The Rise of Retinal Organoids for Vision Research

Retinal degenerative diseases lead to irreversible blindness. Decades of research into the cellular and molecular mechanisms of retinal diseases, using either animal models or human cell-derived 2D systems, facilitated the development of several therapeutic interventions. Recently, human stem cell-derived 3D retinal organoids have been developed. These self-organizing 3D organ systems have shown to recapitulate the in vivo human retinogenesis resulting in morphological and functionally similar retinal cell types in vitro. In less than a decade, retinal organoids have assisted in modeling several retinal diseases that were rather difficult to mimic in rodent models. Retinal organoids are also considered as a photoreceptor source for cell transplantation therapies to counteract blindness. Here, we highlight the development and field’s improvements of retinal organoids and discuss their application aspects as human disease models, pharmaceutical testbeds, and cell sources for transplantations.     

Taking on a wider view: public value interests of construction clients in a changing construction industry

For financial and strategic reasons, public and semi-public construction clients increasingly depend on private parties to carry out public service delivery. They subcontract operational responsibilities to private parties while remaining socio-politically responsible for ensuring public values. Public administration literature mainly addresses the importance of procedural and performance values in safeguarding public values. However, safeguarding the quality of the built environment also requires a focus on product values. In this study, we aim to increase the understanding of the meaning and significance of public values in the daily practice of public construction clients and identify the challenges they face in commissioning these seemingly opposing values. A set of semi-structured interviews with the public administrators of a variety of public and semi-public construction client organizations in the Netherlands shows that both internal and external factors influence the collaborative practices between clients and contractors. This causes a value shift from an emphasis on procedural values to managing performance and product values, indicating that clients need to take on a wider view on public values. Six main public value dilemmas were found that complicate the task of developing an open, transparent and sustainable long-term client–contractor relationship. The current contractual system, however, lacks the flexibility to facilitate this product-based value view in construction.     

Design methodology for barrier‐based two phase flow distributor

The barrier‐based distributor is a multiphase flow distributor for a multichannel microreactor which assures flow uniformity and prevents channeling between the two phases. For N number of reaction channels, the barrier‐based distributor consists of a gas manifold, a liquid manifold, N barrier channels for the gas, N barrier channels for the liquid, and N mixers for mixing the phases before the reaction channels. The flow distribution is studied numerically using a method based on the hydraulic resistive networks (RN). The single phase hydraulic RN model (Commenge et al., 2002;48:345–358) is extended for two phases gas‐liquid Taylor flow. For Re_GL <30, the accuracy for the model was above 90%. The developed‐model was used to study the effects of fabrication tolerance and barrier channel dimensions. A design methodology has been proposed as an algorithm to determine the required hydraulic resistance in the barrier channels and their dimensions. This methodology is demonstrated using a numerical example. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

Manufacturing of integrative membrane carriers by novel powder injection molding

Although offering distinctive economic benefits the mass fabrication of carrier devices incorporating membranes as quasi-monolithic devices reveals strong technological challenges. Powder injection molding would be an effective process for this purpose, however, manufacturing parts of considerable wall thickness variations and to meet strong precision demands remains problematic. To evaluate novel ways of process conducts as well as to determine influencing parameters a demonstrator design had been developed which enabled the generation of thin membranes by controlled piston movement. Suitable lay-out of the runner system had been determined with the help of simulation calculations. The combined injection + embossing process conduct enabled to reduce minimum membrane thickness to about a half. Investigation of parameter influence showed that embossing force and gap width before injection have an ameliorative effect on membrane quality whereas the embossing delay time had no significant impact.     

Characterization of a miniaturized liquid bridge for nL sample infusion: a comparative study of sample flush-out behavior using flow simulations and direct ESI-MS analysis

In this work we shed light on the microfluidics of a miniaturized liquid bridge that forms the central part of a so-called “capillary gap sampler,” a novel device for rapid and seamless injection of nanoliter sample volumes into an electrospray ionization mass spectrometer (ESI-MS). Parameters relevant for sample flush-out at the liquid bridge and in the spray capillary were identified by systematic variation of the capillary dimensions, the linear buffer flow rate (2.1–34 mm/s) and molecular weight of the analytes (0.5–30 kDa). We found that a reduction in capillary wall thickness by a factor of 1.6 significantly influences analyte peak shapes, leads to an inversion of the relationship between peak width and analyte molecular weight, and allows a fivefold decrease in peak width for large molecules down to 5 s. The results could be verified and explained by simulations, in which the presence of diffusion-controlled “dead zones” at the liquid bridge and dispersion in the spray tip that depend on analyte molecular weight were identified as key factors relevant for the sample flush-out process. The merging of simulations and experimental data gives useful hints toward the re-design of a spray tip as built-in ESI-MS interface for an optimized gap sampler performance.     

Stevia – Ein natürliches Sü?ungsmittel mit gesundheitlichem Zusatznutzen?

Eine Besonderheit der natürlichen Sü?stoffe aus Stevia rebaudiana soll ihre vorteilhafte pharmakologische Wirkung sein. In der wissenschaftlichen Literatur wird immer wieder ein Einfluss auf den menschlichen Blutzuckergehalt und den Blutdruck genannt. Dies w?re ein Novum: Ein Sü?ungsmittel mit Heilwirkung.     

Der Verdacht der Simulation

The Suspicion of Simulation. A Psychiatric Case History between Appropriation and Disciplinary Action at the End of the 19th Century. This case history explores how the question of agency was dealt with historically in two developing, normative orders of deviant behaviour. Examining the institutional career of the supposed adulterer, marriage swindler, and craft baker, we can trace the different observation regimes and systems of knowledge acquisition in the prison and in psychiatry. In both institutions there was talk of simulated madness; the explanations, however, were different. For the prison doctors and civil servants, the baker was a criminal; his deviant behaviour was a matter of consciously planned-out deception. For the examining psychiatrist, on the other hand, he was mentally ill and could not be held responsible for his own behaviour.