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Macros can abort the process by setting the Abort to true in the context dictionary. Scripting engine is only initialized if macro files are present. TempFolder registry setting added for control of temporary folder for the printer port.

Malay language was added. New runonce command line parameter for gui.

Fix: The RunOnError command line is now executed if a macro raises an error. Fix of error when output format is different from PDF and encryption was enabled.

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Fix of problem with the Save As dialog. Fix for reading Unicode postscript properties written using octal numbers on Windows Fix for missing text on buttons on Windows Fix for selecting the correct file extension when using the Save As dialog. Problem where the installer reported "Not implemented" has been fixed. Xmp' on 64 bit systems.

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Support for Ghostscript 8. New feature: Create linearized PDF files for optimized web viewing. New feature: Show list of page thumb nail images when opening the PDF.

Fixed Thai translation. Allows appending with the same file name as the output even if the append file doesn't exist.

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EXE parameter names are no longer case sensitive. Tutorial reviews should provide an introduction and overview of an important topic of relevance to the journal readership. The topic should be of relevance to both researchers who are new to the field as well as experts and provide a good introduction to the development of a subject, its current state and indications of future directions the field is expected to take.

Tutorial reviews should not contain unpublished original research. Perspectives present an authoritative state-of-the-art account of a research field.

A Perspective may take the form of a personal account of research, or a critical analysis of a topic of current interest. In either form, some new unpublished research may be included.

Medium throughput breathing human primary cell alveolus-on-chip model | Scientific Reports

Journal specific guidelines The following guidelines are journal specific. Contributions should be explained concisely. All authors should have agreed to their individual contributions ahead of submission and these should accurately reflect contributions to the work.

Please note that for any manuscript with more than 10 co-authors the corresponding author must provide the editor with a statement to specify the contribution of each author.

The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB.

Introduction The human blood-brain barrier BBB is a unique and selective physiological barrier that controls transport between the blood and the central nervous system CNS to maintain homeostasis for optimal brain function.

The brain microvascular endothelium differs from that found in peripheral capillaries based on its complex tight junctions, which restrict paracellular transit and instead, require that transcytosis be used to transport molecules from the blood through the endothelium and into the CNS 2. BMVECs also express multiple broad-spectrum efflux pumps on their luminal surface that inhibit uptake of lipophilic molecules, including many drugs, into the brain 3 , 4.

The astrocytes and pericytes provide signals that are required for differentiation of the BMVECs 5 , 6 , and all three cell types are needed to maintain BBB integrity in vivo as well as in vitro 7 , 8. The BBB is also of major clinical relevance because dysfunction of the BBB is observed in many neurological diseases, and the efficacy of drugs designed to treat neurological disorders is often limited by their inability to cross the BBB 9.

Unfortunately, neither animal models of the BBB nor in vitro cultures of primary or immortalized human BMVECs alone effectively mimic the barrier and transporter functions of the BBB observed in humans 10 , 11 , Thus, there is a great need for a human BBB model that could be used to develop new and more effective CNS-targeting therapeutics and delivery technologies as well as advance fundamental and translational research 7 , 8.

Development of human induced pluripotent stem iPS cell technology has enabled differentiation of brain-like microvascular endothelial cells iPS-BMVECs that exhibit many properties of the human BBB, including well-organized tight junctions, expression of nutrient transporters and polarized efflux transporter activity 13 , Here, we describe the development of an enhanced human BBB model created with microfluidic Organ Chip culture technology 19 that contains human iPS-BMVECs interfaced with primary human pericytes and astrocytes, and that uses a developmentally inspired differentiation protocol 20 , 21 , The resulting human BBB Chip exhibits physiologically relevant levels of human BBB function for at least 1 week in vitro, including low barrier permeability and expression of multiple efflux pumps and transporter functions that are required for analysis of drug and therapeutic antibody transport.

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