Towards the in silico identification of class II restricted T-cell epitopes:a partial least squares iterative self-consistent algorithm for affinity prediction

Motivation: The immunogenicity of peptides depends on their ability to bind to MHC molecules. MHC binding affinity prediction methods can save significant amounts of experimental work. The class II MHC binding site is open at both ends, making epitope prediction difficult because of the multiple binding ability of long peptides. Results: An iterative self-consistent partial least squares (PLS)-based additive method was applied to a set of 66 pep- tides no longer than 16 amino acids, binding to DRB1*0401. A regression equation containing the quantitative contributions of the amino acids at each of the nine positions was generated. Its predictability was tested using two external test sets which gave r pred =0.593 and r pred=0.655, respectively. Furthermore, it was benchmarked using 25 known T-cell epitopes restricted by DRB1*0401 and we compared our results with four other online predictive methods. The additive method showed the best result finding 24 of the 25 T-cell epitopes. Availability: Peptides used in the study are available from http://www.jenner.ac.uk/JenPep. The PLS method is available commercially in the SYBYL molecular modelling software package. The final model for affinity prediction of peptides binding to DRB1*0401 molecule is available at http://www.jenner.ac.uk/MHCPred. Models developed for DRB1*0101 and DRB1*0701 also are available in MHC- Pred

Towards the Problems of an Evaluation of Data Uncertainty in Decision Support Systems

The question of forming aim-oriented description of an object domain of decision support process is outlined. Two main problems of an estimation and evaluation of data and knowledge uncertainty in decision support systems – straight and reverse, are formulated. Three conditions being the formalized criteria of aimoriented constructing of input, internal and output spaces of some decision support system are proposed. Definitions of appeared and hidden data uncertainties on some measuring scale are given.

Towards the Noosphere of Intangible (Esotericism from Materialistic Viewpoint)

Exploration of intangible world is under the serious influence of esotericism. Mystics, religions, unrestrained use of metaphors, fairy tales, gossips, unverified and uncertified “facts” – all this needs accurate well-disposed, but sound scientific consideration. Our society really needs new ideas, new approaches and new paradigms. Technological civilization becomes more and more complicated, risky and ecologically critical. The current level of AI research cannot guarantee successful solution of societal control and management. Besides, the human being itself practically did not change its mental and psychological abilities for many thousands years. We can lose control over our society and its technology, if we do not change cardinally ourselves. In this text, I tried to approach this problem – the problem of our noosphere from materialistic viewpoint.

Towards the Semiotics of Noosphere

Civilization has brought us into the noosphere world. Besides physical, around (and inside of) us exist and function also mental and cultural entities. It is impossible to perform now knowledge acquisition, knowledge base creation and organizational systems management without adequate consideration of object’s noosphere statuses. I tried here to clarify basic viewpoints concerning this issue, hoping that elaboration of common methodological foundations of semiotic modeling will be useful for developers and also for users of new generation automation systems.

A knowledge driven approach towards the validation of externally acquired traceability datasets in supply chain business processes

The sharing of near real-time traceability knowledge in supply chains plays a central role in coordinating business operations and is a key driver for their success. However before traceability datasets received from external partners can be integrated with datasets generated internally within an organisation, they need to be validated against information recorded for the physical goods received as well as against bespoke rules defined to ensure uniformity, consistency and completeness within the supply chain. In this paper, we present a knowledge driven framework for the runtime validation of critical constraints on incoming traceability datasets encapuslated as EPCIS event-based linked pedigrees. Our constraints are defined using SPARQL queries and SPIN rules. We present a novel validation architecture based on the integration of Apache Storm framework for real time, distributed computation with popular Semantic Web/Linked data libraries and exemplify our methodology on an abstraction of the pharmaceutical supply chain.

Towards the distributed core for ubiquitous superfast broadband optical access

In this paper, we describe recent architectural and technological advances of the end to end optical network architecture proposed by the DISCUS project (the DIStributed Core for unlimited bandwidth supply for all Users and Services). The two main targets of DISCUS are the principle of equivalence in the access and the reduction of optical-to-electronic conversions in the metro-core network. Technological advances and techno-economic evaluation of Long-Reach Passive Optical Networks (LR-PON), as well as the optimal metro-core node architecture and the required network control plane framework are reported. Network infrastructure sharing challenges are also discussed. © 2014 IEEE.

Towards the strategic adoption of Lean in aviation Maintenance Repair and Overhaul (MRO) industry:an empirical study into the industry's Lean status

Purpose - Despite many Maintenance Repair and Overhaul (MRO) organisations alluding their positive business performances to the adoption Lean initiatives, there is a paucity of direct literature that validates this assertion. Thus, the purpose of this paper is to study empirically via the use of an industry-wide survey to establish and extent of Lean adoption and to verify its suitability in mitigating prevalent MRO challenges. Design/methodology/approach - The empirical study contained in this paper is facilitated by an industry-wide survey to collect data from several firms across the MRO spectrum. The analysed responses from industry leaders, professionals and executives synthesised with existing literature was used in ascertaining the extent of Lean adoption within the operational framework of the industry. Findings - The empirical study helped in validating the suitability of Lean in MRO context. However, it was also observed that the focus of its application was skewed towards its production-orientated functions more than its service-orientated functions. Nonetheless, this paper presents results of the positive influence of Lean in MRO context. Research limitations/implications - This empirical study presented in this paper was carried out within a framework of key characteristics of operation. Although this approach is sufficient in assessing the industry's Lean status, further assessment can also be achieved within the context of relevant performance metrics which was not included in this paper. Practical implications - By exploring the industry's Lean status within the context of operational characteristics of operation, this study provides MRO practitioners with more awareness into some of the critical factors required for successful holistic Lean realisation. Social implications - The state-of-the-art of Lean within the aviation MRO context established through this research also contributes to the wider product-centric service environment by providing a platform that facilitates strategy development which ensures Lean success within this environment. Originality/value - Apart from validating the suitability of Lean in MRO contexts, by establishing the extent of Lean adoption within the context of the operational framework, this paper provides a clearer insight as to how successful Lean implementation can be achieved via a holistic implementation strategy balanced between the product-centric and service-centric aspects of the industry.

Towards the knowledge-based design of universal influenza epitope ensemble vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly-conserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes.

Towards the formation of a sustainable South Florida: An analysis of conflict resolution and consensus building in the South Florida Everglades Ecosystem Restoration Initiative

This dissertation examines the sociological process of conflict resolution and consensus building in South Florida Everglades Ecosystem Restoration through what I define as a Network Management Coordinative Interstitial Group (NetMIG). The process of conflict resolution can be summarized as the participation of interested and affected parties (stakeholders) in a forum of negotiation. I study the case of the Governor's Commission for a Sustainable South Florida (GCSSF) that was established to reduce social conflict. Such conflict originated from environmental disputes about the Everglades and was manifested in the form of gridlock among regulatory (government) agencies, Indian tribes, as well as agricultural, environmental conservationist and urban development interests. The purpose of the participatory forum is to reduce conflicts of interest and to achieve consensus, with the ultimate goal of restoration of the original Everglades ecosystem, while cultivating the economic and cultural bases of the communities in the area. Further, the forum aim to formulate consensus through envisioning a common sustainable community by providing means to achieve a balance between human and natural systems. ^ Data were gathered using participant observation and document analysis techniques to conduct a theoretically based analysis of the role of the Network Management Coordinative Interstitial Group (NetMIG). I use conflict resolution theory, environmental conflict theory, stakeholder analysis, systems theory, differentiation and social change theory, and strategic management and planning theory. ^ The purpose of this study is to substantiate the role of the Governor's Commission for a Sustainable South Florida (GCSSF) as a consortium of organizations in an effort to resolve conflict rather than an ethnographic study of this organization. Environmental restoration of the Everglades is a vehicle for recognizing the significance of a Network Management Coordinative Interstitial Group (NetMIG), namely the Governor's Commission for a Sustainable South Florida (GCSSF), as a structural mechanism for stakeholder participation in the process of social conflict resolution through the creation of new cultural paradigms for a sustainable community. ^

An assessment of computer usage within the Bahamian public school system and recommended guidelines towards the development of a strategic national computer plan

Computers have dramatically changed the way we live, conduct business, and deliver education. They have infiltrated the Bahamian public school system to the extent that many educators now feel the need for a national plan. The development of such a plan is a challenging undertaking, especially in developing countries where physical, financial, and human resources are scarce. This study assessed the situation with regard to computers within the Bahamian public school system, and provided recommended guidelines to the Bahamian government based on the results of a survey, the body of knowledge about trends in computer usage in schools, and the country's needs. ^ This was a descriptive study for which an extensive review of literature in areas of computer hardware, software, teacher training, research, curriculum, support services and local context variables was undertaken. One objective of the study was to establish what should or could be relative to the state-of-the-art in educational computing. A survey was conducted involving 201 teachers and 51 school administrators from 60 randomly selected Bahamian public schools. A random stratified cluster sampling technique was used. ^ This study used both quantitative and qualitative research methodologies. Quantitative methods were used to summarize the data about numbers and types of computers, categories of software available, peripheral equipment, and related topics through the use of forced-choice questions in a survey instrument. Results of these were displayed in tables and charts. Qualitative methods, data synthesis and content analysis, were used to analyze the non-numeric data obtained from open-ended questions on teachers' and school administrators' questionnaires, such as those regarding teachers' perceptions and attitudes about computers and their use in classrooms. Also, interpretative methodologies were used to analyze the qualitative results of several interviews conducted with senior public school system's officials. Content analysis was used to gather data from the literature on topics pertaining to the study. ^ Based on the literature review and the data gathered for this study a number of recommendations are presented. These recommendations may be used by the government of the Commonwealth of The Bahamas to establish policies with regard to the use of computers within the public school system. ^

Attitudes towards the marine environment and implications for marine resource management in Seward, Alaska

This research, conducted in 2006-2008, examines the ways in which various groups involved with the marine resources of Seward, Alaska construct attitudes towards the environment. Participant observation and semi-structured interviews are used to assess how commercial halibut fishers, tour boat operators, local residents and government officials understand the marine environment based on their previous experiences. This study also explores how ideologies relate to the current practices of each group. Two theories orient the analyses: The first, cultural modeling provided a theoretical and methodological framework for pursuing a more comprehensive analysis of resource management. The second, Theory of Reasoned Action (Ajzen and Fishbein 1980), guided the analysis of the ways in which each participant’s ideology towards the marine environment relates to their practice. Aside from contributing to a better understanding of a coastal community’s ideologies and practices, this dissertation sought to better understand the role of ecological ideologies and behaviors in fisheries management. The research illustrates certain domains where ideologies and practices concerning Pacific halibut and the marine environment differ among commercial fishers, government, and management officials, tour boat operators and residents of Seward, AK. These differences offer insights into how future collaborative efforts between government officials, managers and local marine resource users might better incorporate local ideology into management, and provide ecological information to local marine resource users in culturally appropriate ways.

New organogermanium substrates for palladium-catalyzed cross-coupling reactions. Application of organogermanes towards the synthesis of carbon-5 modified uridine analogues

The diverse biological properties exhibited by uridine analogues modified at carbon-5 of the uracil base have attracted special interest to the development of efficient methodologies for their synthesis. This study aimed to evaluate the possible application of vinyl tris(trimethylsilyl)germanes in the synthesis of conjugated 5-modified uridine analogues via Pd-catalyzed cross-coupling reactions. The stereoselective synthesis of 5-[(2-tris(trimethylsilyl)germyl)ethenyl]uridine derivatives was achieved by the radical-mediated hydrogermylation of the protected 5-alkynyluridine precursors with tris(trimethylsilyl)germane [(TMS)3GeH]. The hydrogermylation with Ph3GeH afforded in addition to the expected 5-vinylgermane, novel 5-(2-triphenylgermyl)acetyl derivatives. Also, the treatment with Me3GeH provided access to 5-vinylgermane uridine analogues with potential biological applications. Since the Pd-catalyzed cross-coupling of organogermanes has received much less attention than the couplings involving organostannanes and organosilanes, we were prompted to develop novel organogermane precursors suitable for transfer of aryl and/or alkenyl groups. The allyl(phenyl)germanes were found to transfer allyl groups to aryl iodides in the presence of sodium hydroxide or tetrabutylammonium fluoride (TBAF) via a Heck arylation mechanism. On the other hand, the treatment of allyl(phenyl)germanes with tetracyanoethylene (TCNE) effectively cleaved the Ge-C(allyl) bonds and promoted the transfer of the phenyl groups upon fluoride activation in toluene. It was discovered that the trichlorophenyl,- dichlorodiphenyl,- and chlorotriphenylgermanes undergo Pd-catalyzed cross-couplings with aryl bromides and iodides in the presence of TBAF in toluene with addition of the measured amount of water. One chloride ligand on the Ge center allows efficient activation by fluoride to promote transfer of one, two or three phenyl groups from the organogermane precursors. The methodology shows that organogermanes can render a coupling efficiency comparable to the more established stannane and silane counterparts. Our coupling methodology (TBAF/moist toluene) was also found to promote the transfer of multiple phenyl groups from analogous chloro(phenyl)silanes and stannanes.