Challenges in the research and development of new human vaccines

The field of vaccinology was born from the observations by the fathers of vaccination, Edward Jenner and Louis Pasteur, that a permanent, positive change in the way our bodies respond to life-threatening infectious diseases can be obtained by specific challenge with the inactivated infectious agent performed in a controlled manner, avoiding the development of clinical disease upon exposure to the virulent pathogen. Many of the vaccines still in use today were developed on an empirical basis, essentially following the paradigm established by Pasteur, “isolate, inactivate, and inject” the disease-causing microorganism, and are capable of eliciting uniform, long-term immune memory responses that constitute the key to their proven efficacy. However, vaccines for pathogens considered as priority targets of public health concern are still lacking. The literature tends to focus more often on vaccine research problems associated with specific pathogens, but it is increasingly clear that there are common bottlenecks in vaccine research, which need to be solved in order to advance the development of the field as a whole. As part of a group of articles, the objective of the present report is to pinpoint these bottlenecks, exploring the literature for common problems and solutions in vaccine research applied to different situations. Our goal is to stimulate brainstorming among specialists of different fields related to vaccine research and development. Here, we briefly summarize the topics we intend to deal with in this discussion.

An animal experimental study of porous magnesium scaffold degradation and osteogenesis

Our objective was to observe the biodegradable and osteogenic properties of magnesium scaffolding under in vivo conditions. Twelve 6-month-old male New Zealand white rabbits were randomly divided into two groups. The chosen operation site was the femoral condyle on the right side. The experimental group was implanted with porous magnesium scaffolds, while the control group was implanted with hydroxyapatite scaffolds. X-ray and blood tests, which included serum magnesium, alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were performed serially at 1, 2, and 3 weeks, and 1, 2, and 3 months. All rabbits were killed 3 months postoperatively, and the heart, kidney, spleen, and liver were analyzed with hematoxylin and eosin (HE) staining. The bone samples were subjected to microcomputed tomography scanning (micro-CT) and hard tissue biopsy. SPSS 13.0 (USA) was used for data analysis, and values of P<0.05 were considered to be significant. Bubbles appeared in the X-ray of the experimental group after 2 weeks, whereas there was no gas in the control group. There were no statistical differences for the serum magnesium concentrations, ALT, BUN, and CREA between the two groups (P>0.05). All HE-stained slices were normal, which suggested good biocompatibility of the scaffold. Micro-CT showed that magnesium scaffolds degraded mainly from the outside to inside, and new bone was ingrown following the degradation of magnesium scaffolds. The hydroxyapatite scaffold was not degraded and had fewer osteoblasts scattered on its surface. There was a significant difference in the new bone formation and scaffold bioabsorption between the two groups (9.29±1.27 vs 1.40±0.49 and 7.80±0.50 vs 0.00±0.00 mm3, respectively; P<0.05). The magnesium scaffold performed well in degradation and osteogenesis, and is a promising material for orthopedics.

Invoice process analysis and development. Case: Power and automation technology company

This master’s thesis studies the case company’s current purchase invoice process and the challenges that are related to it. Like most of other master’s thesis this study consists of both theoretical- and empirical parts. The purpose of this work is to combine theoretical and empirical parts together so that the theoretical part brings value to the empirical case study. The case company’s main business is frequency converters for both low voltage AC & DC drives and medium voltage AC Drives which are used across all industries and applications. The main focus of this study is on the current invoice process modelling. When modelling the existing process with discipline and care, current challenges can be understood better. Empirical study relays heavily on interviews and existing, yet fragmented, data. This, along with own calculations and analysis, creates the foundation for the empirical part of this master’s thesis.

Effects of grilling on cholesterol oxide formation and fatty acids alterations in fish

Due to the adverse effects of the cholesterol oxidation products for the human health, the search of the occurrence and the quantification of these compounds in foods are considered of great importance. In this paper the effect of grilling in hake and sardine on cholesterol oxides formation and fatty acids alterations was investigated. The main fatty acids determined in both fishes were docosahexaenoic (DHA), oleic, eicosapentaenoic (EPA) and palmitoleic. The total lipids, fatty acids and cholesterol contents were decreased significantly (p < 0.02) after thermal treatment, with simultaneous increase of the cholesterol oxides contents. The cholesterol oxides determined in both species in the present study were: 19-hydroxycholesterol, 24(S)-hydroxycholesterol, 22(S) hydroxycholesterol, 25-hydroxycholesterol, 25(R)-hydroxycholesterol and 7-ketocolesterol. Besides the presence of the cholesterol oxides in raw fishes, there were a greater number of products resulting from the oxidation of cholesterol side chain, a fact rarely observed in foods.

Characterization and development of marolo (Annona crassiflora, Mart.)

The objectives of this study was the physical, chemical, and physiological characterization of marolo (Annona crassiflora, Mart.) during its development. The fruits were harvested 12 Km off Itumirim, Southern Minas Gerais, Brazil, at 20-d intervals from anthesis to fruit maturity. The first fruits were harvested within 60 days. The total development of the fruit took 140 days starting from anthesis. At 140 days after anthesis, the fruit reached its maximum size, with mass of 1.380g, transverse diameter of 13.0 cm, and longitudinal diameter of 11.5 cm. During its development, the fruit showed increase in mass and in traverse and longitudinal diameters. The changes during maturation and ripening, such as: pH reduction and starch degradation, pectic solubilization, and increase in total sugars, soluble solids (ºB), respiratory rate (CO2), titratable acidity, vitamin C, and β-caroteno were observed from the 120th day of marolo development. A decrease in ability to sequester free radicals was observed up the 120th day, followed by an increase. The volatile compounds identified at the end of the development included the esters group only.

Phisicochemical, sensory, and microbiological evaluation and development of symbiotic fermented drink

The goal of this study was to develop a symbiotic lacteous drink, evaluate its physicochemical and sensory characteristics, and verify the viability of Lactobacillus acidophilus in the drink. The milk serum-based drink consisted of 50% milk serum containing 10% saccharose, 25% powdered milk, 15% yacon pulp, and cultures of Lactobacillus acidophilus-La 5E and Bifidobacterium bifidum BB12. It was stored for up to 21 days under refrigeration. The milk serum-based drink was analyzed for protein, ether extract, total dietary fiber, total frutans, carbohydrate content, color, pH, acidity, and contamination by coliforms, and Salmonella sp. Coliforms and Salmonella sp were not detected, and L. acidophilus and B. bifidum provided satisfactory probiotic counts up to 21 days of storage under refrigeration. Lactobacillus acidophilus resistance to gastric acids and bile salts was detected only up to seven days of storage when evaluated in vitro. Sensory analysis and purchase viability were evaluated by consumers at 0, 7, 14, and 21 days of storage. Based on the analytical results and consumer evaluation, the drink was acceptable up to seven days of storage.

Knowledge governance, innovation and development

This paper aims to be a very preliminary effort to contribute to a better understanding of the interaction among innovation, competition and intellectual property policies from an evolutionary-developmental perspective. As such, it seeks to build a more coherent framework within which the discussions of both institution building and policy design for development can proceed. In order to accomplish that, the paper introduces the concept of "Knowledge Governance" as an alternative analytical and policy-oriented approach, and suggests that from a public policy/public interest perspective, and within an evolutionary framework, it is a better way to address the problems concerning the production, appropriability and diffusion of knowledge. In doing so, it also intends contribute to broaden the ongoing discussions on the "New Developmentalism".

Education and development projects in Brazil (1932-2004): political economy perspective

This paper discusses the long-run history of education policies in Brazil. It is suggested that the main reason for the educational backwardness was the existence of strong political interests over education. It is also defended that these interests can be empirically observed in the allocation of public resources between the different levels of education, with political choices favouring specific groups in society. It was not a matter of lack of investment in education, but of inadequate allocation of resources. This pattern of political-based policies created a strong negative path dependence of misallocation of resources in education in Brazil, particularly with significant underinvestment in secondary education.

Autonomy of the state and development in the democratic capitalism

The paper argues that if the state, as an expression and part of a pact of domination, operates as a corporate actor with relative autonomy, vision and capacity to promote the development, it is a key institution to the economic transformation. Supported in the neo-Marxism, exposes the limits of institutionalist approach of autonomy of the state to explain its origin, but does not rule out this approach. Maintains that the class-balance theory of the state may explain its relative autonomy and at the same time aid in understanding the historical experiences of social-developmentalist state action, particularly in the social democratic regimes and in the current Latin America.

Public management, policy capacity, innovation and development

In this paper we discuss the question of what factors in development policy create specific forms of policy capacity and under what circumstances developmentoriented complementarities or mismatches between the public and private sectors emerge. We argue that specific forms of policy capacity emerge from three interlinked policy choices, each fundamentally evolutionary in nature: policy choices on understanding the nature and sources of technical change and innovation; on the ways of financing economic growth, in particular technical change; and on the nature of public management to deliver and implement both previous sets of policy choices. Thus, policy capacity is not so much a continuum of abilities (from less to more), but rather a variety of modes of making policy that originate from co-evolutionary processes in capitalist development. To illustrate, we briefly reflect upon how the East Asian developmental states of the 1960s-1980s and Eastern European transition policies since the 1990s led to almost opposite institutional systems for financing, designing and managing development strategies, and how this led, through co-evolutionary processes, to different forms of policy capacity.

Is GABA involved in regulating plant growth and development? /

Rapid and large accumulation of GABA (y-aminobutyric acid) in response to a number of plant stresses has been well documented. But the role(s) of GABA in plants is not well defined. In recent years, the possibility of GABA involvement in regulating plant growth and development has been raised. In the present study, this possibility was examined. First, to rapidly and accurately determine GABA levels in plant tissues, a spectrometric method for GABA determination was developed based on a commercially available enzyme Gabase. Seventy mM LaCb almost completely removed water-soluble pigments from plant tissues which greatly interfere with the absorbance reading at 340nm. Inactivation of GAD (glutamate decarboxylase) by immediately adding methanol to a frozen plant tissue powder was suggested to prevent GABA production during extraction. The recovery of GABA with this method was approximately 100%. Second, the relationship between GABA levels and hypocotyl elongation in soybean seedlings was analyzed using different approaches to regulate in vivo GABA levels and the elongation of hypocotyls. The following major observations were made. (1) Mechanical stimulation by stroking elevated GABA levels and concurrently induced a rapid and significant reduction in hypocotyl elongation. (2) External GABA was demonstrated to penetrate into the hypocotyls using '*C-GABA. Application of external GABA elevated in vivo GABA levels, but failed to inhibit hypocotyl elongation. (3) LaCla and blue light irradiation caused an inhibition in the elongation of dark-grown hypocotyls, whereas GABA levels were not significantly affected. (4) Ca^was suggested to be involved in the signal transduction pathway leading from mechanical stimulation to GABA production, as indicated by the ability of La'* to inhibit GABA production in stimulated hypocotyls. (5) Bicuculline, saclofen and baclofen (agonists and antagonists of GABA receptors in animals) had no effect on hypocotyl elongation. It might indicate that GABA-binding components which are structurally similar to animal GABA receptors and functionally capable of regulating plant growth may not exist in plants. Therefore, the conclusion was drawn that GABA alone is not sufficient to inhibit hypocotyl elongation. Third, chloride influx in isolated Asparagus cells was enhanced by lOmM GABA during a 3 hour incubation, but the effect was not specific for GABA. Chloride efflux was not influenced by GABA. Both influx and efflux of chloride were significantly inhibited by NPPB, a chloride channel blocker. These results suggest that GABA does not influence the activity of plant chloride channels.