Structural Data on the Periplasmic Aldehyde Oxidoreductase PaoABC from Escherichia coli: SAXS and Preliminary X-ray Crystallography Analysis

The periplasmic aldehyde oxidoreductase PaoABC from Escherichia coli is a molybdenum enzyme involved in detoxification of aldehydes in the cell. It is an example of an αβγ heterotrimeric enzyme of the xanthine oxidase family of enzymes which does not dimerize via its molybdenum cofactor binding domain. In order to structurally characterize PaoABC, X-ray crystallography and small angle X-ray scattering (SAXS) have been carried out. The protein crystallizes in the presence of 20% (w/v) polyethylene glycol 3350 using the hanging-drop vapour diffusion method. Although crystals were initially twinned, several experiments were done to overcome twinning and lowering the crystallization temperature (293 K to 277 K) was the solution to the problem. The non-twinned crystals used to solve the structure diffract X-rays to beyond 1.80 Å and belong to the C2 space group, with cell parameters a = 109.42 Å, b = 78.08 Å, c = 151.77 Å, β = 99.77°, and one molecule in the asymmetric unit. A molecular replacement solution was found for each subunit separately, using several proteins as search models. SAXS data of PaoABC were also collected showing that, in solution, the protein is also an αβγ heterotrimer.     

Betulinic Acid in Complex with a Gamma-Cyclodextrin Derivative Decreases Proliferation and in Vivo Tumor Development of Non-Metastatic and Metastatic B164A5 Cells

Betulinic acid, a very promising anti-melanoma agent, has very low water solubility that causes low bioavailability. To overcome this inconvenience, a highly water-soluble cyclodextrin was used (octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonic acid)]-γ-cyclodextrin). The complex was physico-chemically analyzed using differential scanning calorimetry (DSC), X-ray and scanning electron microscopy (SEM) methods and then in vitro tested for its antiproliferative activity by the MTT assay and by cell cycle analysis. Finally, the complex was tested in vivo using an animal model of murine melanoma developed in C57BL/6J mice, where it caused a reduction in tumor volume and weight. The study revealed the beneficial influence of betulinic acid inclusion into the cyclodextrin in terms of antiproliferative activity and in vivo tumor development.     

A framework for increasing the value of predictive data-driven models by enriching problem domain characterization with novel features

The need to leverage knowledge through data mining has driven enterprises in a demand for more data. However, there is a gap between the availability of data and the application of extracted knowledge for improving decision support. In fact, more data do not necessarily imply better predictive data-driven marketing models, since it is often the case that the problem domain requires a deeper characterization. Aiming at such characterization, we propose a framework drawn on three feature selection strategies, where the goal is to unveil novel features that can effectively increase the value of data by providing a richer characterization of the problem domain. Such strategies involve encompassing context (e.g., social and economic variables), evaluating past history, and disaggregate the main problem into smaller but interesting subproblems. The framework is evaluated through an empirical analysis for a real bank telemarketing application, with the results proving the benefits of such approach, as the area under the receiver operating characteristic curve increased with each stage, improving previous model in terms of predictive performance.

     

Modeling the efficacy of persuasive strategies for different gamer types in serious games for health

Persuasive games for health are designed to alter human behavior or attitude using various Persuasive Technology (PT) strategies. Recent years have witnessed an increasing number of such games, which treat players as a monolithic group by adopting a one-size-fits-all design approach. Studies of gameplay motivation have shown that this is a bad approach because a motivational approach that works for one individual may actually demotivate behavior in others. In an attempt to resolve this weakness, we conducted a large-scale study on 1,108 gamers to examine the persuasiveness of ten PT strategies that are commonly employed in persuasive game design, and the receptiveness of seven gamer personalities (gamer types identified by BrianHex) to the ten PT strategies. We developed models showing the receptiveness of the gamer types to the PT strategies and created persuasive profiles, which are lists of strategies that can be employed to motivate behavior for each gamer type. We then explored the differences between the models and, based on the results, proposed two approaches for data-driven persuasive game design. The first is the one-size-fits-all approach that will motivate a majority of gamers, while not demotivating any player. The second is the personalized approach that will best persuade a particular type of gamer. We also compiled a list of the best and the worst strategies for each gamer type. Finally, to bridge the gap between game design and PT researchers, we map common game mechanics to the persuasive system design strategies.     

Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.     

Universities of the Kyrgyz Republic on the Web: accessibility and usability

Universal Access in the Information Society - Today the Internet is the easiest way to find information about any kind of organization, and the first impression about an organization is almost...     

Hyperbaric storage at and above room temperature of a highly perishable food

Hyperbaric storage at naturally variable room temperature (RT) conditions (18–21 °C) and above (30 °C) was evaluated as a possible new food preservation method, regardless of temperature. Preservation of watermelon juice (used as a case study of a highly perishable food) at RT and 5 °C at atmospheric pressure was compared to preservation under 100 MPa at RT. After 8 h of hyperbaric storage at 100 MPa, the initial microbial loads of the watermelon juice were reduced by 1 log unit for total aerobic mesophiles, and 1–2 log units for Enterobacteriaceae and yeasts and moulds, to levels of about 3 log units for the former and below the detection limit for the latter, and remained thereafter unchanged up to 60 h. Similar results were obtained at 30 °C at 100 MPa after 8 h. At atmospheric pressure at RT (24 h) and 30 °C (8 h), microbial levels were already above quantification limits and unacceptable for consumption. Furthermore, pressure attenuated the increase in titratable acidity verified at atmospheric pressure, but caused higher colour changes, especially a higher lightness and a lower browning degree. Post-hyperbaric storage at 5 °C revealed an extended shelf life, as an additional benefit of hyperbaric storage. These results show that hyperbaric storage is a very promising food preservation methodology.