14 research outputs found
Organs-on-chips: into the next decade
Organs-on-chips (OoCs) could be useful at various stages of drug discovery and development, providing insight regarding human organ physiology in both normal and disease contexts, as well as accurately predicting developmental drug safety and efficacy. This Review discusses the advances that have enabled OoCs to demonstrate physiological relevance, and the challenges and opportunities that need to be tackled to tap the full potential of OoC utility for translational research.Organs-on-chips (OoCs), also known as microphysiological systems or 'tissue chips' (the terms are synonymous), have attracted substantial interest in recent years owing to their potential to be informative at multiple stages of the drug discovery and development process. These innovative devices could provide insights into normal human organ function and disease pathophysiology, as well as more accurately predict the safety and efficacy of investigational drugs in humans. Therefore, they are likely to become useful additions to traditional preclinical cell culture methods and in vivo animal studies in the near term, and in some cases replacements for them in the longer term. In the past decade, the OoC field has seen dramatic advances in the sophistication of biology and engineering, in the demonstration of physiological relevance and in the range of applications. These advances have also revealed new challenges and opportunities, and expertise from multiple biomedical and engineering fields will be needed to fully realize the promise of OoCs for fundamental and translational applications. This Review provides a snapshot of this fast-evolving technology, discusses current applications and caveats for their implementation, and offers suggestions for directions in the next decade
How to move ionized gas: an introduction to the dynamics of HII regions
This review covers the dynamic processes that are important in the evolution
and structure of galactic HII regions, concentrating on an elementary
presentation of the physical concepts and recent numerical simulations of HII
region evolution in a non-uniform medium.
The contents are as follows:
(1) The equations (Euler equations; Radiative transfer; Rate equations; How
to avoid the dynamics; How to avoid the atomic physics).
(2) Physical concepts (Static photoionization equilibrium; Ionization front
propagation; Structure of a D-type front; Photoablation flows; Other
ingredients - Stellar winds, Radiation pressure, Magnetic fields,
Instabilities).
(3) HII region evolution (Early phases: hypercompact and ultracompact
regions; Later phases: compact and extended regions; Clumps and turbulence).Comment: To be published as a chapter in 'Diffuse Matter from Star Forming
Regions to Active Galaxies' - A volume Honouring John Dyson. Eds. T. W.
Harquist, J. M. Pittard and S. A. E. G. Falle. 25 pages, 7 figures. Some
figures degraded to meet size restriction. Full-resolution version available
at http://www.ifront.org/wiki/Dyson_Festschrift_Chapte
Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development
The first microfluidic microphysiological systems (MPS) entered the academic scene more than 15 years ago and were considered an enabling technology to human (patho)biology in vitro and, therefore, provide alternative approaches to laboratory animals in pharmaceutical drug development and academic research. Nowadays, the field generates more than a thousand scientific publications per year. Despite the MPS hype in academia and by platform providers, which says this technology is about to reshape the entire in vitro culture landscape in basic and applied research, MPS approaches have neither been widely adopted by the pharmaceutical industry yet nor reached regulated drug authorization processes at all. Here, 46 leading experts from all stakeholders - academia, MPS supplier industry, pharmaceutical and consumer products industries, and leading regulatory agencies - worldwide have analyzed existing challenges and hurdles along the MPS-based assay life cycle in a second workshop of this kind in June 2019. They identified that the level of qualification of MPS-based assays for a given context of use and a communication gap between stakeholders are the major challenges for industrial adoption by end-users. Finally, a regulatory acceptance dilemma exists against that background. This t4 report elaborates on these findings in detail and summarizes solutions how to overcome the roadblocks. It provides recommendations and a roadmap towards regulatory accepted MPS-based models and assays for patients' benefit and further laboratory animal reduction in drug development. Finally, experts highlighted the potential of MPS-based human disease models to feedback into laboratory animal replacement in basic life science research.Toxicolog
Engineering multicellular living systems-A Keystone Symposia report
The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium "Organoids as Tools for Fundamental Discovery and Translation"
Engineering multicellular living systems-A Keystone Symposia report
The ability to engineer complex multicellular systems has enormous potential to inform our understanding of biological processes and disease and alter the drug development process. Engineering living systems to emulate natural processes or to incorporate new functions relies on a detailed understanding of the biochemical, mechanical, and other cues between cells and between cells and their environment that result in the coordinated action of multicellular systems. On April 3-6, 2022, experts in the field met at the Keystone symposium "Engineering Multicellular Living Systems" to discuss recent advances in understanding how cells cooperate within a multicellular system, as well as recent efforts to engineer systems like organ-on-a-chip models, biological robots, and organoids. Given the similarities and common themes, this meeting was held in conjunction with the symposium "Organoids as Tools for Fundamental Discovery and Translation".Stem cells & developmental biolog
Region-specific microdissection library and single-copy microclones for human chromosome 2p11–p13
Down syndrome: characterisation of a case with partial trisomy of chromosome 21 owing to a paternal balanced translocation (15;21) (q26;q22.1) by FISH.
ICRF/Edge Interaction Guidelines for ICRF Antenna Design and Initial ICRF/Edge Interaction Experiments on the Tore Supra Tokamak
Phylogenetic relationships among Brazilian howler monkeys, genus Alouatta (Platyrrhini, Atelidae), based on <FONT FACE=Symbol>g</FONT>1-globin pseudogene sequences
The genus Alouatta (howler monkeys) is the most widely distributed of New World primates, and has been arranged in three species groups: the Central American Alouatta palliata group and the South American Alouatta seniculus and Alouatta caraya groups. While the latter is monotypic, the A. seniculus group encompasses at least three species (A. seniculus, A. belzebul and A. fusca). In the present study, approximately 600 base pairs of the g1-globin pseudogene were sequenced in the four Brazilian species (A. seniculus, A. belzebul, A. fusca and A. caraya). Maximum parsimony and maximum likelihood methods yielded phylogenetic trees with the same arrangement: {A. caraya [A. seniculus (A. fusca, A. belzebul)]}. The most parsimonious tree had bootstrap values greater than 82% for all groupings, and strength of grouping values of at least 2, supporting the sister clade of A. fusca and A. belzebul. The study also confirmed the presence of a 150-base pair Alu insertion element and a 1.8-kb deletion in the g1-globin pseudogene in A. fusca, features found previously in the remaining three species. The cladistic classification based on molecular data agrees with those of morphological studies, with the monospecific A. caraya group being clearly differentiated from the A. seniculus group.<br>Os guaribas, do gĂŞnero Alouatta, que sĂŁo os primatas do Novo Mundo com maior distribuição geográfica, tĂŞm sido colocados em trĂŞs grupos de espĂ©cies: o grupo Alouatta palliata da AmĂ©rica central, e os grupos sulamericanos Alouatta seniculus e Alouatta caraya. Este Ăşltimo Ă© monotĂpico, mas o grupo A. seniculus inclui pelo menos trĂŞs espĂ©cies (A. seniculus, A. belzebul e A. fusca). Neste estudo, foram seqĂĽenciados aproximadamente 600 pares de base do pseudogene globina g1 nas quatro espĂ©cies brasileiras (A. seniculus, A. belzebul, A. fusca e A. caraya). Os mĂ©todos de máxima parcimĂ´nia e máxima verossimilhança produziram árvores filogenĂ©ticas com o mesmo arranjo: {A. caraya [A. seniculus (A. fusca, A. belzebul)]}. A árvore mais parcimoniosa apresentou valores de bootstrap maiores de 82% para todos os agrupamentos, e valores de força de ligação de pelo menos 2, apoiando o agrupamento irmĂŁo de A. fusca e A. belzebul. O estudo tambĂ©m confirmou a presença em A. fusca do elemento de inserção Alu, com 150 pares de base, e uma deleção de 1,8 kb no pseudogene globina g1 já conhecidos nas demais espĂ©cies de guaribas. A classificação cladĂstica baseada em dados moleculares Ă© congruente com as de estudos morfolĂłgicos, com um isolamento claro do grupo monoespecĂfico A. caraya em relação ao grupo A. seniculus