Simplified Monopalmitoyl Toll-like Receptor 2 Ligand Mini-UPam for Self-Adjuvanting Neoantigen-Based Synthetic Cancer Vaccines

Synthetic vaccines, based on antigenic peptides that comprise MHC−I and MHC-II T-cell epitopes expressed by tumors, show great promise for the immunotherapy of cancer. For optimal immunogenicity, the synthetic peptides (SPs) should be adjuvanted with suitable immunostimulatory additives. Previously, we have shown that improved immunogenicity in vivo is obtained with vaccine modalities in which an SP is covalently connected to an adjuvanting moiety, typically a ligand to Toll-like receptor 2 (TLR2). SPs were covalently attached to UPam, which is a derivative of the classic TLR2 ligand Pam₃CysSK₄. A disadvantage of the triply palmitoylated UPam is its high lipophilicity, which precludes universal adoption of this adjuvant for covalent modification of various antigenic peptides as it renders the synthetic vaccine insoluble in several cases. Here, we report a novel conjugatable TLR2 ligand, mini-UPam, which contains only one palmitoyl chain, rather than three, and therefore has less impact on the solubility and other physicochemical properties of a synthetic peptide. In this study, we used SPs that contain the clinically relevant neoepitopes identified in a melanoma patient who completely recovered after T-cell therapy. Homogeneous mini-UPam-SP conjugates have been prepared in good yields by stepwise solid-phase synthesis that employed a mini-UPam building block pre-prepared in solution and the standard set of Fmoc-amino acids. The immunogenicity of the novel mini-UPam-SP conjugates was demonstrated by using the cancer patient's T-cells.     

Anaerobic treatment of wastes containing methanol and higher alcohols

Experiments have been performed to ascertain the feasibility of anaerobic digestion for the treatment of an alcoholic waste (i.e. fusel oil), consisting of approx. 50% methanol and 50% higher alcohols. Batch experiments as well as continuous experiments have been conducted. The continuous experiments have been carried out using the “Upflow Anaerobic Sludge Blanket” (UASB-) process. As inoculum a sugar beet waste grown and highly settleable and active anaerobic sludge (SBA-sludge) has been used. The SBA-sludge was shown to be superior to digested sewage sludge as seed material for an anaerobic treatment process, because—although it in fact is adapted to the fermentation of volatile fatty acids (VFA)—it does not have any significant difficulty with respect to the methanogenesis of the alcohols present in the fusel oil waste. The breakdown of higher alcohols starts immediately and that of methanol within a few days, depending on the initial load applied. In the UASB-experiments sludge loads up to 0.6 kg COD·kg VSS⁻¹·day⁻¹ could already be well accommodated within 1 week, so that within this period a space load could be handled as high as 20 kg COD·m⁻³·day⁻¹, simply by supplying the reactor with approx. 30 kg SBA-VSS·m⁻³ averaged over the total reactor volume.Contrary to recent findings of Smith & Mah (Appl. envir. Microbial. 36, 870–879, 1978), which were obtained with a pure culture of Methanosarcina barkeri, the sludge is capable of fermenting VFA and methanol rapidly and simultaneously, provided the conditions for VFA and methanol fermentation are favourable. However, as in previous experiments with aqueous solutions of methanol (Lettinga et al., Water Res. 13, 725–737, 1979), we observed that the digestion process can easily become upset, especially with respect to the degradation of VFA. Once again indications have been obtained that one or more trace elements are of eminent importance with respect to the stability of the process. At present the operation of a stable anaerobic treatment process for methanolic wastes cannot be guaranteed.     

3D Virtual Pome Fruit Tissue Generation Based on Cell Growth Modeling

A 3D virtual fruit tissue generator is presented that can distinctly define the microstructural components of a fruit tissue and that can be used to model important physical processes such as gas transport during controlled atmosphere storage. The model is based on the biomechanics of plant cells in tissues. The main merit of this algorithm is that it can account for typical differences in intercellular air space networks and in cell size and shape found between different fruit species and tissues. The cell is considered as a closed thin walled structure, maintained in tension by turgor pressure. The cell walls of adjacent cells are modeled as parallel, linear elastic elements which obey Hooke's law. A 3D Voronoi tessellation is used to generate the initial topology of the cells. Intercellular air spaces of schizogenous origin are generated by separating the Voronoi cells along the edges where three Voronoi cells are in contact; while intercellular air spaces of lysigenous origin are generated by deleting (killing) some of the Voronoi cells randomly. Cell expansion then results from turgor pressure acting on the yielding cell wall material. To find the sequence of positions of each vertex and thus the shape of the tissue with time, a system of differential equations for the positions and velocities of each vertex is established and solved using a Matlab ordinary differential equation solver. Statistical comparison with synchrotron tomography images of fruit tissue is excellent. The virtual tissues can be used to study tissue mechanics and exchange processes of important metabolites.     

A Multiphase Pore Scale Network Model of Gas Exchange in Apple Fruit

A multiphase pore scale network model was developed to describe mass transfer in apple fruit. The 3D microscale geometry of the tissue was reconstructed from synchrotron radiation tomography images. Individual cells and pores were identified using a watershed segmentation procedure on a Euclidean distance map of the tissue microstructure. Further morphological characteristics of each individual pore, including its volume, connections to the neighbors and the connected area between the pore and its neighbors, were determined. The tissue was represented by a network of nodes (simplified individual pores and cells) that were interconnected by tubes. The transport of the respiratory gases O₂ and CO₂ between two nodes was modelled using diffusion laws and irreversible thermodynamics, while respiration was taken into account in the individual cellular nodes. A numerical procedure was applied to simulate the gas transport within the discrete network and to compute the local diffusivities of the links in the network. The predicted overall gas diffusivities compared well to experimental data and results computed from a microscale continuum model, thereby validating the pore scale network model. This approach is a computationally attractive alternative to a continuum multiphase approach for modelling gas transport in fruit.     

The Brazilian experience of rural electrification in the Amazon with decentralized generation - The need to change the paradigm from electrification to development

There are at least 607 thousand households in the Brazilian Amazon that need to be attended with some form of regular electricity service. These households are not attended by the electricity sector through its electricity distribution companies and most of them have some form of precarious decentralized electricity generation that is not registered or regulated in the institutional framework. Diverse initiatives were taken by Brazilian government to attend these household through alternatives that relied on locally available renewable energy. This paper accesses this initiatives of rural electrification in the Brazilian Amazon. First an overview of the problems of rural electricity are discussed and its specificities in the Brazilian Amazon. Then the Brazilian institutional framework that organizes the decentralized electricity generation is described with its various limitations. The diverse initiatives undertaken to attend the rural communities in the Amazon since the 1990s are described, as well as how these initiatives are linked to the policies for rural electrification. The results shows that it can be inferred that sole market mechanisms are not sufficient to guarantee economic sustainability of these projects. This can be one of the reasons why traditional electricity distribution companies showed the lack of interest in promoting rural electrification with other means than grid extension. The most successful projects had financed efforts to integrate the generation of electricity into local development initiatives in order to guarantee sustainability and used substantial part of funding for local mobilization and organization. It needs a paradigm chance by treating these initiatives as local development initiatives and promoting alternative ways for its implementation through partnership between local new actors in the electricity sector and government and implementing policy on a local municipal level.     

Suitability of European climate for the Asian tiger mosquito Aedes albopictus: recent trends and future scenarios

The Asian tiger mosquito (Aedes albopictus) is an invasive species that has the potential to transmit infectious diseases such as dengue and chikungunya fever. Using high-resolution observations and regional climate model scenarios for the future, we investigated the suitability of Europe for A. albopictus using both recent climate and future climate conditions. The results show that southern France, northern Italy, the northern coast of Spain, the eastern coast of the Adriatic Sea and western Turkey were climatically suitable areas for the establishment of the mosquito during the 1960–1980s. Over the last two decades, climate conditions have become more suitable for the mosquito over central northwestern Europe (Benelux, western Germany) and the Balkans, while they have become less suitable over southern Spain. Similar trends are likely in the future, with an increased risk simulated over northern Europe and slightly decreased risk over southern Europe. These distribution shifts are related to wetter and warmer conditions favouring the overwintering of A. albopictus in the north, and drier and warmer summers that might limit its southward expansion.     

徘徊的残像——Ben van Berkel访谈录

BenvanBerkel曾就读于阿姆斯特丹Rietveld学院和伦敦建筑协会建筑学院（AA）。1988年．他和艺术历史学家CarolineBos共同创立了UNStudio。1996年。他参与鹿特丹知名的伊拉斯谟大桥的外形设计。这深刻地影响了他对当代建筑的理解．从而形成自己独具一格的风格。亦成为UNStudio营运理念的基础。BenvanBerkeI在许多知名的大学担任过客座讲师。与他人合作撰写了大量论文和专著。BenvanBerkel目前是德国法兰克福StaedeIschule概念设计系的教授和建筑学院院长。而他在中国的第一个项目，已开始在杭州建设。     

Approaches to atomistic triple-line properties from first-principles

Different approaches to study wetting and adhesion by applying density-functional theory (DFT) methods are highlighted. The ab initio thermodynamics method is used to demonstrate the link between the calculated work of separation and the work of adhesion and wetting angles from sessile-drop measurements. An approach to extend DFT calculations to the case of large-scale interfaces relevant for wetting systems is also discussed.     

Research-by-design framework for integrating education and research in an intercultural parallel design studio

Intercultural student exchange can positively impact education, research, and society. Research-by-design has been put forward in design education as an approach to explicitly address the integration of education and research. The problem is that design schools develop their own interpretation of this approach, which brings difficulty in virtually comparing and learning from the generated design proposals. This case is evident in intercultural parallel design studios that deal with diverging socio-cultural and institutional traditions. In addressing this problem and maximizing the benefits of intercultural exchange, this study proposes to adopt a meta perspective and use the design as co-evolution model as a framework for analyzing and comparing design data generated by different research-by-design approaches. The study applies this meta perspective on an intercultural architectural design studio jointly organized by Ton Duc Thang University (Vietnam) and Hasselt University (Belgium).