281 research outputs found
Virtus vs. Virtue: The Role of Honor in Shakespeare’s Coriolanus
An analysis of Shakespeare\u27s Coriolanus with an emphasis on the juxtaposition of the concepts of English Christian and Roman honor
Winning at the Graduate Level of Warfare: Six Core Factors of a Successful Counterinsurgency Campaign and the Example of Sierra Leone
The most common form of warfare so far in the 21st Century has been insurgencies and counterinsurgencies, types of warfare which are particularly challenging for industrialized Western nations to wage effectively. This paper identifies six factors of primary importance which form the key to a successful counterinsurgency campaign. These factors are legitimacy, clarity, beneficial geopolitical factors, restraint, intellectual understanding, and an enduring commitment. This paper argues that these factors must all be present for a counterinsurgency campaign to succeed, and argues that without these factors being accounted for a counterinsurgency will fail. The British humanitarian intervention in Sierra Leone in 2000 and their subsequent counterinsurgency campaign is here considered as a type case study to illustrate the importance of these factors in waging a successful counterinsurgency campaign
Editor\u27s Note
Editor\u27s introduction to Volume 4, Issue 1 of The Catalyst
A universal method for automated gene mapping
Small insertions or deletions (InDels) constitute a ubiquituous class of sequence polymorphisms found in eukaryotic genomes. Here, we present an automated high-throughput genotyping method that relies on the detection of fragment-length polymorphisms (FLPs) caused by InDels. The protocol utilizes standard sequencers and genotyping software. We have established genome-wide FLP maps for both Caenorhabditis elegans and Drosophila melanogaster that facilitate genetic mapping with a minimum of manual input and at comparatively low cost
Evaluation of 3D hepatic tissue models for bioprinting
Introduction: Drug-induced liver injury is the leading cause of acute liver failure and post-market drug withdrawals. In vivo animal studies cannot be totally translated to humans; therefore, there’s huge demand of novel in vitro human models. 3D culture conditions would increase models longevity while bioprinting technology is expected to improve their functionality by the in vivo-like cell spatial patterning.
Aim: The present project aims at the establishment and characterization of printed liver tissue-like models as co-culture of human cells such as hepatocytes, stellate and endothelial cells in order to reproduce a functional liver sinusoid.
3D equivalents were printed to assess hepatic cells printability (printing test), while high-density hepatocytes models were manually produced and characterized in order to simulate in-vivo cellular density conditions and define experimental parameters for bioprinting process.
Materials and methods:
- Printing test: HepG2 cells were mixed 6*106 cells/ml with bioink, PEG-based ink produced in house. Matrigel solution was added to further improve cell viability during the printing process. Cell mixture was printed by direct dispensing in a spiral pattern and polymerized at 365nm wavelength. Models were analysed up to 7 days for cell proliferation, viability and morphology.
- High-density 3D models: High-density HepG2 discs and drop models were manually produced mixing 2:1 HepG2 “paste” with ink (supplemented with matrigel). Models were polymerized by exposure to 365nm wavelength for few seconds and cultivated up to 28 days. The equivalents were analysed for cell viability and albumin secretion as well as processed for histological analyses (cell proliferation, tissue-like intercellular tight junctions and lipid storage investigation).
Results and discussion:
- Bioprinting as well as ink is suitable for HepG2 viability and proliferation up to 7 days (15.84 ± 1.46 fold change increase day 7 vs day1). Printed HepG2 are homogenously distributed and round-shaped, forming agglomerates that increase in size over time.
- HepG2-ink-matrigel equivalents are long-term stable characterized by high and constant cell viability up to 28 days. The models resemble native liver with respect to the high cell density and due to the ink supplementation can easily be printed into tissue-like models with exact cell patterning and defined structure. Models are currently under investigation for tissue functionality and morphology and will be subsequently printed.
Conclusions: Bioprinting shows high potential for the manufacture of high-density liver tissue-like models. The printing of different cell types (hepatocytes, stellate and endothelial cells) will allow producing organotypical 3D liver equivalents
ZHAW Waedenswil : a new approach in the fight against cancer
A happy coincidence brought Dr Markus Rimann from ZHAW Wädenswil together with Dr Andreas Meyer from the start-up FGen and PD Dr Emanuela Felley-Bosco, Molecular Oncologist at Zurich University Hospital, to develop a technology platform for the manufacture and high throughput analysis of single mesothelioma spheroids. Armin Picenoni, former student in Chemistry for the Life Sciences at ZHAW, confirmed everything in writing his Master Thesis on this Innosuisse project
Design and in vivo characterization of self-inactivating human and non-human lentiviral expression vectors engineered for streptogramin-adjustable transgene expression
Adjustable transgene expression is considered key for next-generation molecular interventions in gene therapy scenarios, therapeutic reprogramming of clinical cell phenotypes for tissue engineering and sophisticated gene-function analyses in the post-genomic era. We have designed a portfolio of latest generation self-inactivating human (HIV-derived) and non-human (EIAV-based) lentiviral expression vectors engineered for streptogramin-adjustable expression of reporter (AmySΔS, EYFP, SAMY, SEAP), differentiation-modulating (human C/EBP-α) and therapeutic (human VEGF) transgenes in a variety of rodent (CHO-K1, C2C12) and human cell lines (HT-1080, K-562), human and mouse primary cells (NHDF, PBMC, CD4+) as well as chicken embryos. Lentiviral design concepts include (i) binary systems harboring constitutive streptogramin-dependent transactivator (PIT) and PIT-responsive transgene expression units on separate lentivectors; (ii) streptogramin-responsive promoters (PPIR8) placed 5′ of desired transgenes; (iii) within modified enhancer-free 3′-long terminal repeats; and (iv) bidirectional autoregulated configurations providing streptogramin-responsive transgene expression in a lentiviral one-vector format. Rigorous quantitative analysis revealed HIV-based direct PPIR-transgene configurations to provide optimal regulation performance for (i) adjustable expression of intracellular and secreted product proteins, (ii) regulated differential differentiation of muscle precursor cell lines into adipocytes or osteoblasts and (iii) conditional vascularization fine-tuning in chicken embryos. Similar performance could be achieved by engineering streptogramin-responsive transgene expression into an autoregulated one-vector format. Powerful transduction systems equipped with adjustable transcription modulation options are expected to greatly advance sophisticated molecular interventions in clinically and/or biotechnologically relevant primary cells and cell line
Advances in the biofabrication of 3D skin in vitro : healthy and pathological models
The relevance for in vitro three-dimensional (3D) tissue culture of skin has been present for almost a century. From using skin biopsies in organ culture, to vascularized organotypic full-thickness reconstructed human skin equivalents, in vitro tissue regeneration of 3D skin has reached a golden era. However, the reconstruction of 3D skin still has room to grow and develop. The need for reproducible methodology, physiological structures and tissue architecture, and perfusable vasculature are only recently becoming a reality, though the addition of more complex structures such as glands and tactile corpuscles require advanced technologies. In this review, we will discuss the current methodology for biofabrication of 3D skin models and highlight the advantages and disadvantages of the existing systems as well as emphasize how new techniques can aid in the production of a truly physiologically relevant skin construct for preclinical innovation
Standardized 3D bioprinting of soft tissue models with human primary cells
Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application
In vitro characterization of a new composite material for biomedical applications and 3D (bio)printing
Study goal: The present project aims at evaluating the cytocompatibility and printability of a new composite material, based on a mixture of a new methacrylate-based monomer developed within a CTI project (18514.1 PFLS-LS) and glass-ceramic powder supplemented with co- and photo-initiators (patent in preparation).
This study is the basis to demonstrate the suitability of the biomaterial, for biomedical applications, such as stent, orthopedic implants and hearing aid components, as well as for 3D (bio)printing
Key findings:
- Cultivation, proliferation and differentiation of three different human cell types were successfully established on composite material discs (1cm diameter, 1mm height). Biological activity was shown
- The material is suitable for 3D (bio)printing, printing protocols were established
- The new composite material is suitable for cell and tissue interaction in biomedical application
- …