GRID and docking analyses reveal a molecular basis for flavonoid inhibition of src-family kinase activity

Flavonoids reduce cardiovascular disease risk through anti-inflammatory, anti-coagulant and anti-platelet actions. One key flavonoid inhibitory mechanism is blocking kinase activity that drives these processes. Flavonoids attenuate activities of kinases including phosphoinositide-3-kinase (PI3K), Fyn, Lyn, Src, Syk, PKC, PIM1/2, ERK, JNK, and PKA. X-ray crystallographic analyses of kinase-flavonoid complexes show that flavonoid ring systems and their hydroxyl substitutions are important structural features for their binding to kinases. A clearer understanding of structural interactions of flavonoids with kinases is necessary to allow construction of more potent and selective counterparts. We examined flavonoid (quercetin, apigenin and catechin) interactions with Src-family kinases (Lyn, Fyn and Hck) applying the Sybyl docking algorithm and GRID. A homology model (Lyn) was used in our analyses to demonstrate that high quality predicted kinase structures are suitable for flavonoid computational studies. Our docking results revealed potential hydrogen bond contacts between flavonoid hydroxyls and kinase catalytic site residues. Identification of plausible contacts indicated that quercetin formed the most energetically stable interactions, apigenin lacked hydroxyl groups necessary for important contacts, and the non-planar structure of catechin could not support predicted hydrogen bonding patterns. GRID analysis using a hydroxyl functional group supported docking results. Based on these findings, we predicted that quercetin would inhibit activities of Src-family kinases with greater potency than apigenin and catechin. We validated this prediction using in vitro kinase assays. We conclude that our study can be used as a basis to construct virtual flavonoid interaction libraries to guide drug discovery using these compounds as molecular templates.

Computing the Cassels–Tate pairing on the 3-Selmer group of an elliptic curve

We extend the method of Cassels for computing the Cassels-Tate pairing on the 2-Selmer group of an elliptic curve, to the case of 3-Selmer groups. This requires significant modifications to both the local and global parts of the calculation. Our method is practical in sufficiently small examples, and can be used to improve the upper bound for the rank of an elliptic curve obtained by 3-descent.

Exploring smart grid possibilities: a complex systems modelling approach

Smart grid research has tended to be compartmentalised, with notable contributions from economics, electrical engineering and science and technology studies. However, there is an acknowledged and growing need for an integrated systems approach to the evaluation of smart grid initiatives. The capacity to simulate and explore smart grid possibilities on various scales is key to such an integrated approach but existing models – even if multidisciplinary – tend to have a limited focus. This paper describes an innovative and flexible framework that has been developed to facilitate the simulation of various smart grid scenarios and the interconnected social, technical and economic networks from a complex systems perspective. The architecture is described and related to realised examples of its use, both to model the electricity system as it is today and to model futures that have been envisioned in the literature. Potential future applications of the framework are explored, along with its utility as an analytic and decision support tool for smart grid stakeholders.

Bayesian analysis of uncertainty in the GlobCover 2009 land cover product at climate model grid scale

Land cover data derived from satellites are commonly used to prescribe inputs to models of the land surface. Since such data inevitably contains errors, quantifying how uncertainties in the data affect a model’s output is important. To do so, a spatial distribution of possible land cover values is required to propagate through the model’s simulation. However, at large scales, such as those required for climate models, such spatial modelling can be difficult. Also, computer models often require land cover proportions at sites larger than the original map scale as inputs, and it is the uncertainty in these proportions that this article discusses. This paper describes a Monte Carlo sampling scheme that generates realisations of land cover proportions from the posterior distribution as implied by a Bayesian analysis that combines spatial information in the land cover map and its associated confusion matrix. The technique is computationally simple and has been applied previously to the Land Cover Map 2000 for the region of England and Wales. This article demonstrates the ability of the technique to scale up to large (global) satellite derived land cover maps and reports its application to the GlobCover 2009 data product. The results show that, in general, the GlobCover data possesses only small biases, with the largest belonging to non–vegetated surfaces. In vegetated surfaces, the most prominent area of uncertainty is Southern Africa, which represents a complex heterogeneous landscape. It is also clear from this study that greater resources need to be devoted to the construction of comprehensive confusion matrices.

Estrogen receptor: Structural differences and potential implications on selectivity examined by the GRID/CPCA approach

Selective Estrogen Receptor Modulators ( SERMs) have been developed, but the selectivity towards the subtypes ( ER or ER is not well understood. Based on three-dimensional structural properties of ligand binding domains, a model that takes into account this aspect was developed via molecular interaction fields and consensus principal component analysis (GRID/CPCA).

Energy Storage for a Grid-Connected PV-System: A Feasibility Study

The work presented in this thesis concerns the dimensioning of an Energy Storage System (ESS) which will be used as an energy buffer for a grid-connected PV plant. This ESS should help managing the PV plant to inject electricity into the grid according to the requirements of the grid System Operator. It is desired to obtain a final production not below 1300kWh/kWp with a maximum ESS budget of 0.9€/Wp. The PV plant will be sited in Martinique Island and connected to the main grid. This grid is a small one where the perturbations due clouds in the PV generation are not negligible anymore. A software simulation tool, incorporating a model for the PV-plant production, the ESS and the required injection pattern of electricity into the grid has been developed in MS Excel. This tool has been used to optimize the relevant parameters defining the ESS so that the feed-in of electricity into the grid can be controlled to fulfill the conditions given by the System Operator. The inputs used for this simulation tool are, besides the conditions given by the System Operator on the allowed injection pattern, the production data from a similar PV-plant in a close-by location, and variables for defining the ESS. The PV production data used is from a site with similar climate and weather conditions as for the site on the Martinique Island and hence gives information on the short term insolation variations as well as expected annual electricity production. The ESS capacity and the injected electric energy will be the main figures to compare while doing an economic study of the whole plant. Hence, the Net Present Value, Benefit to Cost method and Pay-back period studies are carried on as dependent of the ESS capacity. The conclusion of this work is that it is possible to obtain the requested injection pattern by using an ESS. The design of the ESS can be made within an acceptable budget. The capacity of ESS to link with the PV system depends on the priorities of the final output characteristics, and it also depends on which economic parameter that is chosen as a priority.

Cloud computing - Moving to the cloud

Cloud computing innebär användning av datorresurser som är tillgängliga via ett nätverk, oftast Internet och är ett område som har vuxit fram i snabb takt under de senaste åren. Allt fler företag migrerar hela eller delar av sin verksamhet till molnet. Sogeti i Borlänge har behov av att migrera sina utvecklingsmiljöer till en molntjänst då drift och underhåll av dessa är kostsamma och tidsödande. Som Microsoftpartners vill Sogeti använda Microsoft tjänst för cloud computing, Windows Azure, för detta syfte. Migration till molnet är ett nytt område för Sogeti och de har inga beskrivningar för hur en sådan process går till. Vårt uppdrag var att utveckla ett tillvägagångssätt för migration av en IT-lösning till molnet. En del av uppdraget blev då att kartlägga cloud computing, dess beståndsdelar samt vilka för- och nackdelar som finns, vilket har gjort att vi har fått grundläggande kunskap i ämnet. För att utveckla ett tillvägagångssätt för migration har vi utfört flera migrationer av virtuella maskiner till Windows Azure och utifrån dessa migrationer, litteraturstudier och intervjuer dragit slutsatser som mynnat ut i ett generellt tillvägagångssätt för migration till molnet. Resultatet har visat att det är svårt att göra en generell men samtidigt detaljerad beskrivning över ett tillvägagångssätt för migration, då scenariot ser olika ut beroende på vad som ska migreras och vilken typ av molntjänst som används. Vi har dock utifrån våra erfarenheter från våra migrationer, tillsammans med litteraturstudier, dokumentstudier och intervjuer lyft vår kunskap till en generell nivå. Från denna kunskap har vi sammanställt ett generellt tillvägagångssätt med större fokus på de förberedande aktiviteter som en organisation bör genomföra innan migration. Våra studier har även resulterat i en fördjupad beskrivning av cloud computing. I vår studie har vi inte sett att någon tidigare har beskrivit kritiska framgångsfaktorer i samband med cloud computing. I vårt empiriska arbete har vi dock identifierat tre kritiska framgångsfaktorer för cloud computing och i och med detta täckt upp en del av kunskapsgapet där emellan.

Ubiquitous computing in education : a SWOT analysis by students and teachers

Learning from anywhere anytime is a contemporary phenomenon in the field of education that is thought to be flexible, time and cost saving. The phenomenon is evident in the way computer technology mediates knowledge processes among learners. Computer technology is however, in some instances, faulted. There are studies that highlight drawbacks of computer technology use in learning. In this study we aimed at conducting a SWOT analysis on ubiquitous computing and computer-mediated social interaction and their affect on education. Students and teachers were interviewed on the mentioned concepts using focus group interviews. Our contribution in this study is, identifying what teachers and students perceive to be the strength, weaknesses, opportunities and threats of ubiquitous computing and computer-mediated social interaction in education. We also relate the findings with literature and present a common understanding on the SWOT of these concepts. Results show positive perceptions. Respondents revealed that ubiquitous computing and computer-mediated social interaction are important in their education due to advantages such as flexibility, efficiency in terms of cost and time, ability to acquire computer skills. Nevertheless disadvantages where also mentioned for example health effects, privacy and security issues, noise in the learning environment, to mention but a few. This paper gives suggestions on how to overcome threats mentioned.

Soft computing in biometrics : a pragmatic appraisal

The ever increasing spurt in digital crimes such as image manipulation, image tampering, signature forgery, image forgery, illegal transaction, etc. have hard pressed the demand to combat these forms of criminal activities. In this direction, biometrics - the computer-based validation of a persons' identity is becoming more and more essential particularly for high security systems. The essence of biometrics is the measurement of person’s physiological or behavioral characteristics, it enables authentication of a person’s identity. Biometric-based authentication is also becoming increasingly important in computer-based applications because the amount of sensitive data stored in such systems is growing. The new demands of biometric systems are robustness, high recognition rates, capability to handle imprecision, uncertainties of non-statistical kind and magnanimous flexibility. It is exactly here that, the role of soft computing techniques comes to play. The main aim of this write-up is to present a pragmatic view on applications of soft computing techniques in biometrics and to analyze its impact. It is found that soft computing has already made inroads in terms of individual methods or in combination. Applications of varieties of neural networks top the list followed by fuzzy logic and evolutionary algorithms. In a nutshell, the soft computing paradigms are used for biometric tasks such as feature extraction, dimensionality reduction, pattern identification, pattern mapping and the like.