MHC class II binding prediction:a little help from a friend

Vaccines are the greatest single instrument of prophylaxis against infectious diseases, with immeasurable benefits to human wellbeing. The accurate and reliable prediction of peptide-MHC binding is fundamental to the robust identification of T-cell epitopes and thus the successful design of peptide- and protein-based vaccines. The prediction of MHC class II peptide binding has hitherto proved recalcitrant and refractory. Here we illustrate the utility of existing computational tools for in silico prediction of peptides binding to class II MHCs. Most of the methods, tested in the present study, detect more than the half of the true binders in the top 5% of all possible nonamers generated from one protein. This number increases in the top 10% and 15% and then does not change significantly. For the top 15% the identified binders approach 86%. In terms of lab work this means 85% less expenditure on materials, labour and time. We show that while existing caveats are well founded, nonetheless use of computational models of class II binding can still offer viable help to the work of the immunologist and vaccinologist.

Is a little sunshine all we need? On the impact of sunshine regulation on profits, productivity and prices in the Dutch drinking water sector

This paper analyzes the performance of Dutch drinking water utilities before and after the introduction of sunshine regulation, which involves publication of the performance of utilities but no formal price regulation. By decomposing profit change into its economic drivers, our results suggest that, in the Dutch political and institutional context, sunshine regulation was effective in improving the productivity of publicly organised services. Nevertheless, while sunshine regulation did bring about a moderate reduction in water prices, sustained and substantial economic profits suggest that it may not have the potential to fully align output prices with economic costs in the long run. In methodological terms, the DEA based profit decomposition is extended to robust and conditional non-parametric efficiency measures, so as to account better for both uncertainty and differences in operating environment between utilities.

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo's potential, affecting adult health

Periconceptional environment may influence embryo development, ultimately affecting adult health. Here, we review the rodent model of maternal low-protein diet specifically during the preimplantation period (Emb-LPD) with normal nutrition during subsequent gestation and postnatally. This model, studied mainly in the mouse, leads to cardiovascular, metabolic and behavioural disease in adult offspring, with females more susceptible. We evaluate the sequence of events from diet administration that may lead to adult disease. Emb-LPD changes maternal serum and/or uterine fluid metabolite composition, notably with reduced insulin and branched-chain amino acids. This is sensed by blastocysts through reduced mammalian target of rapamycin complex 1 signalling. Embryos respond by permanently changing the pattern of development of their extra-embryonic lineages, trophectoderm and primitive endoderm, to enhance maternal nutrient retrieval during subsequent gestation. These compensatory changes include stimulation in proliferation, endocytosis and cellular motility, and epigenetic mechanisms underlying them are being identified. Collectively, these responses act to protect fetal growth and likely contribute to offspring competitive fitness. However, the resulting growth adversely affects long-term health because perinatal weight positively correlates with adult disease risk. We argue that periconception environmental responses reflect developmental plasticity and 'decisions' made by embryos to optimise their own development, but with lasting consequences.

Little G. T. for lp-lattice summing operators

2000 Mathematics Subject Classification: 46B28, 47D15.

"It's so little money you could make as much at home" - options for work in an impoverished rural region of high unemployment.

Hungary has a higher unemployment rate than the member states of the European Union and even most former socialist countries. This rate for 15-64 year-olds has been around 56% since 1999, as against 66% in the European Union (OECD Employment Database). There is also a high degree of regional unevenness within the country. The situation is worst in North Hungary, an area of multiple economic and social deprivations. Several pieces of research have analysed the causes of long-term unemployment and have highlighted the main social, geographical and institutional factors behind it. People of low educational attainment who live in small villages and members of the Roma minority are particularly likely to have been without jobs for a long time.

Lokális energiamódszer kicsi rendben gerjesztett Liénard-egyenletekre (Local energy method for little order forced equations)

Az x''+f(x) x'+g(x) = 0 alakú Liénard-típusú differenciálegyenlet központi szerepet játszik az üzleti ciklusok Káldor-Kalecki-féle [3,4] és Goodwin-féle [2] modelljeiben, sőt egy a munkanélküliség és vállalkozás-ösztönzések ciklikus változásait leíró újabb modellben [1] is. De ugyanez a nemlineáris egyenlettípus a gerjesztett ingák és elektromos rezgőkörök elméletét is felöleli [5]. Az ezzel kapcsolatos irodalom nagyrészt a határciklusok létezését vizsgálja (pl. [5]), pedig az alapvető stabilitási kérdések jóval áttekinthetőbb módon kezelhetők, s a kapott eredmények közvetve a határciklusok létezésének feltételeit is sokkal jobban be tudják határolni. Jelen dolgozatban az egyváltozós analízis hatékony nyelvezetével olyan egyszerűen megfogalmazható eredményekhez jutunk, amelyek képesek kitágítani az üzleti és más közgazdasági ciklusok modelljeinek kereteit, illetve pl. az [1]-beli modellhez újabb szemléltető speciális eseteket is nyerünk. ____ The Liénard type differential equation of the form x00 + f(x) ¢ x0 + g(x) = 0 has a central role in business cycle models by Káldor [3], Kalecki [4] and Goodwin [2], moreover in a new model describing the cyclical behavior of unemployment and entrepreneurship [1]. The same type of nonlinear equation explains the features of forced pendulums and electric circuits [5]. The related literature discusses mainly the existence of limit cycles, although the fundamental stability questions of this topic can be managed much more easily. The achieved results also outline the conditions for the existence of limit cycles. In this work, by the effective language of real valued analysis, we obtain easy-formulated results which may broaden the frames of economic and business cycle models, moreover we may gain new illustrative particular cases for e.g., [1].

Landscape of fear: A social history of the missile during the early years of the Cold War, 1950–1965

The missile's significance has been central to national security since the Soviet launching of Sputnik, and became increasingly important throughout the years of the Cold War. Much has been written about missile technology, but little has been written about how the development and deployment of this weapon affected Americans. The missile was developed to both deter war but also to win war. Its presence, however, was not always reassuring. Three areas of the United States are studied to evaluate the social implications of the missile during these pivotal years: San Francisco, home of multiple Nike installations; of Cape Canaveral, Florida, the nation's primary missile test center; the Great Plains, the location of the largest ICBM concentration in the country. Interviews were conducted, tours of facilities were taken, and local newspapers were reviewed. In conjunction with national newspapers and magazines and public opinion polls, this information provided a local social context for missile history. Nationally and locally, Americans both feared and praised the new technology. They were anxious for government funding in their cities and often felt that the danger the missile brought to their communities by making it as a Soviet target was justified in the larger cause for national security.