Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside

Non-viral gene delivery vectors are emerging as a safer alternative to viral vectors. Among natural polymers, chitosan (Ch) is the most studied one, and low molecular weight Ch, specifically, presents a wide range of advantages for non-viral pDNA delivery. It is crucial to determine the best process for the formation of Low Molecular Weight Chitosan (LMWC)-pDNA complexes and to characterize their physicochemical properties to better understand their behavior once the polyplexes are administered. The transfection efficiency of Ch based polyplexes is relatively low. Therefore, it is essential to understand all the transfection process, including the cellular uptake, endosomal escape and nuclear import, together with the parameters involved in the process to improve the design and development of the non-viral vectors. The aim of this review is to describe the formation and characterization of LMWC based polyplexes, the in vitro transfection process and finally, the in vivo applications of LMWC based polyplexes for gene therapy purposes.

The patents in the introduction of reinforced concrete in Spain: "Alhondiga de Bilbao" case study

Reinforced concrete structures are introduced in Spain mainly by French influence. This happens in the late nineteenth century, following the scheme operating through proprietary systems prevailing in Europe. Systems initially have poor scientific support reaching, even early twentieth century, an impediment to the development of concrete structures, due to the lack of knowledge shown, as well as due to a series of accidents. Therefore, from the end of the first decade of the past century are enacted a series of regulations in many countries, that will change the design and calculation of reinforced concrete structure. The knowledge of the environment of the patent systems, its beginnings and the circumstances of their application allow us to understand the constraints of the early concrete structures, as presented in the Bilbao wine store (1906).

The laser-assisted cold spray process

Thick metal coatings are currently deposited via two well established routes, Laser or arc based cladding, and thermal spray. A new coating technique known as Laser-assisted Cold Spray (LCS), which aims to expand on the capabilities of the two process routes currently available, is under development at the University of Cambridge in the UK. LCS is a development of the Cold Spray process (CS) in which coatings are built up from powder particles which are entrained within a gas stream and accelerated through a de Laval nozzle, impacting the substrate at supersonic speeds that exceed a material dependent critical velocity.

D. Rodrigo de Souza Coutinho e o reformismo ilustrado: manutenção e exploração da América portuguesa no final do século XVIII

A dissertação busca demonstrar como o final do século XVIII português foi marcado por tentativas de estabelecimento de programas de reformas pautadas em estratégias reformistas, no sentido de salvar Portugal da difícil situação social, política econômica em que o mesmo se encontrava. Nesse sentido, destaca a administração de D. Rodrigo de Souza Coutinho, ministro da marinha e do ultramar e teórico da Ilustração luso-brasileira, que teve como proposta manter e explorar a América portuguesa, baseado no mercantilismo ilustrado. A dissertação destaca, ainda, o papel da Academia Real das Ciências de Lisboa, reduto da intelectualidade luso-brasileira, cujo auxílio permitiu que fosse colocada em prática uma exploração renovada e útil das riquezas do Brasil, calcada no ideal de reforma das Luzes.

From the Cajal alumni Achucarro and Rio-Hortega to the rediscovery of never-resting microglia

Under the guidance of Ramon y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolas Achucarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pio del Rio-Hortega developed modifications of Achucarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called "third element" of the nervous system), leading to a long-standing discussion. It was only in 1924 that Rio-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely "resting," and their contribution as "activated" cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: "resting" microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their causal relationship to diseases.

Laser slotting: a new laser machining technique

This work describes a new technique for the selective removal of steel using a conventional CO2 laser beam and a novel arrangement of inert and reactive gas jets to produce the gas equivalent of a rotary cutter.

中国野青茅属的分类学修订

　　通过野外观察和标本研究，本文分析了中国野青茅属植物主要形态性状的变异式样，对其叶片表皮进行了光镜和电镜观察，对外稃表皮进行了电镜观察，分析了该属植物的生态和地理分布。在此基础上，对中国野青茅属植物进行了分类修订。 1．形态性状分析 分析结果显示：野青茅属植物形态变异极其复杂，性状之间大多缺少相关性，属内有分类价值的性状较为贫乏。一般来说，颖片表面特征、基盘毛与外稃的相对长度、外稃的质地及表皮结构、外稃背部具芒与否、芒的伸出位置等性状在种内较为稳定，是本属首要的分类性状。植株疏丛型或密丛型、花序宽大开展或短小紧缩、小穗的大小等性状在分类上具有第二位的重要性。而叶鞘、叶舌、叶片的长宽、颖片边缘是否具睫毛等性状往往在种内没有稳定性，在分类中应该审慎对待。但是，应该特别指出，即便是通常比较稳定可靠的性状， 在少数类群中也可能存在较为复杂的变异，而那些通常没有稳定性的性状，在个别类群中又可能表现出稳定性，在分类上具有重要的价值。 2．叶表皮 在光镜和扫描电镜下观察了叶表皮结构，结果表明：上表皮结构无规律性可循，难以用来分类;下表皮结构为典型的狐茅型，脉间长细胞、刺毛、硅细胞的形态具有一定的分类学意义。 3．外稃表皮 在扫描电镜下观察了外稃表皮结构，结果表明：所有类群的外稃表皮均由长细胞和刺毛组成，偶见硅细胞而无气孔。根据外稃表皮的结构特征可将本属植物分为4类，第1类：长细胞厚壁，边缘显著波状弯曲，刺毛基部浅表型;第2类：长细胞厚壁，边缘微波状或波状弯曲，刺毛基部浅表型;第3类：长细胞薄壁，边缘波状弯曲，刺毛基部下陷;第4类：长细胞厚壁，边缘微波状或波状弯曲，刺毛基部下陷。 4．生态与地理分布 野青茅属植物分布于南北半球的温带地区以及热带的山区，主要生于较潮湿的环境，如林缘、灌丛、低海拔的湿草甸、高山和亚高山草甸、山坡草地等。该属植物在中国主要分布在西南山区和青藏高原，分布种类在海拔3000-4000米最为丰富。 5．区系地理成分分析 中国野青茅属植物的区系地理成分以中国一喜马拉雅成分、中国特有成分为主体，包括环北极成分、旧世界温带成分、中国一日本成分等共5种。认为中国的西南山区至喜马拉雅一带为野青茅属植物的多样性中心之一。 6．根据标本资料，绘制了每一种在中国的地理分布图，以及大部分种的垂直分布柱状图。并首次提供丁8个种的标本绘图。 在．上述工作的基础上，本文对中国野青茅属进行了分类学修订，归并12种，12变种，其中包括新异名16个;作出新组合2个，其中包括1个改级新组合。本文确认了产于中国的该属植物3 1种，3变种（不包括原变种）;另有8种1变种暂存疑。经本文修订后，原中国植物志记载的43种14变种，目前被确认27种2变种。