272 research outputs found

    Linearly bounded infinite graphs

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    Linearly bounded Turing machines have been mainly studied as acceptors for context-sensitive languages. We define a natural class of infinite automata representing their observable computational behavior, called linearly bounded graphs. These automata naturally accept the same languages as the linearly bounded machines defining them. We present some of their structural properties as well as alternative characterizations in terms of rewriting systems and context-sensitive transductions. Finally, we compare these graphs to rational graphs, which are another class of automata accepting the context-sensitive languages, and prove that in the bounded-degree case, rational graphs are a strict sub-class of linearly bounded graphs

    On a Conjecture of Rapoport and Zink

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    In their book Rapoport and Zink constructed rigid analytic period spaces FwaF^{wa} for Fontaine's filtered isocrystals, and period morphisms from PEL moduli spaces of pp-divisible groups to some of these period spaces. They conjectured the existence of an \'etale bijective morphism FaFwaF^a \to F^{wa} of rigid analytic spaces and of a universal local system of QpQ_p-vector spaces on FaF^a. For Hodge-Tate weights n1n-1 and nn we construct in this article an intrinsic Berkovich open subspace F0F^0 of FwaF^{wa} and the universal local system on F0F^0. We conjecture that the rigid-analytic space associated with F0F^0 is the maximal possible FaF^a, and that F0F^0 is connected. We give evidence for these conjectures and we show that for those period spaces possessing PEL period morphisms, F0F^0 equals the image of the period morphism. Then our local system is the rational Tate module of the universal pp-divisible group and enjoys additional functoriality properties. We show that only in exceptional cases F0F^0 equals all of FwaF^{wa} and when the Shimura group is GLnGL_n we determine all these cases.Comment: v2: 48 pages; many new results added, v3: final version that will appear in Inventiones Mathematica

    The dynamics of university units as a multi-level process. Credibility cycles and resource dependencies

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    This paper presents an analysis of resource acquisition and profile development of institutional units within universities. We conceptualize resource acquisition as a two level nested process, where units compete for external resources based on their credibility, but at the same time are granted faculty positions from the larger units (department) to which they belong. Our model implies that the growth of university units is constrained by the decisions of their parent department on the allocation of professorial positions, which represent the critical resource for most units’ activities. In our field of study this allocation is largely based on educational activities, and therefore, units with high scientific credibility are not necessarily able to grow, despite an increasing reliance on external funds. Our paper therefore sheds light on the implications that the dual funding system of European universities has for the development of units, while taking into account the interaction between institutional funding and third-party funding

    Exacerbation of cigarette smoke-induced pulmonary inflammation by Staphylococcus aureus Enterotoxin B in mice

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    <p>Abstract</p> <p>Background</p> <p>Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with <it>Staphylococcus aureus </it>results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.</p> <p>Objective</p> <p>To study the effect of <it>Staphylococcus aureus </it>enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.</p> <p>Methods</p> <p>C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.</p> <p>Results</p> <p>Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8<sup>+ </sup>T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.</p> <p>Conclusions</p> <p>Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that <it>Staphylococcus aureus </it>could influence the pathogenesis of COPD.</p

    Penetrance of HNPCC-related cancers in a retrolective cohort of 12 large Newfoundland families carrying a MSH2 founder mutation: an evaluation using modified segregation models

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    <p>Abstract</p> <p>Background</p> <p>Accurate risk (penetrance) estimates for associated phenotypes in carriers of a major disease gene are important for genetic counselling of at-risk individuals. Population-specific estimates of penetrance are often needed as well. Families ascertained from high-risk disease clinics provide substantial data to estimate penetrance of a disease gene, but these estimates must be adjusted for possible specific sources of bias.</p> <p>Methods</p> <p>A cohort of 12 independently ascertained HNPCC families harbouring a founder MSH2 mutation was identified from a cancer genetics clinic in St. John's, Newfoundland, Canada. Carrier status was known for 247 family members but phenotype information on up to 85 additional relatives with unknown carrier status was available; using modified segregation models these additional individuals could be included in the analyses. Three HNPCC-related phenotypes were evaluated as age at diagnosis of: any HNPCC cancer (first cancer), colorectal cancer (CRC), and endometrial cancer (EC) for females.</p> <p>Results</p> <p>Lifetime (age 70) risk estimates for male and female carriers were similar for developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%, 99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced substantially reduced lifetime risk for developing CRC compared to male carriers (Females = 38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non-carriers had very low lifetime risk for these two outcomes while male non-carriers had lifetime risks intermediate to the female carriers and non-carriers. Female carriers had a lifetime risk of developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to non-carriers) were substantially greater for females compared to their male counterparts (Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for developing CRC at age 70 were substantially greater for females compared to their male counterparts (Females = 23.7, 95%CI = (5.6, 137.9); Males = 6.8%, 95% CI = (2.3, 66.2)). However, the risk of developing CRC decreased with age among both genders.</p> <p>Conclusion</p> <p>The proposed modified segregation-based models used to estimate age-specific risks for HNPCC phenotypes can reduce bias due to ascertainment and missing genotype information as well as provide estimates of absolute and relative risks.</p

    Whole-genome sequencing analysis of semi-supercentenarians

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    Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events

    Using Affiliation Networks to Study the Determinants of Multilateral Research Cooperation Some empirical evidence from EU Framework Programs in biotechnology

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    This paper studies multilateral cooperation networks among organizations and work on a two-mode representation to study the decision to participate in a consortium. Our objective is to explain the underlying processes that give rise to multilateral collaboration networks. Particularly, we are interested in how heterogeneity in organizations' attributes plays a part and in the geographical dimension of this formation process. We use the data on project proposals submitted to the 7th Framework Program (FP) in the area of Life sciences, Biotechnology and Biochemistry for Sustainable Non-Food. We employ exponential random graph models (p* models) (Frank and Strauss, 1986 ; Wasserman and Pattison, 1996) with node attributes (Agneessens et al., 2004), and we make use of extensions for affiliation networks (Wang et al., 2009). These models do not only enable handling variability in consortium sizes but also relax the assumption on tie/triad independence. We obtained some preliminary results indicating institutional types as a source of heterogeneity affecting participation decisions. Also, these initial results point out that organizations take their potential partners' participations in other projects into account in giving their decision ; organizations located in the core European countries tend to participate in the same project ; the tendency to preserve the composition of a consortium across projects and the tendency of organizations with the same institutional type to co-participate are not significant

    Fishing for complementarities : competitive research funding and research productivity

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    This paper empirically investigates complementarities between different sources of research funding with regard to academic publishing. We find for a sample of UK engineering academics that competitive funding is associated with an increase in ex-post publications but that industry funding decreases the marginal utility of public funding by lowering the publication and citation rate increases associated with public grants. However, when holding all other explanatory variables at their mean, the negative effect of the interaction does not translate into an effective decrease in publication and citation numbers. The paper also shows that the positive effect of public funding is driven by UK research council and charity grants and that EU funding has no significant effect on publication outcomes

    Academic patenting: the importance of industry support

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    This paper provides evidence that university-industry collaboration is important for turning commercial opportunities into patents. The results suggest that researchers who receive a large share of research grants from industry have a higher propensity to file a patent. Small dissemination grants generally exert a positive effect, whether they come from industry or not. It also finds that these interactions do not increase the number of industry owned patents alone but benefit universities’ commercialisation efforts in general
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