A Restriction-Centered Theory of Reasoning and Computation to materialize a Web 3.0

Researchers suggest that personalization on the Semantic Web adds up to a Web 3.0 eventually. In this Web, personalized agents process and thus generate the biggest share of information rather than humans. In the sense of emergent semantics, which supplements traditional formal semantics of the Semantic Web, this is well conceivable. An emergent Semantic Web underlying fuzzy grassroots ontology can be accomplished through inducing knowledge from users' common parlance in mutual Web 2.0 interactions [1]. These ontologies can also be matched against existing Semantic Web ontologies, to create comprehensive top-level ontologies. On the Web, if augmented with information in the form of restrictions andassociated reliability (Z-numbers) [2], this collection of fuzzy ontologies constitutes an important basis for an implementation of Zadeh's restriction-centered theory of reasoning and computation (RRC) [3]. By considering real world's fuzziness, RRC differs from traditional approaches because it can handle restrictions described in natural language. A restriction is an answer to a question of the value of a variable such as the duration of an appointment. In addition to mathematically well-defined answers, RRC can likewise deal with unprecisiated answers as "about one hour." Inspired by mental functions, it constitutes an important basis to leverage present-day Web efforts to a natural Web 3.0. Based on natural language information, RRC may be accomplished with Z-number calculation to achieve a personalized Web reasoning and computation. Finally, through Web agents' understanding of natural language, they can react to humans more intuitively and thus generate and process information.

Change in suicide rates in Switzerland before and after firearm restriction resulting from the 2003 “Army XXI” reform

Objective: Firearms are the most common method of suicide among young men in Switzerland. From March 2003 through February 2004, the number of Swiss soldiers was halved as a result of an army reform (Army XXI), leading to a decrease in the availability of guns nationwide. The authors investigated the patterns of the overall suicide rate and the firearm suicide rate before and after the reform. Method: Using a naturalistic study design, the authors compared suicide rates before (1995–2003) and after the intervention (2004–2008) in the affected population (men ages 18–43) and in two comparison groups (women ages 18–44 and men ages 44–53). Data were received from the Swiss Federal Statistical Office. Interrupted time series analysis was used to control for preexisting temporal trends. Alternative methods (Poisson regression, autocorrelation analysis, and surrogate data tests) were used to check validity. Results: The authors found a reduction in both the overall suicide rate and the firearm suicide rate after the Army XXI reform. No significant increases were found for other suicide methods overall. An increase in railway suicides was observed. It was estimated that 22% of the reduction in firearm suicides was substituted by other suicide methods. The attenuation of the suicide rate was not compensated for during the follow-up years. Neither of the comparison groups showed statistically significant changes in firearm suicide rate and overall suicide rate. Conclusions: The restriction of firearm availability in Switzerland resulting from the Army XXI reform was followed by an enduring decrease in the general suicide rate.

Unraveling the Conformational Determinants of Peptide Dendrimers Using Molecular Dynamics Simulations

Peptide dendrimers are synthetic tree-like molecules composed of amino acids. There are at least two kinds of preferential structural behaviors exhibited by these molecules, which acquire either compact or noncompact shapes. However, the key structural determinants of such behaviors remained, until now, unstudied. Herein, we conduct a comprehensive investigation of the structural determinants of peptide dendrimers by employing long molecular dynamics simulations to characterize an extended set of third generation dendrimers. Our results clearly show that a trade-off between electrostatic effects and hydrogen bond formation controls structure acquisition in these systems. Moreover, by selectively changing the dendrimers charge we are able to manipulate the exhibited compactness. In contrast, the length of branching residues does not seem to be a major structural determinant. Our results are in accordance with the most recent experimental evidence and shed some light on the key molecular level interactions controlling structure acquisition in these systems. Thus, the results presented constitute valuable insights that can contribute to the development of truly tailor-made dendritic systems.

Bilateral uterine vessel ligation as a model of intrauterine growth restriction in mice

BACKGROUND Intrauterine growth restriction (IUGR) occurs in up to 10% of pregnancies and is considered as a major risk to develop various diseases in adulthood, such as cardiovascular diseases, insulin resistance, hypertension or end stage kidney disease. Several IUGR models have been developed in order to understand the biological processes linked to fetal growth retardation, most of them being rat or mouse models and nutritional models. In order to reproduce altered placental flow, surgical models have also been developed, and among them bilateral uterine ligation has been frequently used. Nevertheless, this model has never been developed in the mouse, although murine tools display multiple advantages for biological research. The aim of this work was therefore to develop a mouse model of bilateral uterine ligation as a surgical model of IUGR. RESULTS In this report, we describe the set up and experimental data obtained from three different protocols (P1, P2, P3) of bilateral uterine vessel ligation in the mouse. Ligation was either performed at the cervical end of each uterine horn (P1) or at the central part of each uterine horn (P2 and P3). Time of surgery was E16 (P1), E17 (P2) or E16.5 (P3). Mortality, maternal weight and abortion parameters were recorded, as well as placentas weights, fetal resorption, viability, fetal weight and size. Results showed that P1 in test animals led to IUGR but was also accompanied with high mortality rate of mothers (50%), low viability of fetuses (8%) and high resorption rate (25%). P2 and P3 improved most of these parameters (decreased mortality and improved pregnancy outcomes; improved fetal viability to 90% and 27%, respectively) nevertheless P2 was not associated to IUGR contrary to P3. Thus P3 experimental conditions enable IUGR with better pregnancy and fetuses outcomes parameters that allow its use in experimental studies. CONCLUSIONS Our results show that bilateral uterine artery ligation according to the protocol we have developed and validated can be used as a surgical mouse model of IUGR.

Conformational diversity versus nucleic acid triplex stability, a combinatorial study

The stability of a triple helix formed between a DNA duplex and an incoming oligonucleotide strand strongly depends on the solvent conditions and on intrinsic chemical and conformational factors. Attempts to increase triple helix stability in the past included chemical modification of the backbone, sugar ring, and bases in the third strand. However, the predictive power of such modifications is still rather poor. We therefore developed a method that allows for rapid screening of conformationally diverse third strand oligonucleotides for triplex stability in the parallel pairing motif to a given DNA double helix sequence. Combinatorial libraries of oligonucleotides of the requisite (fixed) base composition and length that vary in their sugar unit (ribose or deoxyribose) at each position were generated. After affinity chromatography against their corresponding immobilized DNA target duplex, utilizing a temperature gradient as the selection criterion, the oligonucleotides forming the most stable triple helices were selected and characterized by physicochemical methods. Thus, a series of oligonucleotides were identified that allowed us to define basic rules for triple helix stability in this conformationally diverse system. It was found that ribocytidines in the third strand increase triplex stability relative to deoxyribocytidines independently of the neighboring bases and position along the strand. However, remarkable sequence-dependent differences in stability were found for (deoxy)thymidines and uridines

Nucleic-Acid Analogs with Restricted Conformational Flexibility in the Sugar-Phosphate Backbone (‘Bicyclo-DNA’). Part 5. Synthesis, Characterization, and Pairing Properties of Oligo-αlpha-D-(bicyclodeoxynucleotides) of the Bases Adenine and Thymine (αlpha-Bicyclo-DNA)

10.1002/hlca.19950780816.abs A conformational analysis of the (3′S,5′R)-2′-deoxy-3′,5′-ethano-α-D-ribonucleosides (a-D-bicyclodeoxynucleosides) based on the X-ray analysis of N4-benzoyl-α-D-(bicyclodeoxycytidine) 6 and on 1H-NMR analysis of the α-D-bicyclodeoxynucleoside derivatives 1-7 reveals a rigid sugar structure with the furanose units in the l′-exo/2′-endo conformation and the secondary OH groups on the carbocyclic ring in the pseudoequatorial orientation. Oligonucleotides consisting of α-D-bicyclothymidine and α-D-bicyclodeoxyadenosine were successfully synthesized from the corresponding nucleosides by phosphoramidite methodology on a DNA synthesizer. An evaluation of their pairing properties with complementary natural RNA and DNA by means of UV/melting curves and CD spectroscopy show the following characteristics: i) α-bcd(A10) and α-bcd(T10) (α = short form of α-D)efficiently form complexes with complementary natural DNA and RNA. The stability of these hybrids is comparable or slightly lower as those with natural β-d(A10) or β-d(T10)( β = short form ofβ-D). ii) The strand orientation in α-bicyclo-DNA/β-DNA duplexes is parallel as was deduced from UV/melting curves of decamers with nonsymmetric base sequences. iii) CD Spectroscopy shows significant structural differences between α-bicyclo-DNA/β-DNA duplexes compared to α-DNA/β-DNA duplexes. Furthermore, α-bicyclo-DNA is ca. 100-fold more resistant to the enzyme snake-venom phosphodiesterase with respect to β-DNA and about equally resistant as α-DNA.