HIV-1/AIDS vaccines must address the extreme diversity of HIV-1. We have designed new polyvalent vaccine antigens comprised of sets of 'mosaic' proteins, assembled from fragments of natural sequences ...via a computational optimization method. Mosaic proteins resemble natural proteins, and a mosaic set maximizes the coverage of potential T-cell epitopes (peptides of nine amino acids) for a viral population. We found that coverage of viral diversity using mosaics was greatly increased compared to coverage by natural-sequence vaccine candidates, for both variable and conserved proteins; for conserved HIV-1 proteins, global coverage may be feasible. For example, four mosaic proteins perfectly matched 74% of 9-amino-acid potential epitopes in global Gag sequences; 87% of potential epitopes matched at least 8 of 9 positions. In contrast, a single natural Gag protein covered only 37% (9 of 9) and 67% (8 of 9). Mosaics provide diversity coverage comparable to that afforded by thousands of separate peptides, but, because the fragments of natural proteins are compressed into a small number of native-like proteins, they are tractable for vaccines.
Summary
This review describes and discusses the structure, biosynthesis and applications of exopolysaccharides from lactic acid bacteria. These substances are classified as homopolysaccharides, which ...are synthesised from sucrose through the action of extracellular glycosyltransferases or heteropolysaccharides, which are synthesised from repeating unit precursors formed in the cytoplasm and assembled extracellularly by the sequential addition of nucleotide sugars. The industrial application of exopolysaccharides is linked to enhancing the texture and rheological properties of certain fermented products and their production in situ being of particular interest. The chemical characteristics of exopolysaccharides influence interactions with milk proteins in fermented dairy products. These compounds reduce gel syneresis and increase the viscosity, water retention capacity and firmness of the gel, all of which are desirable characteristics for the development of low‐fat dairy products. Similarly, they have applications in the production of gluten‐free bakery products and fermented meat products.
Main differences between the exopolysaccharides produced by lactic acid bacteria and its main applications in fermented foods.
The Power of Design Reinders, Angele; Brezet, Han; Diehl, Jan Carel
2012, 2012., 2013/01/01, 2012-11-28T00:00:00, 2012-09-25
eBook
The Power of Designoffers an introduction and a practical guide to product innovation, integrating the key topics that are necessary for the design of sustainable and energy-efficient products using ...sustainable energy technologies.Product innovation in sustainable energy technologies is an interdisciplinary field. In response to its growing importance and the need for an integrated view on the development of solutions, this text addresses the functional principles of various energy technologies next to the latest design processes and innovation methods.From the perspective of product applications, the book provides clear explanations of technologies that are significant for product integration, such as batteries, photovoltaic solar energy, fuel cells, small wind turbines, human power, energy saving lighting, thermal energy technologies in buildings, and piezoelectric energy conversions. The design processes and innovation methods presented in this book include various approaches ranging from technical, societal and creative methods that can be applied in different stages of the design process.Other features include:a methodological approach, enabling readers to easily apply the theory to their research projects and to the actual design of sustainable products with energy technologiesdiscussion on interaction design and smart grid interventionscolour photographs that illustrate the final productsnumerous case studies of product development projects and concepts in practice, enabling readers to understand and design energy-efficient products in several different marketsa companion website containing useful information about the cases and an additional design cases with sustainable energy technologiesThe Power of Design provides a comprehensive and visually-appealing opening into the subject for third and fourth year students, postgraduates, and professionals in the areas of energy, environment, product design and engineering
Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural ...products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.
This review summarizes the four processes of wound healing in the human body (hemostasis, inflammatory, proliferation, and remodeling) and the most current research on the most important factors ...affecting cutaneous wound healing and the underlying cellular and/or molecular pathways. Local factors, including temperature, oxygenation, and infection, and systemic factors, such as age, diabetes, sex hormones, genetic components, autoimmune diseases, psychological stress, smoking and obesity are also addressed. A better understanding of the role of these factors in wound repair could result in the development of therapeutics that promote wound healing and resolve affected wounds. Additionally, natural products obtained from plants and animals are critical targets for the discovery of novel biologically significant pharmacophores, such as medicines and agrochemicals. This review outlines the most recent advances in naturally derived targeted treatment for wound healing. These are plant-derived natural products, insect-derived natural products, marine-derived natural products, nanomaterial-based wound-healing therapeutics (metal- and non-metal-based nanoparticles), and natural product-based nanomedicine to improve the future direction of wound healing. Natural products extracted from plants and animals have advanced significantly, particularly in the treatment of wound healing. As a result, the isolation and extraction of bioactive compounds from a variety of sources can continue to advance our understanding of wound healing. Undescribed bioactive compounds or unexplored formulations that could have a role in today's medicinal arsenal may be contained in the abundance of natural products and natural product derivatives.
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Dietary advanced glycation end products (AGE) formed during heating of food have gained interest as potential nutritional toxins with adverse effects on inflammation and glucose metabolism. In the ...present study, we investigated the short-term effects of high and low molecular weight (HMW and LMW) dietary AGE on insulin sensitivity, expression of the receptor for AGE (RAGE), the AGE receptor 1 (AGER1) and TNF-α, F2-isoprostaglandins, body composition and food intake. For 2 weeks, thirty-six Sprague–Dawley rats were fed a diet containing 20 % milk powder with different proportions of this being given as heated milk powder (0, 40 or 100 %), either native (HMW) or hydrolysed (LMW). Gene expression of RAGE and AGER1 in whole blood increased in the group receiving a high AGE LMW diet, which also had the highest urinary excretion of the AGE, methylglyoxal-derived hydroimidazolone 1 (MG-H1). Urinary excretion of N
ε
-carboxymethyl-lysine increased with increasing proportion of heat-treated milk powder in the HMW and LMW diets but was unrelated to gene expression. There was no difference in insulin sensitivity, F2-isoprostaglandins, food intake, water intake, body weight or body composition between the groups. In conclusion, RAGE and AGER1 expression can be influenced by a high AGE diet after only 2 weeks in proportion to MG-H1 excretion. No other short-term effects were observed.
Making in America Berger, Suzanne; MIT Task Force on Production in the Inno, M. I. T. Task
08/2013
eBook
America is the world leader in innovation, but many of the innovative ideas that are hatched in American start-ups, labs, and companies end up going abroad to reach commercial scale. Apple, the ...superstar of innovation, locates its production in China (yet still reaps most of its profits in the United States). When innovation does not find the capital, skills, and expertise it needs to come to market in the United States, what does it mean for economic growth and job creation? Inspired by the MIT Made in America project of the 1980s,Making in Americabrings experts from across MIT to focus on a critical problem for the country.MIT scientists, engineers, social scientists, and management experts visited more than 250 firms in the United States, Germany, and China. In companies across America--from big defense contractors to small machine shops and new technology startups--these experts tried to learn how we can rebuild the industrial landscape to sustain an innovative economy. At each stop, they asked this basic question: "When you have a new idea, how do you get it into the market?" They found gaping holes and missing pieces in the industrial ecosystem. Critical strengths and capabilities that once helped bring new enterprises to life have disappeared: production capacity; small and medium-size suppliers; spillovers of research, training, and new technology from big corporations. (Production in the Innovation Economy, also published by the MIT Press in 2013, describes this research.)Even in an Internet-connected world, proximity to innovation and users matters for industry.Making in Americadescribes ways to strengthen this connection, including public-private collaborations, new government-initiated manufacturing innovation institutes, and industry-community college projects. If we can learn from these ongoing experiments in linking innovation to production, American manufacturing could have a renaissance.
Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and ...personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data Sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed Initially, were solicited from academic government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data Synthesis: The top 20 priority questions fell into seven categories: a) prioritization or substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.
Macrocyclic natural products have evolved to fulfil numerous biochemical functions, and their profound pharmacological properties have led to their development as drugs. A macrocycle provides diverse ...functionality and stereochemical complexity in a conformationally pre-organized ring structure. This can result in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular locations. Despite these valuable characteristics, and the proven success of more than 100 marketed macrocycle drugs derived from natural products, this structural class has been poorly explored within drug discovery. This is in part due to concerns about synthetic intractability and non-drug-like properties. This Review describes the growing body of data in favour of macrocyclic therapeutics, and demonstrates that this class of compounds can be both fully drug-like in its properties and readily prepared owing to recent advances in synthetic medicinal chemistry.
The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB) boosted by a recombinant adenovirus serotype-5 (rAd5) HIV-1 with ...matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean.
480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector) at 0, 1 and 2 months, followed by rAd5 (10(10) PU i.m. by needle/syringe) at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost.
The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ) ELISpot to global potential T-cell epitopes (PTEs) were observed in 70.8% (136/192) of vaccine recipients overall, most frequently to Gag (54.7%) and to Env (54.2%). In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035). The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively) and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6%) of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients.
The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies.
ClinicalTrials.gov NCT00125970.