Anatomical physiological and biochemical processes involved in grapevine rootstock drought tolerance

In order to explore the drought resistance mechanism of grape rootstocks, two grape rootstock species, '1103P' (a drought-tolerant rootstock) and '101-14M' (drought-sensitive), were treated with moderate water deficit (field capacity of 45-50 %). Throughout the experimental period, the leaves of '1103P' showed a higher stomatal conductance (gs), relative water content and photosynthetic rate (Pn) than '101-14M', indicating '1103P' was more resistant to tolerant than '101-14M'. We propose that '1103P' could prevent water loss from leaves under drought conditions based on the discoveries that '1103P' had higher leaf phytohormone abscisic acid (ABA) content and leaf cuticular wax content, and smaller stomata aperture than those of '101-14M'. Additionally, the activities of H2O2-scavenging enzymes in leaves of '1103P' were higher than those of '101-14M' under drought conditions, indicating the lipid peroxidation induced by H2O2 of '1103P' was less serious than that of '101-14M'. Therefore, better water-saving and higher reactive oxygen species (ROS) scavenging abilities contributed together to stronger drought resistance of '1103P' than '101-14M'

A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal–organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.</p

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

Modeling and Verification of Adaptive Navigation in Web Applications

The navigation of a web application is the possible sequences of web pages a user can visit. In the simplest case the next page is determined by the current page and the action (e.g. link, button) selected by the user. However, many web applications now incorporate adaptive navigation, where the next page also depends on the user’s mode, for example whether they are a customer or an administrator, or depends on what pages the user has visited previously. Navigation models are useful for clarifying requirements and specifying implementation behavior. When a model is formal, it can also be used to generate design or implementation artifacts, and can be verified for properties such as broken links or length of navigation path. These uses are all important for the case of simple navigation, but even more important for adaptive navigation because of the added complexity. However, none of the current formal approaches can support adaptive navigation. In this paper we present an approach that uses Statecharts to formally model adaptive navigation, and show how important properties of a navigation model are verified using existing model-checking tools. We summarize the kinds of properties that can be checked with such a model, and describe how to use the Symbolic Model Verifier (SMV) tool to perform the verification. Finally, we use the Blockbuster ® web site as a case study to demonstrate how our approach can uncover navigation problems that arise when new requirements are imposed

Modeling and Verification of Adaptive Navigation in Web Applications

The navigation of a web application is the possible sequences of web pages a user can visit. In the simplest case the next page is determined by the current page and the action (e.g. link, button) selected by the user. However, many web applications now incorporate adaptive navigation, where the next page also depends on the user’s mode, for example whether they are a customer or an administrator, or depends on what pages the user has visited previously. Navigation models are useful for clarifying requirements and specifying implementation behavior. When a model is formal, it can also be used to generate design or implementation artifacts, and can be verified for properties such as broken links or length of navigation path. These uses are all important for the case of simple navigation, but even more important for adaptive navigation because of the added complexity. However, none of the current formal approaches can support adaptive navigation. In this paper we present an approach that uses Statecharts to formally model adaptive navigation, and show how important properties of a navigation model are verified using existing model-checking tools. We summarize the kinds of properties that can be checked with such a model, and describe how to use the Symbolic Model Verifier (SMV) tool to perform the verification. Finally, we use the Blockbuster ® web site as a case study to demonstrate how our approach can uncover navigation problems that arise when new requirements are imposed

Loss of CO2 sensing by the olfactory system of CNGA3 knockout mice

Atmospheric CO2 can signal the presence of food, predators or environmental stress and trigger stereotypical behaviors in both vertebrates and invertebrates. Recent studies have shown that the necklace olfactory system in mice sensitively detects CO2 in the air. Olfactory CO2 neurons are believed to rely on cyclic guanosine monophosphate (cGMP) as the key second messenger; however, the specific ion channel underlying CO­2 responses remains unclear. Here we show that CO2-evoked neuronal and behavioral responses require cyclic nucleotide-gated (CNG) channels consisting of the CNGA3 subunit. Through Ca2+-imaging, we found that CO2-triggered Ca2+ influx was abolished in necklace olfactory sensory neurons (OSNs) of CNGA3-knockout mice. Olfactory detection tests using a Go/No-go paradigm showed that these knockout mice failed to detect 0.5% CO2. Thus, sensitive detection of atmospheric CO2 depends on the function of CNG channels consisting of the CNGA3 subunit in necklace OSNs. These data support the important role of the necklace olfactory system in CO2 sensing and extend our understanding of the signal transduction pathway mediating CO2 detection in mammals [Current Zoology 56 (6): 793–799, 2010]

Separation of Navigation Routing Code in J2EE Web Applications

Abstract. The navigation routing code of a web application is the part of the code involved in routing a request from a web page through the appropriate components on the server, typically ending with the display of a response page. Common maintenance activities are to change the sequence of pages or the processing for a page, and for these activities the navigation routing code must be located, understood, and possibly modified. But in J2EE applications this code is spread among a number of components, making maintenance costly. We describe an approach for separating this navigation routing code, using either Aspect Oriented Programming (AOP) or conventional OO techniques. We demonstrate how this improves maintainability by converting three exemplar applications from Sun and Oracle, with a 4- to 11-fold reduction in the number of files containing navigation routing code and in the lines of code in these files.