Interleukin-12 and protective immunity to schistosomes

The attenuated vaccine against Schistosoma mansoni induces Th1-mediated protective immunity and we have sought to identify a role for IL-12 in this model. Elevated levels of IL-12 (p40 mRNA) were detected in the lymph nodes (LN) and the lungs of vaccinated mice, whilst treatment of vaccinated mice with anti-IL-12 antibodies decreased the ratio of IFNg:IL-4 secreted by in vitro-cultured LN cells. However, there was only marginal abrogation of the level of resistance in these mice. Soluble antigens from the lung-stage of the parasite (SLAP) appeared to be efficient stimulators of IFNg and IL-12 secretion. These antigens when used to immunise mice in conjunction with IL-12 as an adjuvant, elicited a polarised Th1 response with abundant IFNg secretion but no IL-4. This immunisation regime also induced significant protection against reinfection, whereas inoculation of mice with SLAP alone did not. The induction of a dominant Th1 response using SLAP + IL-12 probably operates via IFNg production by natural killer (NK) cells stimulated by IL-12, since in vivo ablation of NK cells using anti-NK1.1 antibody reduced CD4+-dependent IFNg production from cultured LN cells by over 97%. Nevertheless, in mice with a genetic disruption of the IFNg receptor, administration of SLAP + IL-12 induced levels of IFNg equal to those in wild-type mice, thus showing that in this model IL-12 can directly prime T cells independent of IFNg. Clearly, IL-12 has a critical role in protective immunity to schistosomes and it may aid the development of an effective vaccine against this disease

Feasibility study of submerged membrane bioreactor (MBR) as an alternative to conventional activated sludge process (CASP) for municipal wastewater treatment: A pilot scale study

The conventional activated sludge processes (CAS) for the treatment of municipal wastewater are going to be outdated gradually due to more stringent environmental protection laws and regulations. The Membrane bioreactors (MBRs) are the most promising modern technology widely accepted in the world of wastewater treatment due to their highly pronounced features such as high quality effluent, less foot print and working under high MLSS concentration. This research project was carried out to investigate the feasibility and effectiveness of MBR technology compare to the CAS process based on the scientific facts and results. The pilot scale MBR pilot plant was run for more than 150 days and the analysis results were evaluated. The prime focus of the project was to evaluate the correlation of permeate flux under different operating MLSS concentrations. The permeate flux was found almost constant regardless of variations in MLSS concentrations. The removal of micropollutant such as heavy metals, PCPPs, PFCs, steroidal hormones was also studied. The micropollutant removal performance of MBR process was found relatively effective than CAS process. Furthermore, the compatibility of submerged membranes within the bioreactor had truly reduced the process footprint.

Priming effects of a peripheral visual stimulus in simple and go/no-go tasks

The early facilitatory effect of a peripheral spatially visual prime stimulus described in the literature for simple reaction time tasks has been usually smaller than that described for complex (go/no-go, choice) reaction time tasks. In the present study we investigated the reason for this difference. In a first and a second experiment we tested the participants in both a simple task and a go/no-go task, half of them beginning with one of these tasks and half with the other one. We observed that the prime stimulus had an early effect, inhibitory for the simple task and facilitatory for the go/no-go task, when the task was performed first. No early effect appeared when the task was performed second. In a third and a fourth experiment the participants were, respectively, tested in the simple task and in the go/no-go task for four sessions (the prime stimulus was presented in the second, third and fourth sessions). The early effects of the prime stimulus did not change across the sessions, suggesting that a habituatory process was not the cause for the disappearance of these effects in the first two experiments. Our findings are compatible with the idea that different attentional strategies are adopted in simple and complex reaction time tasks. In the former tasks the gain of automatic attention mechanisms may be adjusted to a low level and in the latter tasks, to a high level. The attentional influence of the prime stimulus may be antagonized by another influence, possibly a masking one.

Contemporary marketing in the high-tech industry: Perceptions of Finnish IT marketing professionals

Over the last 30 years, new technologies and globalization have radically changed the way in which marketing is conducted. However, whereas their effects on business in general have been widely discussed, the focus of the effects on marketing remains without clear recognition. Global research has been made to shed light onto the issue, but it has widely concentrated on the views of executives as well as the consumer markets. In addition, a research gap is existent in applying the concept of marketing change in a specific business-to-business (B2B) industry. Therefore, the main research question this study seeks to answer is: “How is contemporary marketing conducted in the high-technology industry?” In this research, the researcher considers the specific industry of high-technology. However, as the industry is comprised of differing markets, the focus will be given to one of the industry’s prime sectors – the information technology (IT) markets, where companies offer other firms products or services manufactured with advanced technology. The growing IT-market is considered of critical importance in the economies of technologically ready countries such as Finland, where this research is also conducted. Through multiple case studies the researcher aims to describe how the changes in technology, customer engagement and future trends have shaped the way in which successful high-tech marketing is conducted in today’s marketplace. Then, results derived from the empirical research are presented to the reader with links to existing literature. As a conclusion, a generalized framework is constructed to depict and ideal marketer-customer relationship, with emphasis on dynamic, two-way communication and its supporting elements of customer analytics, change adaptation, strategic customer communication and organizational support. From a managerial point of view, the research may provide beneficial information as contemporary marketing can yield profitable outcomes if managed correctly. As a new way to grasp competitive advantage, strategic marketing is much more data-driven and customer-focused than ever before. The study can also prove to be relevant for the academic communities, while its results may act as inspiring for new focus on the education trends of future marketers. This study was limited to the internal activities done at the high-tech industry, leaving out the considerations for co-marketing, marketing via business partners or marketing at other B2B-industries.

Evidence for divided automatic attention

A long-standing debate in the literature is whether attention can form two or more independent spatial foci in addition to the well-known unique spatial focus. There is evidence that voluntary visual attention divides in space. The possibility that this also occurs for automatic visual attention was investigated here. Thirty-six female volunteers were tested. In each trial, a prime stimulus was presented in the left or right visual hemifield. This stimulus was characterized by the blinking of a superior, middle or inferior ring, the blinking of all these rings, or the blinking of the superior and inferior rings. A target stimulus to which the volunteer should respond with the same side hand or a target stimulus to which she should not respond was presented 100 ms later in a primed location, a location between two primed locations or a location in the contralateral hemifield. Reaction time to the positive target stimulus in a primed location was consistently shorter than reaction time in the horizontally corresponding contralateral location. This attentional effect was significantly smaller or absent when the positive target stimulus appeared in the middle location after the double prime stimulus. These results suggest that automatic visual attention can focus on two separate locations simultaneously, to some extent sparing the region in between.

Immune strategies using single-component LipL32 and multi-component recombinant LipL32-41-OmpL1 vaccines against leptospira

Genes encoding lipoproteins LipL32, LipL41 and the outer-membrane protein OmpL1 of leptospira were recombined and cloned into a pVAX1 plasmid. BALB/c mice were immunized with LipL32 and recombined LipL32-41-OmpL1 using DNA-DNA, DNA-protein and protein-protein strategies, respectively. Prime immunization was on day 1, boost immunizations were on day 11 and day 21. Sera were collected from each mouse on day 35 for antibody, cytokine detection and microscopic agglutination test while spleen cells were collected for splenocyte proliferation assay. All experimental groups (N = 10 mice per group) showed statistically significant increases in antigen-specific antibodies, in cytokines IL-4 and IL-10, as well as in the microscopic agglutination test and splenocyte proliferation compared with the pVAX1 control group. The groups receiving the recombined LipL32-41-OmpL1 vaccine induced anti-LipL41 and anti-OmpL1 antibodies and yielded better splenocyte proliferation values than the groups receiving LipL32. DNA prime and protein boost immune strategies stimulated more antibodies than a DNA-DNA immune strategy and yielded greater cytokine and splenocyte proliferation than a protein-protein immune strategy. It is clear from these results that recombination of protective antigen genes lipL32, lipL41, and ompL1 and a DNA-protein immune strategy resulted in better immune responses against leptospira than single-component, LipL32, or single DNA or protein immunization.

Leukotrienes are not essential for the efficacy of a heterologous vaccine against Mycobacterium tuberculosis infection

Leukotrienes are reported to be potent proinflammatory mediators that play a role in the development of several inflammatory diseases such as asthma, rheumatoid arthritis and periodontal disease. Leukotrienes have also been associated with protection against infectious diseases. However, the role of leukotrienes in Mycobacterium tuberculosis infection is not understood. To answer this question, we studied the role of leukotrienes in the protective immune response conferred by prime-boost heterologous immunization against tuberculosis. We immunized BALB/c mice (4-11/group) with subcutaneous BCG vaccine (1 x 10(5) M. bovis BCG) (prime) followed by intramuscular DNA-HSP65 vaccine (100 µg) (boost). During the 30 days following the challenge, the animals were treated by gavage daily with MK-886 (5 mg·kg-1·day-1) to inhibit leukotriene synthesis. We showed that MK-886-treated mice were more susceptible to M. tuberculosis infection by counting the number of M. tuberculosis colony-forming units in lungs. The histopathological analysis showed an impaired influx of leukocytes to the lungs of MK-886-treated mice after infection, confirming the involvement of leukotrienes in the protective immune response against experimental tuberculosis. However, prime-boost-immunized mice treated with MK-886 remained protected after challenge with M. tuberculosis, suggesting that leukotrienes are not required for the protective effect elicited by immunization. Protection against M. tuberculosis challenge achieved by prime-boost immunization in the absence of leukotrienes was accompanied by an increase in IL-17 production in the lungs of these animals, as measured by ELISA. Therefore, these data suggest that the production of IL-17 in MK-886-treated, immunized mice could contribute to the generation of a protective immune response after infection with M. tuberculosis.

Identification of fungemia agents using the polymerase chain reaction and restriction fragment length polymorphism analysis

Prompt and specific identification of fungemia agents is important in order to define clinical treatment. However, in most cases conventional culture identification can be considered to be time-consuming and not without errors. The aim of the present study was to identify the following fungemia agents: Candida albicans, Candida parapsilosis, Candida tropicalis, Candida glabrata, Cryptococcus neoformans, Cryptococcus gattii, and Histoplasma capsulatum using the polymerase chain reaction and restriction fragment length polymorphism analysis (PCR/RFLP). More specifically: a) to evaluate 3 different amplification regions, b) to investigate 3 different restriction enzymes, and c) to use the best PCR/RFLP procedure to indentify 60 fungemia agents from a culture collection. All 3 pairs of primers (ITS1/ITS4, NL4/ITS5 and Primer1/Primer2) were able to amplify DNA from the reference strains. However, the size of these PCR products did not permit the identification of all the species studied. Three restriction enzymes were used to digest the PCR products: HaeIII, Ddel and Bfal. Among the combinations of pairs of primers and restriction enzymes, only one (primer pair NL4/ITS5 and restriction enzyme Ddel) produced a specific RFLP pattern for each microorganism studied. Sixty cultures of fungemia agents (selected from the culture collection of Fundação de Medicina Tropical do Amazonas - FMTAM) were correctly identified by PCR/RFLP using the prime pair NL4/ITS5 and Ddel. We conclude that the method proved to be both simple and reproducible, and may offer potential advantages over phenotyping methods.

Recombinant vaccines and the development of new vaccine strategies

Vaccines were initially developed on an empirical basis, relying mostly on attenuation or inactivation of pathogens. Advances in immunology, molecular biology, biochemistry, genomics, and proteomics have added new perspectives to the vaccinology field. The use of recombinant proteins allows the targeting of immune responses focused against few protective antigens. There are a variety of expression systems with different advantages, allowing the production of large quantities of proteins depending on the required characteristics. Live recombinant bacteria or viral vectors effectively stimulate the immune system as in natural infections and have intrinsic adjuvant properties. DNA vaccines, which consist of non-replicating plasmids, can induce strong long-term cellular immune responses. Prime-boost strategies combine different antigen delivery systems to broaden the immune response. In general, all of these strategies have shown advantages and disadvantages, and their use will depend on the knowledge of the mechanisms of infection of the target pathogen and of the immune response required for protection. In this review, we discuss some of the major breakthroughs that have been achieved using recombinant vaccine technologies, as well as new approaches and strategies for vaccine development, including potential shortcomings and risks.

Alzheimer's disease: is a vaccine possible?

The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of β-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting β-amyloid in the brain. Adverse effects observed in a clinical trial based on the β-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the β-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.

Política industrial e desenvolvimento

This paper aims at contributing to the debate on industrial policy and economic development in Brazil. At first, theoretical approaches that support industrial policy-making are discussed, with emphasis on the neoschumpeterian/evolutionary approach, which focuses on innovation as prime mover of economic development and on the co-evolution of technologies, institutions, and industries and firms structures. Next, such an approach is applied to explain some successful experiences of industrial policy-making and economic development in Brazil up to the end of the 1970s, and the failures to implement such a policy from the 1980s onwards. Finally, the present government industrial policy is evaluated, arguing that although it has some positive aspects like the focus on innovation, clearly defined targets and a new institutional organization, it fails as an economic development policy because of weaknesses such as incompatibility with macroeconomic policy, inconsistencies of policy instruments, deficiencies in infrastructure and in the science, technology and innovation system, and lack of coordination and political drive.

Sobre a economia política do desenvolvimento e a contribuição dos serviços

On the political economy of development and the contribution of services. This paper aims to ponder on recent approaches to Political Economy of Development, that bring about new concepts about the role of services activities in the economic development process. The analysis begins by checking the new attributions of services entailed by the productive paradigm changes that have occurred since the 1970's. Then, it examines the debate about the new kind of society, called "post-industrial", which is centered in the services dynamics. Finally, it discusses the relevance of social capital disponibility, as a prime factor to attain economic development

Remembering the War and Aggression: A Discourse Analysis of Japan’s State Apologies and Commemoration Speeches on August 15th 1995-2015

Memories of historical injustices affect contemporary politics from local to global level. In East Asia, questions of commemoration and historical responsibility have turned into international and domestic controversies. The main focus has been and still is in apologies conducted by Japanese prime ministers in regards to the war, aggression and colonialism during the era of Imperial Japan. Although it is granted that state apologies are not a crucial part of reconciliation, they can be analysed as a linked but separate process within the context of memory and international relations. The purpose of this study is to examine the discourses of history in Japanese prime ministers’ commemoration speeches on Memorial Ceremony for the War Dead from 1995 to 2015 in order to analyse how the Japanese government is reflecting on its past. In particular, attention is paid on what is being commemorated and how, whether it is the war and its victims or Japan’s post-war era of peace. As an apology is a reciprocal activity, responses from Japan’s most vocal former victims, South Korea and China, were also examined. Discourse analysis was used to identify and examine the different representations of the past. In addition, the apology statements of Japanese prime ministers were analysed in the Many to Many apology framework developed by Tavuchis (1991). Primary material consisted of 21 prime ministers’ speeches from the annual Memorial Ceremony for the War Dead on August 15th and from three apology statements made in 1995, 2005 and 2015. Further international context was primarily collected from newspaper articles of The New York Times and The Times throughout the examined period. It can be concluded from the findings that in the official Japanese remembrance of the past war from 1985’s annexation of Taiwan to the atomic bombings in 1945, both discourses that reinforce apology and remorse over Japan’s past aggressions and discourses that consciously avoid doing so are used. The commemoration speeches and apology statements consistently assert that Japan has acknowledged its past and expresses regret over the acts of aggression. At the same time, the speeches and statements strengthen the narrative that Japan was a victim of circumstances as well as turn the focus on post-war peace-making or on Japan’s own victimhood.

Epistolae Pauli cum glossa ordinaria.

F. 1 Maximes tirées des Pères : « Mulier est caput peccati... » etc. (XIIe et XVIe s.) ; Vers rythmiques : « Vinea culta fuit... » (XVIe s.) (Hervieux, Fabulistes lat., IV, 353). F. 2v Epist. Pauli ad Laodicenses. F. 3 « Divisio prime epistole ad Romanos ». F. 5 XIV. Epist. Pauli, cum glossa ordinaria. F. 187 Note en espagnol relative au prix du blé en 1528 et à un arrêt de la cour de Navarre du 27 nov. 1530. F. 188 Fragm. de grammaire commençant par 4 distiques : « [J]anua sum rudibus... Poeta. Que pars... — ... hec manus, genitivo harum. » (Écriture bolonaise, XIIIe-XIVe s.).

Horae ad usum romanum

F. 1-12v. Calendrier en français, à l’encre rouge et noire, où l’on remarque des formes dialectales picardes et plusieurs saints du Nord : « sainte Audegonde » (30 janvier) ; « le Candelier » (2 févr.) ; « ste Gertrude » (17 mars) ; « saint Quentin » (2 mai) ; « saint Ernoulx » [ep. Suessonensis] (16 août) ; « saint Bertin » (5 septembre) ; « saint Lambert » (17 septembre) ; « saint Franchois » (4 oct.) ; « saint Gillain » [mart. in Hannonia] (16 oct., Ghislain); « le jour st Estievene » (26 déc., rouge). Une deuxième main très cursive ajouté d’autres saints, dont « s. Amand » (6 févr.) ; « s. Waleri » (1er avril) ; « s. Fuscien » [mart. Ambianensis] (27 juin et 10 déc.) ; « s. Firmin » [mart. Ambianensis] (25 septembre) ; « s. Bavon » (1er oct.). F. 13v-17v. « ... hore sancte Crucis». F. 18v-22v. « ... hore de sancto Spiritu ».F. 23v-85. « ... hore beate marie virginis secundum usum romanum ». F. 86v-94v. Office de la Vierge, selon les temps de l’année. « ... officum beate Marie virginis quod dicitur per totum adventum ad vesperas ».F.95-115. « ... septem psalmi penitentiales cum suis litaniis et precibus ». A noter « ... sancte Lamberte... sancte Rumolde [ep. Mechlinensis]... sancte Fursee [ab. Latiniacensis] ... sancte Amande... sancte Vedaste, sancte Bavo... sancte Philiberte... santa Ursula... sancta Brigida... sancta Aldegondis, sancta Gertrudis... ».F.116v-152v. « ... vigilie mortuorum » office des morts à l’usage de Sarum-Normandie-Metz ; cf. K. Ottosen, Responsories..., p. 242 (116v-151). — « Octo versus beati Bernardi ». « Illumina oculos meos ne umquam obdormiam... » ; cf. Leroquais, Livres d’heures, I, XXX-XXXI (151-152v).F.153-158v. « Initium sancti evvangelii secundum Johannem... secundum Lucam... secundum Matheum... secundum Marcum ».F. 158v-166. Suffrages aux saints : « Memoria de santo Johanne Baptista... ; devota oratio... » ; — « ... de sancto Adriano » ; — « ... de sancto Sebastiano » ; — « ... de sancto Anthonio » ; — « ... de sancto Quintino » ; — « ... de sancto Nicholae » ; — « ... de sancto Andrea » ; — « ... de sancto Fiacro ».F.166v-174v. Prières à la Vierge. « ... devotissima oratio ad beatem virginem Mariam ». « O intemerata... O Johannes... » (éd. Wilmart, Auteurs spirituels, 488-490) (166v-169v). — « Alia oratio ad beatam virginem Mariam ». « Obsecro te.... » (éd. Leroquais, Livres d’heures, II, 346-347) (169v-174). Les deux prières sont rédigées à la forme masculine. — « Laus Marie virginis ». « Salve regina... » (Analecta Hymnica, L, 318-319, n° 245) (174-174v). F. 175-184v. Suffrages aux saintes : « ... de santa Barbara » ; — « ... de sancta Margareta » ; — « ... de sancta Katerina » ; — « ... de sancta Maria Magdelena » ; — « ... de sancta Appolonia » ; — « ... de sancta Venicie [Venice, forme dérivée de Véronique] » « Veni sponsa Christi... Versus. Diffusa est gratia... Oratio. Exaudi nos Deus ut sicut de beate Venicie festivitate gaudemus, ita pie devotionis erudiamur. Per.... » ; sur le culte de sainte Véronique/Venice, en particulier à Paris, voir Gr. A. RUNNALS, Le mystère de sainte Venice, Exeter, 1980 (Textes littéraires) (175-180v). — Prières diverses : « ... quinque gaudia de beata virgine Maria » « Gaude Virgo mater Christi... » (éd. Leroquais, Livres d’heures, I, XXVI-XXVII) (180v-182). — « Oratio devota ad Jesum Christum ». « Ave domine Jhesu Christe verbum patris » (éd. Wilmart, Auteurs spirituels, 412 [III]) (182-183). — « Oratio devota que dicitur ad elevationem Domini ». « Ave verum corpus Domini nostri... » (éd. Szövérffy, Die Annalen , II, 298-299) (183-184). — « Memore de saint Miquiel », en latin (184-184v).