Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

UNLABELLED: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. TRIAL REGISTRATION: Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).

Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming.

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.

Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

Early cellular immune response to a new candidate mycobacterial vaccine antigen in childhood tuberculosis

The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes.

Computer modeling of a micro-manufactured one-turn inductor

The results of a finite element computer modelling analysis of a micro-manufactured one-turn magnetic inductor using the software package ANSYS 10.0 are presented. The inductor is designed for a DC-DC converter used in microelectronic devices. It consists of a copper conductor with a rectangular cross-section plated with an insulation layer and a layer of magnetic core. The analysis has focused on the effects of the frequency and the air gaps on the on the inductance values and the Joule losses in the core and conductor. It has been found that an inductor with small multiple air gaps has lower losses than an inductor with a single larger gap

Assessment of microInductors for DC-DC converters

There are increasing demands on the power density and efficiency of DC-DC power converters due to the soaring functionality and operational longevity required for today's electronic products. In addition, DC-DC converters are required to operate at new elevated frequencies in the MHz frequency regime. Typical ferrite cores, whose useable flux density falls drastically at these frequencies, have to be replaced and a method of producing compact component windings developed. In this study, two types of microinductors, pot-core and solenoid, for DC-DC converter applications have been analyzed for their performance in the MHz frequency range. The inductors were manufactured using an adapted UV-LIGA process and included electrodeposited nickel-iron and the commercial alloy Vitrovac 6025 as core materials. Using a vibrating sample magnetometer (VSM) and a Hewlett Packard 4192A LF- impedance analyzer, the inductor characteristics such as power density, efficiency, inductance and Q-factor were recorded. Experimental, finite element and analytical results were used to assess the suitability of the magnetic materials and component geometries for low MHz operation.

Multilevel refinement for combinatorial optimisation: boosting metaheuristic performance

The multilevel paradigm as applied to combinatorial optimisation problems is a simple one, which at its most basic involves recursive coarsening to create a hierarchy of approximations to the original problem. An initial solution is found, usually at the coarsest level, and then iteratively refined at each level, coarsest to finest, typically by using some kind of heuristic optimisation algorithm (either a problem-specific local search scheme or a metaheuristic). Solution extension (or projection) operators can transfer the solution from one level to another. As a general solution strategy, the multilevel paradigm has been in use for many years and has been applied to many problem areas (for example multigrid techniques can be viewed as a prime example of the paradigm). Overview papers such as [] attest to its efficacy. However, with the exception of the graph partitioning problem, multilevel techniques have not been widely applied to combinatorial problems and in this chapter we discuss recent developments. In this chapter we survey the use of multilevel combinatorial techniques and consider their ability to boost the performance of (meta)heuristic optimisation algorithms.

The food multimix concept: new innovative approach to meeting nutritional challenges in Sub-Saharan Africa

Food insecurity, chronic hunger, starvation and malnutrition continue to affect millions of individuals throughout the developing world, especially Sub-Saharan Africa. Various initiatives by African governments and International Agencies such as the UN, the industrial nations, the International Monetary Fund, the World Bank and the World Trade Organisation to boost economic development, have failed to provide the much-needed solution to these challenges. The impact of these economic shifts and the failures of structural adjustment programmes on the nutritional well-being and health of the most vulnerable members of poor communities cannot be over-emphasised. The use of ad hoc measures as an adjunct to community-based rural integrated projects have provided little success and will be unsustainable unless they are linked to harnessing available local resources. The present paper therefore focuses on exploring alternative ways of harnessing the scant agricultural resources by employing a scientific approach to food-related problem-solving. The food multimix (FMM) concept offers a scientific contribution alongside other attempts currently in use by the World Food Programme, WHO and FAO to meet the food insecurity challenges that confront most of the developing world in the twenty-first century. It is an innovative approach that makes better use of traditional food sources as a tool for meeting community nutritional needs. The FMM concept employs a food-based approach using traditional methods of food preparation and locally-available, cheap and affordable staples (fruits, pulses, vegetables and legumes) in the formulation of nutrient-enriched multimixes. Developed recipes can provide >= 40% of the daily nutritional requirements of vulnerable groups, including patients with HIV/AIDS and children undergoing nutrition rehabilitation. The FMM approach can also be used as a medium- to long-term adjunct to community-based rural integration projects aimed at health improvement and economic empowerment in Sub-Saharan Africa.

The Olympic Games and urban displacement: the case of Beijing

Urban spectacles such as the Olympic Games have been long perceived as being able to impose desired effects in the city that act as host. This kind of urban boost may include the creation of new jobs and revenue for local community, growth in tourism and convention business, improvements to city infrastructure and environment, and the stimulation of broad reform in the social, political and institutional realm. Nevertheless at the other end of the debate, the potentially detrimental impacts of Olympic urban development, particularly on disadvantaged and vulnerable groups, have also been increasingly noticed in recent years and subsequently cited by a number of high profile anti-Olympic groups to campaign against Olympic bids and awards. The common areas of concern over Olympic-related projects include the cost and debts risk, environmental threat, the occurrence of social imbalance, and disruption and disturbance of existing community life. Among these issues, displacement of low income households and squatter communities resulting from Olympic-inspired urban renewal are comparatively under-explored and have emerged as an imperative area for research inquiry. This is particularly the case where many other problems have become less prominent. Changing a city’s demographic landscape, particularly displacing lower income people from the area proposed for a profitable development is a highly contentious matter in its own right. Some see it as a natural and inevitable outgrowth of the process of urban evolution, without which cities cannot move towards a more attractive location for consumption-based business. Others believe it reflects urban crises and conflicts, highlighting the market failures, polarization and injustice. Regardless of perception,these phenomena are visible everywhere in post-industrial cities and particularly cannot be ignored when planning for the Olympic Games and other mega-events. The aim of this paper is to start the process of placing the displacement issue in the context of Olympic preparation and to seek a better understanding of their interrelations. In order to develop a better understanding of this issue in terms of cause, process, influential factors and its implication on planning policy, this paper studies the topic from both theoretic and empirical angles. It portrays various situations where the Olympics may trigger or facilitate displacement in host cities during the preparation of the Games, identifies several major variables that may affect the process and the overall outcome, and explores what could be learnt in generic terms for planning Olympic oriented infrastructure so that ill-effects to the local community can be effectively controlled. The paper concludes that the selection of development sites, the integration of Olympic facilities with the city’s fabric, the diversity of housing type produced for local residents and the dynamics of the new socioeconomic structure.

Towards Cloud-Based Knowledge Capturing Based on Natural Language Processing

Paper presented at the Cloud Forward Conference 2015, October 6th-8th, Pisa

Diel rhythmicity in amino acid uptake by Prochlorococcus

The marine cyanobacterium Prochlorococcus, the most abundant phototrophic organism on Earth, numerically dominates the phytoplankton in nitrogen (N)-depleted oceanic gyres. Alongside inorganic N sources such as nitrite and ammonium, natural populations of this genus also acquire organic N, specifically amino acids. Here, we investigated using isotopic tracer and flow cytometric cell sorting techniques whether amino acid uptake by Prochlorococcus is subject to a diel rhythmicity, and if so, whether this was linked to a specific cell cycle stage. We observed, in contrast to diurnally similar methionine uptake rates by Synechococcus cells, obvious diurnal rhythms in methionine uptake by Prochlorococcus cells in the tropical Atlantic. These rhythms were confirmed using reproducible cyclostat experiments with a light-synchronized axenic Prochlorococcus (PCC9511 strain) culture and S-35-methionine and H-3-leucine tracers. Cells acquired the tracers at lower rates around dawn and higher rates around dusk despite > 10(4) times higher concentration of ammonium in the medium, presumably because amino acids can be directly incorporated into protein. Leucine uptake rates by cells in the S+G(2) cell cycle stage were consistently 2.2 times higher than those of cells at the G(1) stage. Furthermore, S+G(2) cells upregulated amino acid uptake 3.5 times from dawn to dusk to boost protein synthesis prior to cell division. Because Prochlorococcus populations can account from 13% at midday to 42% at dusk of total microbial uptake of methionine and probably of other amino acids in N-depleted oceanic waters, this genus exerts diurnally variable, strong competitive pressure on other bacterioplankton populations.

Boosting Blue Growth in a Mild Sea: Analysis of the Synergies Produced by a Multi-Purpose Offshore Installation in the Northern Adriatic, Italy

In the near future, the oceans will be subjected to a massive development of marine infrastructures, including offshore wind, tidal and wave energy farms and constructions for marine aquaculture. The development of these facilities will unavoidably exert environmental pressures on marine ecosystems. It is therefore crucial that the economic costs, the use of marine space and the environmental impacts of these activities remain within acceptable limits. Moreover, the installation of arrays of wave energy devices is still far from being economically feasible due to many combined aspects, such as immature technologies for energy conversion, local energy storage and moorings. Therefore, multi-purpose solutions combining renewable energy from the sea (wind, wave, tide), aquaculture and transportation facilities can be considered as a challenging, yet advantageous, way to boost blue growth. This would be due to the sharing of the costs of installation and using the produced energy locally to feed the different functionalities and optimizing marine spatial planning. This paper focuses on the synergies that may be produced by a multi-purpose offshore installation in a relatively calm sea, i.e., the Northern Adriatic Sea, Italy, and specifically offshore Venice. It analyzes the combination of aquaculture, energy production from wind and waves, and energy storage or transfer. Alternative solutions are evaluated based on specific criteria, including the maturity of the technology, the environmental impact, the induced risks and the costs. Based on expert judgment, the alternatives are ranked and a preliminary layout of the selected multi-purpose installation for the case study is proposed, to further allow the exploitation of the synergies among different functionalities.

An Experimental and Predictive Evaluation of Unsteady Gas Flow through Automotive Catalyst Elements

The incorporation of one-dimensional simulation codes within engine modelling applications has proved to be a useful tool in evaluating unsteady gas flow through elements in the exhaust system. This paper reports on an experimental and theoretical investigation into the behaviour of unsteady gas flow through catalyst substrate elements. A one-dimensional (1-D) catalyst model has been incorporated into a 1-D simulation code to predict this behaviour.

Experimental data was acquired using a ‘single pulse’ test rig. Substrate samples were tested under ambient conditions in order to investigate a range of regimes experienced by the catalyst during operation. This allowed reflection and transmission characteristics to be quantified in relation to both geometric and physical properties of substrate elements. Correlation between measured and predicted results is demonstrably good and the model provides an effective analysis tool for evaluating unsteady gas flow through different catalytic converter designs.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose–volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7–31.2% depending on the /ß ratio of prostate cancer (p

The training in social and solidarity economy. Analysis of the university offer in Spain

This research analyses the importance of the training for the promotion of the social economy in two ways: 1) focusing on the characteristics of the educational offer of Social Economy and 2) analyzing its differences regarding to those studies from the Management, entrepreneurship, and innovations areas. To this aim, it is carried out as a first step a literature review of the contributions that study the relationships that can exist between the education and Economy. Then, being based on this previous analysis, we already center our research on the Social Economy sector and its relations with the education system. To get this objective, it has been developed a database that includes all the postgraduate titles related to the Economics area. Likewise, a questionnaire has been designed with the aim of characterize the training in social Economy. As a conclusion, it is obtained that the training in social economy in postgraduate studies in the Spanish Universities is very poor. On the other hand, there are significant differences between Social Economy degrees and Business Management, entrepreneurship and innovation degrees with regard to different aspects such as: values to transmit, competencies, skills, the way of understanding the Economy, etc. Based on these conclusions, different recommendations are proposed in order to promote and boost this other way of doing Economy through the training and education in postgraduate studies.