Memorandum of material furnished for superstructure on the line of the Port Dalhousie Thorold Railway by contract

Memorandum of material furnished for superstructure on the line of the Port Dalhousie Thorold Railway by contract. This document includes: Bills of timber, memorandums of planking, fencing, ties, track laying, masonry and bolts and spikes. There are also diagrams of culverts. One of the pages is loose and the outer pages are somewhat discoloured (32 pages, handwritten and bound with ribbon, n.d.

Describing Web Service Architectures through Design-by-Contract

Architectural description languages (ADLs) are used to specify a high-level, compositional view of a software application, specifying how a system is to be composed from coarse-grain components. ADLs usually come equipped with a formal dynamic semantics, facilitating specification and analysis of distributed and event-based systems. In this paper, we describe the TrustME, an ADL framework that provides both a process and a structural view of web service-based systems. We use Petri-net descriptions to give a dynamic view of business workflow for web service collaboration. We adapt the approach of Schmidt to define a form of Meyer's design-by-contract for configuring workflow architectures. This serves as a configuration-level means of constructing safer, more robust systems.

Trust-By-Contract: Modelling, Analysing and Predicting Behaviour in Software Architectures

Architecture description languages (ADLs) are used to specify high-level, compositional views of a software application. ADL research focuses on software composed of prefabricated parts, so-called software components. ADLs usually come equipped with rigorous state-transition style semantics, facilitating verification and analysis of specifications. Consequently, ADLs are well suited to configuring distributed and event-based systems. However, additional expressive power is required for the description of enterprise software architectures – in particular, those built upon newer middleware, such as implementations of Java’s EJB specification, or Microsoft’s COM+/.NET. The enterprise requires distributed software solutions that are scalable, business-oriented and mission-critical. We can make progress toward attaining these qualities at various stages of the software development process. In particular, progress at the architectural level can be leveraged through use of an ADL that incorporates trust and dependability analysis. Also, current industry approaches to enterprise development do not address several important architectural design issues. The TrustME ADL is designed to meet these requirements, through combining approaches to software architecture specification with rigorous design-by-contract ideas. In this paper, we focus on several aspects of TrustME that facilitate specification and analysis of middleware-based architectures for trusted enterprise computing systems.

Financial Planning by Contract Food Service Management Companies

Drugs in the workplace is a growing problem that threatens a valuable human resource - the employee. Managers in the hospitality industry can take a proactive stance in meeting the problem head on. The authors discuss what managers can do.

Peut-on donner d’une clause et reprendre de l’autre? Essai sur la cause comme instrument de contrôle de la cohérence matérielle du contrat

Peut-on donner d’une clause et reprendre de l’autre? Si deux siècles de décisions et de commentaires contradictoires empêchent de répondre à cette question avec la certitude et l’assurance auxquelles nous a habitué la doctrine civiliste, il est tout de même possible d’affirmer que le droit civil prohibe la clause qui permet à un contractant de se dédire totalement de son engagement. Privant l’engagement de son cocontractant de toute raison, et le contrat dans lequel elle se trouve de toute fonction, cette clause contracticide se heurte en effet à une notion fondamentale du droit commun des contrats : la cause. C’est pour éviter que ne soient validés les contrats qui ne présentent aucun intérêt pour l’une ou l’autre des parties que le législateur québécois a choisi d’importer – et de conserver, dans son article introductif du Livre des obligations, cette notion que l’on dit la plus symbolique du droit français des obligations. En effet, bien que son rôle soit fréquemment assumé par d’autres mécanismes, la cause demeure la gardienne des fonctions du contrat synallagmatique. À ce titre, elle permet non seulement d’annuler les contrats qui ne codifient aucun échange, mais également, et surtout, de contrôler ceux dont le contenu ne permet pas de matérialiser les avantages négociés. Octroyant au juge le pouvoir d’assurer que le contrat contienne les outils nécessaires et adaptés à la réalisation de l’opération qu’il a pour fonction de mettre en œuvre, la cause lui offre donc le moyen de garantir l’adéquation entre la fin et ses moyens, bref de contrôler la cohérence matérielle du contrat.

Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 µg DNA-HSP65. on day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.

Contractual restrictions on lawful use of information: sole-source databases protected by the back door?

This article is concerned with the risks associated with the monopolisation of information that is available from a single source only. Although there is a longstanding consensus that sole-source databases should not receive protection under the EU Database Directive, and there are legislative provisions to ensure that lawful users have access to a database’s contents, Ryanair v PR Aviation challenges this assumption by affirming that the use of non-protected databases can be restricted by contract. Owners of non-protected databases can contractually exclude lawful users from taking the benefit of statutorily permitted uses, because such databases are not covered from the legislation that declares this kind of contract null and void. We argue that this judgment is not consistent with the legislative history and can have a profound impact on the functioning of the digital single market, where new information services, such as meta-search engines or price-comparison websites, base their operation on the systematic extraction and re-utilisation of materials available from online sources. This is an issue that the Commission should address in a forthcoming evaluation of the Database Directive.

Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Preventing parasite load and maternofoetal transmission

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Tissue parasitic load and lactogenic quantification

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Maternal LAMP/p55gagHIV-1 DNA Immunization Induces In Utero Priming and a Long-Lasting Immune Response in Vaccinated Neonates

Infants born to HIV-infected mothers are at high risk of becoming infected during gestation or the breastfeeding period. A search is thus warranted for vaccine formulations that will prevent mother-to-child HIV transmission. The LAMP/gag DNA chimeric vaccine encodes the HIV-1 p55gag fused to the lysosome-associated membrane protein-1 (LAMP-1) and has been shown to enhance anti-Gag antibody (Ab) and cellular immune responses in adult and neonatal mice; such a vaccine represents a new concept in antigen presentation. In this study, we evaluated the effect of LAMP/gag DNA immunization on neonates either before conception or during pregnancy. LAMP/gag immunization of BALB/c mice before conception by the intradermal route led to the transfer of anti-Gag IgG1 Ab through the placenta and via breastfeeding. Furthermore, there were an increased percentage of CD4+ CD25+ Foxp3+ T cells in the spleens of neonates. When offspring were immunized with LAMP/gag DNA, the anti-Gag Ab response and the Gag-specific IFN-gamma-secreting cells were decreased. Inhibition of anti-Gag Ab production and cellular responses were not observed six months after immunization, indicating that maternal immunization did not interfere with the long-lasting memory response in offspring. Injection of purified IgG in conjunction with LAMP/gag DNA immunization decreased humoral and cytotoxic T-cell responses. LAMP/gag DNA immunization by intradermal injection prior to conception promoted the transfer of Ab, leading to a diminished response to Gag without interfering with the development of anti-Gag T- and B-cell memory. Finally, we assessed responses after one intravenous injection of LAMP/gag DNA during the last five days of pregnancy. The intravenous injection led to in utero immunization. In conclusion, DNA vaccine enconding LAMP-1 with Gag and other HIV-1 antigens should be considered in the development of a protective vaccine for the maternal/fetal and newborn periods.

The Influence of Immunization Route on the Adjuvant Effect of alpha-Galactosylceramide

Potent vaccine formulations ideally include adjuvants to activate innate immune responses and enhance antigen-specific adaptive immunity. The synthetic glycolipid alpha-Galactosylceramide (α-GalCer) effectively activates the innate immune mediating NKT cells to produce cytokines and activate downstream immune cells, resulting in development of humoral and cell mediated immune responses to co-administered antigens. While a single intravenous immunization of α-GalCer strongly activates NKT cells, multiple doses by this route are well documented to induce anergy in NKT cells. Anergy is defined as the deficiency in NKT proliferation and cytokine production, including IL-4 and IFNγ. However, our studies have shown that two doses of α-GalCer administered intranasally by the intranasal route leads to reactivation of NKT cells and improved adaptive immune responses after each subsequent dose. I therefore investigated the role of multiple routes of immunization in activation of NKT cells, i.e. anergy versus repeated activation. Specifically, I hypothesized that the differential capacity of NKT cells to produce IFNγ, as a result of route of immunization with α-GalCer, influences the induction of adaptive immune responses to co-administered antigen. Our experimental design utilizes the observation that intranasal immunization primarily induces immune responses in the lungs while intravenous immunization induces responses in the liver. Using intracellular cytokine staining for IFNγ production and Elispot analyses for determining NKT and T cell activation, respectively, it was determined that administering two consecutive intravenous doses resulted in anergy to NKT cells (no IFNγ production) in the liver and lack of adaptive immunity while second immunization by the intranasal route overcame anergy in the lung. The outcome in the other tissues analyzed was mixed and could be the result of tissue microenvironment among others possible reasons. When intranasal dosing preceded systemic, NKT cells were reactivated to produce IFNγ and induced positive adaptive immune responses in the responding lung tissue. These results indicate that the mechanism by which mucosal and systemic immunization routes activate NKT cells may differ in that there is a differential tissue-specific effect induced by each route. Future studies are necessary to determine the reason for these tissue-specific effects and how they relate to NKT cell activation.

DNA immunization: Induction of higher avidity antibody and effect of route on T cell cytotoxicity

Immunizations of mice with plasmid DNAs encoding ovalbumin (OVA), human Ig, and hen egg lysozyme were compared with doses of soluble protein (without adjuvant) that induced similar IgG responses. The route of immunization influenced the magnitude of the antibody (Ab) response in that intradermal (i.d.) injection elicited higher IgG Ab levels than i.m. injection in both DNA- and protein-immunized mice. Although total IgG levels were similar to soluble protein controls, the avidity of the anti-OVA Abs generated by DNA immunization were 100- and 1,000-fold higher via the i.m. or i.d. route, respectively. However, despite the generation of high-avidity Ab in DNA-immunized mice, germinal centers could not be detected in either DNA- or protein-immunized mice. Examination of the IgG subclass response showed that IgG2a was induced by i.m. DNA immunization, coinciding with elevated interferon γ production, whereas a dominant and elevated IgG1 response, coinciding with detectable interleukin 4 production, was generated after i.d. immunization with DNA or soluble OVA and hen egg lysozyme but not human Ig protein. As expected, cytotoxic T cell (CTL) responses could be detected only after DNA immunization. I.d. immunization produced the strongest CTL responses early (2 weeks) but was similar to i.m. later. Therefore, DNA immunization can differ from protein immunization by its ability to induce rapid CTL responses and higher avidity Ab, both of which are advantageous for vaccination.

Ecological restoration across the Mediterranean Basin as viewed by practitioners

Restoration efforts in the Mediterranean Basin have been changing from a silvicultural to an ecological restoration approach. Yet, to what extent the projects are guided by ecological restoration principles remains largely unknown. To analyse this issue, we built an on-line survey addressed to restoration practitioners. We analysed 36 restoration projects, mostly from drylands (86%). The projects used mainly soil from local sources. The need to comply with legislation was more important as a restoration motive for European Union (EU) than for non-EU countries, while public opinion and health had a greater importance in the latter. Non-EU countries relied more on non-native plant species than EU countries, thus deviating from ecological restoration guidelines. Nursery-grown plants used were mostly of local or regional provenance, whilst seeds were mostly of national provenance. Unexpected restoration results (e.g. inadequate biodiversity) were reported for 50% of the projects and restoration success was never evaluated in 22%. Long term evaluation (> 6 years) was only performed in 31% of cases, and based primarily on plant diversity and cover. The use of non-native species and species of exogenous provenances may: i) entail the loss of local genetic and functional trait diversity, critical to cope with drought, particularly under the predicted climate change scenarios, and ii) lead to unexpected competition with native species and/or negatively impact local biotic interactions. Absent or inappropriate monitoring may prevent the understanding of restoration trajectories, precluding adaptive management strategies, often crucial to create functional ecosystems able to provide ecosystem services. The overview of ecological restoration projects in the Mediterranean Basin revealed high variability among practices and highlighted the need for improved scientific assistance and information exchange, greater use of native species of local provenance, and more long-term monitoring and evaluation, including functional and ecosystem services' indicators, to improve and spread the practice of ecological restoration.

Active and passive immunization against oral Candida albicans infection in a murine model

Background/aims: Clinical and laboratory studies are consistent with a major role for cell-mediated immunity in recovery from oral infection with Candida albicans, but the role of humoral immunity remains controversial. The purpose of this study was to establish the relative contributions of cellular and humoral immunity to protection against oral candidiasis in a murine model, and to determine whether host responses could be enhanced by different immunization strategies. Results: Active oral immunization was protective in BALB/c and CBA/CaH mice, reducing both fungal burden and duration of infection after secondary challenge, whereas systemic immunization failed to protect against subsequent oral challenge. Candida-specific IgM was the predominant antibody detected in serum following both primary and secondary oral challenge; however, Candida-specific salivary IgA was not detectable. Immunization by passive transfer of either lymphocytes or immune serum did not confer any significant protection against oral infection in either susceptible or resistant mouse strain. Conclusion: The data demonstrate a possible role for mucosa-associated immunity following active immunization by the oral route, most likely exerted by local T lymphocytes resident in the oral mucosa, but there was no evidence to support a role for humoral immunity in protection against oral candidiasis.