A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

The Supercore for Normal Form Games

We study the supercore of a system derived from a normal form game. For the case of a finite game with pure strategies, we define a sequence of games and show that the supercore of that system coincides with the set of Nash equilibrium strategy profiles of the last game in the sequence. This result is illustrated with the characterization of the supercore for the n-person prisoners’ dilemma. With regard to the mixed extension of a normal form game, we show that the set of Nash equilibrium profiles coincides with the supercore for games with a finite number of Nash equilibria. For games with an infinite number of Nash equilibria this need not be no longer the case. Yet, it is not difficult to find a binary relation which guarantees the coincidence of these two sets.

Depletion of the heaviest stable N isotope is associated with NH4 +/NH3 toxicity in NH4 +-fed plants

Background: In plants, nitrate (NO(3)(-)) nutrition gives rise to a natural N isotopic signature (delta(15)N), which correlates with the delta(15)N of the N source. However, little is known about the relationship between the delta(15)N of the N source and the (14)N/(15)N fractionation in plants under ammonium (NH(4)(+)) nutrition. When NH(4)(+) is the major N source, the two forms, NH(4)(+) and NH(3), are present in the nutrient solution. There is a 1.025 thermodynamic isotope effect between NH(3) (g) and NH(4)(+)(aq) which drives to a different delta(15)N. Nine plant species with different NH(4)(+)-sensitivities were cultured hydroponically with NO(3)(-) or NH(4)(+) as the sole N sources, and plant growth and delta(15)N were determined. Short-term NH(4)(+)/NH(3) uptake experiments at pH 6.0 and 9.0 (which favours NH(3) form) were carried out in order to support and substantiate our hypothesis. N source fractionation throughout the whole plant was interpreted on the basis of the relative transport of NH(4)(+) and NH(3). -- Results: Several NO(3)(-)-fed plants were consistently enriched in (15)N, whereas plants under NH(4)(+) nutrition were depleted of (15)N. It was shown that more sensitive plants to NH(4)(+) toxicity were the most depleted in (15)N. In parallel, N-deficient pea and spinach plants fed with (15)NH(4)(+) showed an increased level of NH(3) uptake at alkaline pH that was related to the (15)N depletion of the plant. Tolerant to NH(4)(+) pea plants or sensitive spinach plants showed similar trend on (15)N depletion while slight differences in the time kinetics were observed during the initial stages. The use of RbNO(3) as control discarded that the differences observed arise from pH detrimental effects. -- Conclusions: This article proposes that the negative values of delta(15)N in NH(4)(+)-fed plants are originated from NH(3) uptake by plants. Moreover, this depletion of the heavier N isotope is proportional to the NH(4)(+)/NH(3) toxicity in plants species. Therefore, we hypothesise that the low affinity transport system for NH(4)(+) may have two components: one that transports N in the molecular form and is associated with fractionation and another that transports N in the ionic form and is not associated with fractionation.

"I'm on it 24/7 at the moment" : A qualitative examination of multi-screen viewing behaviours among UK 10-11 year olds

Background: Screen-viewing has been associated with increased body mass, increased risk of metabolic syndrome and lower psychological well-being among children and adolescents. There is a shortage of information about the nature of contemporary screen-viewing amongst children especially given the rapid advances in screen-viewing equipment technology and their widespread availability. Anecdotal evidence suggests that large numbers of children embrace the multi-functionality of current devices to engage in multiple forms of screen-viewing at the same time. In this paper we used qualitative methods to assess the nature and extent of multiple forms of screen-viewing in UK children. Methods: Focus groups were conducted with 10-11 year old children (n = 63) who were recruited from five primary schools in Bristol, UK. Topics included the types of screen-viewing in which the participants engaged; whether the participants ever engaged in more than one form of screen-viewing at any time and if so the nature of this multiple viewing; reasons for engaging in multi-screen-viewing; the room within the house where multi-screen-viewing took place and the reasons for selecting that room. All focus groups were transcribed verbatim, anonymised and thematically analysed. Results: Multi-screen viewing was a common behaviour. Although multi-screen viewing often involved watching TV, TV viewing was often the background behaviour with attention focussed towards a laptop, handheld device or smart-phone. There were three main reasons for engaging in multi-screen viewing: 1) tempering impatience that was associated with a programme loading; 2) multi-screen facilitated filtering out unwanted content such as advertisements; and 3) multi-screen viewing was perceived to be enjoyable. Multi-screen viewing occurred either in the child's bedroom or in the main living area of the home. There was considerable variability in the level and timing of viewing and this appeared to be a function of whether the participants attended after-school clubs. Conclusions: UK children regularly engage in two or more forms of screen-viewing at the same time. There are currently no means of assessing multi-screen viewing nor any interventions that specifically focus on reducing multi-screen viewing. To reduce children's overall screen-viewing we need to understand and then develop approaches to reduce multi-screen viewing among children.

An Overview on the Field of Micro- and Nanotechnologies for Synthetic Peptide-Based Vaccines

18 p.

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

19 p.

Two Nuclear Localization Signals in USP1 Mediate Nuclear Import of the USP1/UAF1 Complex

9 p. : il.

The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event

6 p.

Influence of nutrient intake on antioxidant capacity, muscle damage and white blood cell count in female soccer players

11 p.

Regulation of Energy Metabolism by the Extracytoplasmic Function (ECF) σ Factors of Arcobacter butzleri

11 p.

Invariant-free deduction systems for temporal logic

In this thesis we propose a new approach to deduction methods for temporal logic. Our proposal is based on an inductive definition of eventualities that is different from the usual one. On the basis of this non-customary inductive definition for eventualities, we first provide dual systems of tableaux and sequents for Propositional Linear-time Temporal Logic (PLTL). Then, we adapt the deductive approach introduced by means of these dual tableau and sequent systems to the resolution framework and we present a clausal temporal resolution method for PLTL. Finally, we make use of this new clausal temporal resolution method for establishing logical foundations for declarative temporal logic programming languages. The key element in the deduction systems for temporal logic is to deal with eventualities and hidden invariants that may prevent the fulfillment of eventualities. Different ways of addressing this issue can be found in the works on deduction systems for temporal logic. Traditional tableau systems for temporal logic generate an auxiliary graph in a first pass.Then, in a second pass, unsatisfiable nodes are pruned. In particular, the second pass must check whether the eventualities are fulfilled. The one-pass tableau calculus introduced by S. Schwendimann requires an additional handling of information in order to detect cyclic branches that contain unfulfilled eventualities. Regarding traditional sequent calculi for temporal logic, the issue of eventualities and hidden invariants is tackled by making use of a kind of inference rules (mainly, invariant-based rules or infinitary rules) that complicates their automation. A remarkable consequence of using either a two-pass approach based on auxiliary graphs or aone-pass approach that requires an additional handling of information in the tableau framework, and either invariant-based rules or infinitary rules in the sequent framework, is that temporal logic fails to carry out the classical correspondence between tableaux and sequents. In this thesis, we first provide a one-pass tableau method TTM that instead of a graph obtains a cyclic tree to decide whether a set of PLTL-formulas is satisfiable. In TTM tableaux are classical-like. For unsatisfiable sets of formulas, TTM produces tableaux whose leaves contain a formula and its negation. In the case of satisfiable sets of formulas, TTM builds tableaux where each fully expanded open branch characterizes a collection of models for the set of formulas in the root. The tableau method TTM is complete and yields a decision procedure for PLTL. This tableau method is directly associated to a one-sided sequent calculus called TTC. Since TTM is free from all the structural rules that hinder the mechanization of deduction, e.g. weakening and contraction, then the resulting sequent calculus TTC is also free from this kind of structural rules. In particular, TTC is free of any kind of cut, including invariant-based cut. From the deduction system TTC, we obtain a two-sided sequent calculus GTC that preserves all these good freeness properties and is finitary, sound and complete for PLTL. Therefore, we show that the classical correspondence between tableaux and sequent calculi can be extended to temporal logic. The most fruitful approach in the literature on resolution methods for temporal logic, which was started with the seminal paper of M. Fisher, deals with PLTL and requires to generate invariants for performing resolution on eventualities. In this thesis, we present a new approach to resolution for PLTL. The main novelty of our approach is that we do not generate invariants for performing resolution on eventualities. Our method is based on the dual methods of tableaux and sequents for PLTL mentioned above. Our resolution method involves translation into a clausal normal form that is a direct extension of classical CNF. We first show that any PLTL-formula can be transformed into this clausal normal form. Then, we present our temporal resolution method, called TRS-resolution, that extends classical propositional resolution. Finally, we prove that TRS-resolution is sound and complete. In fact, it finishes for any input formula deciding its satisfiability, hence it gives rise to a new decision procedure for PLTL. In the field of temporal logic programming, the declarative proposals that provide a completeness result do not allow eventualities, whereas the proposals that follow the imperative future approach either restrict the use of eventualities or deal with them by calculating an upper bound based on the small model property for PLTL. In the latter, when the length of a derivation reaches the upper bound, the derivation is given up and backtracking is used to try another possible derivation. In this thesis we present a declarative propositional temporal logic programming language, called TeDiLog, that is a combination of the temporal and disjunctive paradigms in Logic Programming. We establish the logical foundations of our proposal by formally defining operational and logical semantics for TeDiLog and by proving their equivalence. Since TeDiLog is, syntactically, a sublanguage of PLTL, the logical semantics of TeDiLog is supported by PLTL logical consequence. The operational semantics of TeDiLog is based on TRS-resolution. TeDiLog allows both eventualities and always-formulas to occur in clause heads and also in clause bodies. To the best of our knowledge, TeDiLog is the first declarative temporal logic programming language that achieves this high degree of expressiveness. Since the tableau method presented in this thesis is able to detect that the fulfillment of an eventuality is prevented by a hidden invariant without checking for it by means of an extra process, since our finitary sequent calculi do not include invariant-based rules and since our resolution method dispenses with invariant generation, we say that our deduction methods are invariant-free.

An Open and Social Spaced Repetition System for Language Learning

In the last decades big improvements have been done in the field of computer aided learning, based on improvements done in computer science and computer systems. Although the field has been always a bit lagged, without using the latest solutions, it has constantly gone forward taking profit of the innovations as they show up. As long as the train of the computer science does not stop (and it won’t at least in the near future) the systems that take profit of those improvements will not either, because we humans will always need to study; Sometimes for pleasure and some other many times out of need. Not all the attempts in the field of computer aided learning have been in the same direction. Most of them address one or some few of the problems that show while studying and don’t take into account solutions proposed for some other problems. The reasons for this can be varied. Sometimes the solutions simply are not compatible. Some other times, because the project is an investigation it’s interesting to isolate the problem. And, in commercial products, licenses and patents often prevent the new projects to use previous work. The world moved forward and this is an attempt to use some of the options offered by technology, mixing some old ideas with new ones.

Thrombotic Antiphospholipid Syndrome Shows Strong Haplotypic Association with SH2B3-ATXN2 Locus

Background : Thrombotic antiphospholipid syndrome is defined as a complex form of thrombophilia that is developed by a fraction of antiphospholipid antibody (aPLA) carriers. Little is known about the genetic risk factors involved in thrombosis development among aPLA carriers. Methods: To identify new loci conferring susceptibility to thrombotic antiphospholipid syndrome, a two-stage genotyping strategy was performed. In stage one, 19,000 CNV loci were genotyped in 14 thrombotic aPLA+ patients and 14 healthy controls by array-CGH. In stage two, significant CNV loci were fine-mapped in a larger cohort (85 thrombotic aPLA+, 100 non-thrombotic aPLA+ and 569 healthy controls). Results : Array-CGH and fine-mapping analysis led to the identification of 12q24.12 locus as a new susceptibility locus for thrombotic APS. Within this region, a TAC risk haplotype comprising one SNP in SH2B3 gene (rs3184504) and two SNPs in ATXN2 gene (rs10774625 and rs653178) exhibited the strongest association with thrombotic antiphospholipid syndrome (p-value = 5,9 × 10−4 OR 95% CI 1.84 (1.32–2.55)). Conclusion : The presence of a TAC risk haplotype in ATXN2-SH2B3 locus may contribute to increased thrombotic risk in aPLA carriers.

Validation of a Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR)

8 p.

Open Personalization: Involving Third Parties in Improving the User Experience of Websites

Traditional software development captures the user needs during the requirement analysis. The Web makes this endeavour even harder due to the difficulty to determine who these users are. In an attempt to tackle the heterogeneity of the user base, Web Personalization techniques are proposed to guide the users’ experience. In addition, Open Innovation allows organisations to look beyond their internal resources to develop new products or improve existing processes. This thesis sits in between by introducing Open Personalization as a means to incorporate actors other than webmasters in the personalization of web applications. The aim is to provide the technological basis that builds up a trusty environment for webmasters and companion actors to collaborate, i.e. "an architecture of participation". Such architecture very much depends on these actors’ profile. This work tackles three profiles (i.e. software partners, hobby programmers and end users), and proposes three "architectures of participation" tuned for each profile. Each architecture rests on different technologies: a .NET annotation library based on Inversion of Control for software partners, a Modding Interface in JavaScript for hobby programmers, and finally, a domain specific language for end-users. Proof-of-concept implementations are available for the three cases while a quantitative evaluation is conducted for the domain specific language.