Overcoming original antigenic sin to generate new CD8 T cell IFN-gamma responses in an antigen-experienced host

The failure to mount effective immunity to virus variants in a previously virus-infected host is known as original antigenic sin. We have previously shown that prior immunity to a virus capsid protein inhibits induction by immunization of an IFN-gamma CD8(+) T cell response to an epitope linked to the capsid protein. We now demonstrate that capsid protein-primed CD4(+) T cells secrete IL-10 in response to capsid protein presented by dendritic cells, and deviate CD8+ T cells responding to a linked MHC class I-restricted epitope to reduce IFN-gamma production. Neutralizing IL-10 while delivering further linked epitope, either in vitro or in vivo, restores induction by immunization of an Ag-specific IFN-gamma response to the epitope. This finding demonstrates a strategy for overcoming inhibition of MHC class I epitopes upon immunization of a host already primed to Ag, which may facilitate immunotherapy for chronic viral infection or cancer.

The key role of CD40 ligand in overcoming tumor-induced dendritic cell dysfunction

Overcoming dendritic cell (DC) dysfunction is a prerequisite for successful active immunotherapy against breast cancer. CD40 ligand (CD40L), a key molecule in the interface between T-lymphocytes and DCs, seems to be instrumental in achieving that goal. Commenting on our data that CD40L protects circulating DCs from apoptosis induced by breast tumor products, Lenahan and Avigan highlighted the potential of CD40L for immunotherapy. We expand on that argument by pointing to additional findings that CD40L not only rescues genuine DCs but also functionally improves populations of immature antigen-presenting cells that fill the DC compartment in patients with breast cancer.

Overcoming the problem of loss-in-capacity of calcium oxide in CO2 capture

Calcium oxide has been identified to be one of the best candidates for CO2 capture in zero-emission power-generation systems. However, it suffers a well-known problem of loss-in-capacity (i.e., its capacity of CO2 capture decreases after it undergoes cycles of carbonation/decarbonation). This problem is a potential obstacle to the adoption of the new technologies. This paper proposes a method of fabricating a CaO-based adsorbent without the problem of loss-in-capacity. An adsorbent was fabricated using the method and tested on a thermogravimetric analyzer. It was shown that the sorbent attained a utilization efficiency of more than 90% after 9 cycles of carbonation/decarbonation.

Overcoming shadows in 3-source photometric stereo

Light occlusions are one of the most significant difficulties of photometric stereo methods. When three or more images are available without occlusion, the local surface orientation is overdetermined so that shape can be computed and the shadowed pixels can be discarded. In this paper, we look at the challenging case when only two images are available without occlusion, leading to a one degree of freedom ambiguity per pixel in the local orientation. We show that, in the presence of noise, integrability alone cannot resolve this ambiguity and reconstruct the geometry in the shadowed regions. As the problem is ill-posed in the presence of noise, we describe two regularization schemes that improve the numerical performance of the algorithm while preserving the data. Finally, the paper describes how this theory applies in the framework of color photometric stereo where one is restricted to only three images and light occlusions are common. Experiments on synthetic and real image sequences are presented.

Overcoming network overload and redundancy in inter-organizational networks:the roles of potential and latent ties

This paper builds on Granovetter's distinction between strong and weak ties [Granovetter, M. S. 1973. The strength of weak ties. Amer. J. Sociol. 78(6) 1360–1380] in order to respond to recent calls for a more dynamic and processual understanding of networks. The concepts of potential and latent tie are deductively identified, and their implications for understanding how and why networks emerge, evolve, and change are explored. A longitudinal empirical study conducted with companies operating in the European motorsport industry reveals that firms take strategic actions to search for potential ties and reactivate latent ties in order to solve problems of network redundancy and overload. Examples are given, and their characteristics are examined to provide theoretical elaboration of the relationship between the types of tie and network evolution. These conceptual and empirical insights move understanding of the managerial challenge of building effective networks beyond static structural contingency models of optimal network forms to highlight the processes and capabilities of dynamic relationship building and network development. In so doing, this paper highlights the interrelationship between search and redundancy and the scope for strategic action alongside path dependence and structural influences on network processes.

Overcoming barriers to membrane protein structure determination

After decades of slow progress, the pace of research on membrane protein structures is beginning to quicken thanks to various improvements in technology, including protein engineering and microfocus X-ray diffraction. Here we review these developments and, where possible, highlight generic new approaches to solving membrane protein structures based on recent technological advances. Rational approaches to overcoming the bottlenecks in the field are urgently required as membrane proteins, which typically comprise ~30% of the proteomes of organisms, are dramatically under-represented in the structural database of the Protein Data Bank.

Overcoming schema heterogeneity between linked semantic repositories to improve coreference resolution

Schema heterogeneity issues often represent an obstacle for discovering coreference links between individuals in semantic data repositories. In this paper we present an approach, which performs ontology schema matching in order to improve instance coreference resolution performance. A novel feature of the approach is its use of existing instance-level coreference links defined in third-party repositories as background knowledge for schema matching techniques. In our tests of this approach we obtained encouraging results, in particular, a substantial increase in recall in comparison with existing sets of coreference links.

Hidden in plain sight:low-literacy adults in a developed country overcoming social and educational challenges through mobile learning support tools

Illiteracy is often associated with people in developing countries. However, an estimated 50 % of adults in a developed country such as Canada lack the literacy skills required to cope with the challenges of today's society; for them, tasks such as reading, understanding, basic arithmetic, and using everyday items are a challenge. Many community-based organizations offer resources and support for these adults, yet overall functional literacy rates are not improving. This is due to a wide range of factors, such as poor retention of adult learners in literacy programs, obstacles in transferring the acquired skills from the classroom to the real life, personal attitudes toward learning, and the stigma of functional illiteracy. In our research we examined the opportunities afforded by personal mobile devices in providing learning and functional support to low-literacy adults. We present the findings of an exploratory study aimed at investigating the reception and adoption of a technological solution for adult learners. ALEX© is a mobile application designed for use both in the classroom and in daily life in order to help low-literacy adults become increasingly literate and independent. Such a solution complements literacy programs by increasing users' motivation and interest in learning, and raising their confidence levels both in their education pursuits and in facing the challenges of their daily lives. We also reflect on the challenges we faced in designing and conducting our research with two user groups (adults enrolled in literacy classes and in an essential skills program) and contrast the educational impact and attitudes toward such technology between these. Our conclusions present the lessons learned from our evaluations and the impact of the studies' specific challenges on the outcome and uptake of such mobile assistive technologies in providing practical support to low-literacy adults in conjunction with literacy and essential skills training. © 2013 Her Majesty the Queen in Right of Canada.

Overcoming bottlenecks in the membrane protein structural biology pipeline

Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future.

Overcoming Barriers to Restaurant Food Safety

Food safety is critical to the success of restaurants. Yet current methods of controling foodborne illness are inadequate, including time and temperature control, safe food handling procedures, good employee hygiene, cleaning and sanitizing techniques, and Hazard Analysis and Critical Control Points (HACCP) plan. Several barriers to food safety in restaurants are identified and recommendations for management are suggested.

Overcoming The Impotency Of Marketing

In his dialogue titled - Overcoming The Impotency Of Marketing - K. Michael Haywood, Assistant Professor, School of Hotel and Food Administration, University of Guelph, originally reveals: “Many accommodation businesses have discovered that their marketing activities are becoming increasingly impotent. To overcome this evolutionary stage in the life cycle of marketing, this article outlines six principles that will re-establish marketing's vitality.” “The opinion of general managers and senior marketing, financial, and food and beverage managers is that the marketing is not producing the results it once did and is not working as it should,” Haywood advises. Haywood points to price as the primary component hospitality managers use to favor/adjust their marketability. Although this is an effective tool, the practice can also erode profitability and margin he says. Haywood also points at recession as a major factor in exposing the failures of marketing plans. He adds that the hotel manager cannot afford to let this rationale go unchallenged; managers must take measures to mitigate circumstances that they might not have any control over. Managers must attempt to maintain profitability. “In many hotels, large corporate accounts or convention business generates a significant proportion of occupancy. Often these big buyers dictate their terms to the hotels, especially the price they are prepared to pay and the service they expect,” Haywood warns. This dynamic is just another significant pitfall that challenges marketing strategy. The savvy marketing technician must be aware of changes that occur in his or her marketplace, Haywood stresses. He offers three specific, real changes, which should be responded to. “To cope with the problems and uncertainties of the hotel business during the remainder of the decade, six components need to be developed if marketing impotency is to be overcome,” says Haywood in outlining his six-step approach to the problem. Additionally, forward thinking cannot be over-emphasized. “A high market share is helpful in general, but an even more crucial factor is careful consideration of the market sectors in which the company wants to operate,” your author advises. “Taking tactical initiatives is essential. Successful hotels act; unsuccessful ones react. The less successful marketing operations tend to be a hive of frantic activity. Fire-fighting is the normal way of life in such organizations, Haywood observes. “By contrast, successful firms plan and execute their tactical marketing activity with careful timing and precision so as to create the maximum impact,” he extends in describing his fruitful marketing arabesque.