Design of protease-resistant myelin basic protein-derived peptides by cleavage site directed amino acid substitutions

Multiple Sclerosis (MS) is considered to be a T cell-mediated autoimmune disease. An attractive strategy to prevent activation of autoaggressive T cells in MS, is the use of altered peptide ligands (APL), which bind to major histocompatibility complex class II (MHC II) molecules. To be of clinical use, APL must be capable of resisting hostile environments including the proteolytic machinery of antigen presenting cells (APC). The current design of APL relies on cost- and labour-intensive strategies. To overcome these major drawbacks, we used a deductive approach which involved modifying proteolytic cleavage sites in APL. Cleavage site-directed amino acid substitution of the autoantigen myelin basic protein (MBP) resulted in lysosomal protease-resistant, high-affinity binding peptides. In addition, these peptides mitigated T cell activation in a similar fashion as conventional APL. The strategy outlined allows the development of protease-resistant APL and provides a universal design strategy to improve peptide-based immunotherapeutics

The importance of post marketing quality control

BACKGROUND A previously published study reported on the nonlinear behaviour for airway pressure and tidal volume of the adjustable pressure-limiting (APL) valve of the Aisys CS2 anaesthesia machine (GE Healthcare, Madison, Wisconsin, USA) during manual bag ventilation. In co-operation with the manufacturer, an adapted APL valve was developed. OBJECTIVE To test and characterise the performance of an adapted APL valve and assess its clinical usability. DESIGN Two-stage study, consisting of an in-vitro testing of an adapted APL valve in a baby and adolescent lung model, followed by a clinical experience survey of anaesthesia personnel after the official implementation of the new APL valve into clinical routine. SETTING Anaesthesia Department at the University Children's Hospital Zurich. MAIN OUTCOME MEASURES Airway pressures and inspiratory tidal volumes during opening and closure of the APL valve at different settings. Likert scale assessment of performance expectance, effort expectance, behavioural intention and safety of the APL valve during clinical use. RESULTS In contrast to the original APL valve of the GE Aisys CS2, the adapted APL valve showed a nearly linear increase in airway pressures as well as in the tidal volumes measured. Most importantly, the measured pressures never exceeded the set pressures. Based on the experimental findings, all original APL valves of the GE Aisys CS2 were replaced by the adapted APL valve. Two months later, an anonymised and standardised questionnaire was handed out to all employees working with the adapted APL valve. Analysis of the questionnaire indicated that the adapted APL valve is easier and more precise to handle in the daily routine than the original one. CONCLUSION The newly adapted APL valve for the GE Aisys CS2 has considerably improved its linearity at lower pressures and supports our institution's bag mask ventilation practices

Adapted Primary Literature (APL): An Effective Authentic Text Option for the Science Classroom

The intention of this literature review is to advocate for the incorporation of Adapted Primary Literature (APL) into secondary science classroom instruction in order to aid such science curriculum in achieving balanced authenticity. APL is a valuable instructional text option due to its novel design, an optimal compromise between authenticity and accessibility. APL is a superior reflection of authentic science as it is for professionals of science and in representation of the nature of science (NOS) than Secondary Literature (SL) and textbooks, the dominating scientific text genres of most secondary science classroom instruction. Yet, APL is more accessible in text sophistication and structure than arguably the most authentic genre, Primary Scientific Literature (PSL). In other words, due to such negotiated design, APL could prove invaluable at addressing a multitude of science education objectives associated with authenticity, such as those pertaining to the following common categorical headings: literacy, argumentation, inquiry, concept competence, and the nature of science, to name a few. In addition, APL may address the contemporary science education goals of increased student interest, motivation, and pursuit of scientific endeavors. After all, the current and likely future direction of the global economy, professional atmosphere, consumer decision-making, technological advancements, and environmental threats has required that science education be concerned with far more than just student memorization of content within an isolated, singular disciplinary year. Suggested remedies for potential incorporation challenges, areas in need of further research, and common contrary research positions will be included to provide a comprehensive and supportive examination of APL implementation. No instructive technique is without tradeoffs. Like any other educative method, the success of APL implementation is greatly influenced by the quality of surrounding instruction. Possessing scientific authenticity “in some defined way is never sufficient justification by itself for engaging in an educational practice. Authenticity is no guarantee of effectiveness” (Norris et al., 2009, p. 407)

Technological aids to the efficient assessment of prior earning

Joosten-ten Brinke, D., Van der Klink, M., Kicken, W., & Sloep, P. B. (2011). Technological aids to the efficient Assessment of Prior Learning. In G. Magoulas (Ed.), E-Infrastructures and technologies for lifelong learning: Next generation environments (pp. 316-336). Hershey: IGI Global.It is generally acknowledged that learning and education plays a prominent part throughout employees’ careers across their entire lifespan. In our era of lifelong learning Assessment of Prior Learning (APL) is a powerful means for enhancing employees’ further professional development and learning, formally and informally. Though there is a growing attention for APL, the procedures, design, development and maintenance of APL remain a quite costly and time-consuming experience. After a description of the background and features of APL, this chapter examines the possibilities for re-using and interoperability by means of e-technologies. The chapter discusses the major components of the APL procedure, including the current possibilities for exchange and operability (e.g. specifications of QTI, IMS). The chapter concludes with a description and validation of an educational model of assessment for APL

Hybrid waveguide-bulk multi-path interferometer with switchable amplitude and phase

We design and realise a hybrid interferometer consisting of three paths based on integrated as well as on bulk optical components. This hybrid construction offers a good compromise between stability and footprint on one side and means of intervention on the other. As experimentally verified by the absence of higher-order interferences, amplitude and phase can be manipulated in all paths independently. In conjunction with single photons, the setup can, therefore, be applied for fundamental investigations on quantum mechanics.Comment: accepted in APL Photonic

Design and Development of Advanced Adaptive Polymer Lenses

The dissertation presented here describes advancements made in adaptive polymer lens design and implementation. Singlets and doublets lenses were constructed for visible, short- wavelength infrared (SWIR), and middle-wavelength infrared (MWIR)applications. The lenses are implemented in a variety of tactical imaging systems to demonstrate their performance. A process was developed that defines the allowable fabrication variables, first for APL singlets and then for APL doublets. A first-order finite element model is described that enables going from an optical design to APL fabrication. This model was then extended to the design of fluidic doublets, which are equivalent to their two-element glass counter-parts. Two constant volume fluidic chambers were enclosed by three flexible membranes resulting in a variable focal length doublet. Chromatic focal shift was then used to compare numerical modeling to experimentally measured results. These same tools, methodology, and process were lastly used in the definition and fabrication of the SWIR and MWIR adaptive polymer lens for tactical systems. vi Imaging and illumination systems are presented, based on these lensesnotably an adaptive zoom imaging system, in the MWIR. This is the first known instance of such a system in this band