Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody

<p>Abstract</p> <p>Background</p> <p>Selective neutralization of the IL21/IL21R signaling pathway is a promising approach for the treatment of a variety of autoimmune diseases. Ab-01 is a human neutralizing anti-IL21R antibody. In order to ensure that the activities of Ab-01 are restricted to neutralization even under <it>in vitro </it>cross-linking and <it>in vivo </it>conditions, a comprehensive assessment of agonistic potential of Ab-01 was undertaken.</p> <p>Methods</p> <p><it>In vitro </it>antibody cross-linking and cell culture protocols reported for studies with a human agonistic antibody, TGN1412, were followed for Ab-01. rhIL21, the agonist ligand of the targeted receptor, and cross-linked anti-CD28 were used as positive controls for signal transduction. <it>In vivo </it>agonistic potential of Ab-01 was assessed by measuring expression levels of cytokine storm-associated and IL21 pathway genes in blood of cynomolgus monkeys before and after IV administration of Ab-01.</p> <p>Results</p> <p>Using a comprehensive set of assays that detected multiple activation signals in the presence of the positive control agonists, <it>in vitro </it>Ab-01-dependent activation was not detected in either PBMCs or the rhIL21-responsive cell line Daudi. Furthermore, no difference in gene expression levels was detected in blood before and after <it>in vivo </it>Ab-01 dosing of cynomolgus monkeys.</p> <p>Conclusions</p> <p>Despite efforts to intentionally force an agonistic signal from Ab-01, none could be detected.</p

Peer Instruction, Mobile Technology and Learning Effectiveness

The major objective of this study is to have a trial application of Peer Instruction (PI), an innovative pedagogy invented by Eric Mazur in early 1990s, in accounting education. A secondary objective is to test the mobile technology as a medium in applying PI. Involving students in teaching and learning, PI has been proved to be highly successful and widely adopted in various disciplines. Combining UReply as a mobile-enabled platform, we tested the effectiveness of PI. In particular, Intermediate Accounting, a technically challenging accounting course, has been employed as the experiment subject. During September to October, 2017, 6 rounds of PI for 3 topics were carried out. Overall, the resulted 459 valid observations show that, after the peer discussion, (1) the percentage of students hitting the right answer has an average increase of 17.24;(2) students changing from the wrong answer to right answer is more than 3 times of those changing for the opposite direction. Results hold for both qualitative and quantitative questions. The post-test discussion also shows that students reckoned the benefits of PI through UReply. This pilot study demonstrates that PI can also be effectively applied in difficult accounting subjects with modern technology. Echoing the existing literature, however, the success of PI reigns over many factors including culture differences, participants’ motivation, well-designed and tested questions at appropriate complexity and difficulty level

Reactive Sputtering of Bismuth Vanadate Photoanodes for Solar Water Splitting

Bismuth vanadate (BiVO4) has attracted increasing attention as a photoanode for photoelectrochemical (PEC) water splitting. It has a band gap in the visible light range (2.4-2.5 eV) and a valence band position suitable for driving water oxidation under illumination. While a number of methods have been used to make BiVO4 photoanodes, scalable thin film deposition has remained relatively underexplored. Here, we report the synthesis of BiVO4 thin films by reactive sputtering. The use of separate Bi and V sputtering targets allows control of the Bi/V ratio in the film. Under optimized, slightly V-rich conditions, monoclinic phase BiVO4 with photoactivity for water oxidation is obtained. The highest photocurrents, ca. 1 mA cm(-2) at the reversible O-2/H2O potential with simulated AM 1.5G illumination, are obtained with bilayer WO3/BiVO4, where the WO3 serves as a hole-blocking layer

Amorphous Si Thin Film Based Photocathodes with High Photovoltage for Efficient Hydrogen Production

An amorphous Si thin film with TiO2 encapsulation layer is demonstrated as a highly promising and stable photocathode for solar hydrogen production. With platinum as prototypical cocatalyst, a photocurrent onset potential of 0.93 V vs RHE and saturation photocurrent of 11.6 mA/cm(2) are measured. Importantly, the a-Si photocathodes exhibit impressive photocurrent of similar to 6.1 mA/cm(2) at a large positive bias of 0.8 V vs RHE, which is the highest for all reported photocathodes at such positive potential. Ni-Mo alloy is demonstrated as an alternative low-cost catalyst with onset potential and saturation current similar to those obtained with platinum. This low-cost photocathode with high photovoltage and current is a highly promising photocathode for solar hydrogen production

Nonepitaxial Thin-Film InP for Scalable and Efficient Photocathodes

To date, some of the highest performance photocathodes of a photoelectrochemical (PEC) cell have been shown with single-crystalline p-type InP wafers, exhibiting half-cell solar-to-hydrogen conversion efficiencies of over 14%. However, the high cost of single-crystalline InP wafers may present a challenge for future large-scale industrial deployment. Analogous to solar cells, a thin-film approach could address the cost challenges by utilizing the benefits of the InP material while decreasing the use of expensive materials and processes. Here, we demonstrate this approach, using the newly developed thin-film vapor–liquid–solid (TF-VLS) nonepitaxial growth method combined with an atomic-layer deposition protection process to create thin-film InP photocathodes with large grain size and high performance, in the first reported solar device configuration generated by materials grown with this technique. Current–voltage measurements show a photocurrent (29.4 mA/cm²) and onset potential (630 mV) approaching single-crystalline wafers and an overall power conversion efficiency of 11.6%, making TF-VLS InP a promising photocathode for scalable and efficient solar hydrogen generation