. To this end, and as a complex field...     

Influence of pineapple,apple and melon by‐products on cookies: physicochemical and sensory aspects

Physicochemical and sensory effects were investigated regarding the partial substitution of wheat flour in cookies with flours made of pineapple, apple and melon by‐products, in the concentrations 5%, 10% and 15%. Cookies with 15% of melon flour were prominent in relation to the nutritional aspects, especially about the contents of fibres (4.67–6.46%) and ash (1.74–2.25%). The use of these by‐products resulted in slightly darker cookies, with variations in diameter and in the expansion factor. There was a positive influence of the use of the pineapple by‐product concerning consumers' preference. Additionally, the cookies with 15% of pineapple by‐product presented the highest acceptance rate (97%) and buying intention (53%). Therefore, the use of fruit by‐products in the development of cookies is a viable alternative which can be explored for nutritional, technological and sensory purposes by the food industry.