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Increasing interest in three-dimensional nanostructures adds impetus toelectron microscopy techniques capable of imaging at or below the nanoscale inthree dimensions. We present a reconstruction algorithm that takes as input afocal series of four-dimensional scanning transmission electron microscopy(4D-STEM) data and transcends the prevalent structure retrieval algorithmassumption of a very thin specimen homogenous along the optic axis. Wedemonstrate this approach by reconstructing the different layers of a leadiridate (Pb$_2$Ir$_2$O$_7$) and yttrium-stabilized zirconia(Y$_{0.095}$Zr$_{0.905}$O$_2$) heterostructure from data acquired with thespecimen in a single plan-view orientation, with the epitaxial layers stackedalong the beam direction.

Increasing interest in three-dimensional nanostructures adds impetus toelectron microscopy techniques capable of imaging at or below the nanoscale inthree dimensions. We present a reconstruction algorithm that takes as input afocal series of four-dimensional scanning transmission electron microscopy(4D-STEM) data. We apply the approach to a lead iridate, Pb$_2$Ir$_2$O$_7$, andyttrium-stabilized zirconia,Y$_{0.095}$Zr$_{0.905}$O$_2$ , heterostructure fromdata acquired with the specimen in a single plan-view orientation, with theepitaxial layers stacked along the beam direction. We demonstrate that Pb-Iratomic columns are visible in the uppermost layers of the reconstructed volume.We compare this approach to the alternative techniques of depth sectioningusing differential phase contrast scanning transmission electron microscopy(DPC-STEM) and multislice ptychographic reconstruction.

Introduction: Informed consent for research biospecimen donations is traditionally obtained through a face-to-face interaction with research staff and by signing an Institutional Review Board (IRB)-approved printed form. Electronic signatures (eSign) are routinely used in the electronic medical record (EMR) for the consenting of clinical services after patients review printed documentation. Our goal was to develop an electronic self-consenting workflow that mimicked clinical services. Specifically, we tested a research consent process for the biobanking of remnant clinical samples that relies solely on clinical resources in a busy outpatient practice. Materials and Methods: The Biorepositories Core Resource (BCR) unit initiated a new enterprise-wide biobanking infrastructure for consenting patients, termed Biospecimen Use for Research-Related Investigations and Translational Objectives (BURRITO). BURRITO is modeled after an established clinical process called Terms and Conditions of Service (TACOS). The TACOS requires patients to annually review printed documentation and self-consent electronically for clinical services. BURRITO also requires patients to review printed documentation and self-consent with eSign to opt-in for remnant biospecimen banking, but patients must complete this process only once. We captured eSign for consents directly into the EMR without research staff. Results: Patients reviewed the IRB-approved documents and self-consented during their cardiology clinic visit. At checkout, their participation preferences were electronically documented by clinic staff. During a 6-month period, 123 patients agreed to donate. After a review of process, a second 3-month period identified 202 patients agreeing to donate. BURRITO did not require face-to-face interactions with research staff, used a "no-paper" eSign for consent, and created discrete fields in the clinical EMR of the patient's preference. Conclusions: BURRITO electronically documents informed consent using an EMR functionality and the least amount of clinical and research resources. Our results show promise for developing institutionally adopted processes, which could leverage existing clinical workflows for universal research consenting and scalability.

COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P. gulae infection in dogs is associated with periodontal disease, which provides a physiologically relevant model to investigate the pharmacology of COR388. In the current study, aged dogs with a natural oral infection of P. gulae and periodontal disease were treated with COR388 by oral administration for up to 90 days to assess lysine-gingipain target engagement and reduction of bacterial load and downstream pathology. In a 28-day dose-response study, COR388 inhibited the lysine-gingipain target and reduced P. gulae load in saliva, buccal cells, and gingival crevicular fluid. The lowest effective dose was continued for 90 days and was efficacious in continuous reduction of bacterial load and downstream periodontal disease pathology. In a separate histology study, dog brain tissue showed evidence of P. gulae DNA and neuronal lysine-gingipain, demonstrating that P. gulae infection is systemic and spreads beyond its oral reservoir, similar to recent observations of P. gingivalis in humans. Together, the pharmacokinetics and pharmacodynamics of COR388 lysine-gingipain inhibition, along with reduction of bacterial load and periodontal disease in naturally occurring P. gulae infection in the dog, support the use of COR388 in targeting lysine-gingipain and eliminating P. gingivalis infection in humans.

In order to evaluate the impact of "The Imagineerium" a 10-week educational project, teachers were asked to observe and rate the behaviour of a pilot sample of 135 participating students both at the beginning and at the end of the 10-week period. Scores recorded on the seven-item Trowsdale Index of Teacher Observation of Student Creativity (TITOSC) showed a significant increase between time one and time two. In order to test the reproducibility of these findings the same index was employed a year later in a replication study among 139 students. On this occasion also, scores recorded on the seven-item Trowsdale Index of Teacher Observation of Student Creativity showed a significant increase between time one and time two. These data support the effectiveness of educational experience in enhancing teacher perception of creativity displayed by individual students.

"The Golden Age of Design may finally be upon us!" or so reported the New York Times in September of 2014. On the one hand everyday personal information appliances emphasized beauty and function. Apple™ took a lead by marketing the "feeling" of the iPod's design. The business world took notice and the cachet of designers soared both in terms of demand and compensation. Regrettably, the "golden age of design" has not swept the Information Systems (IS) discipline along with it. News stories weekly report huge project cost overruns, long delayed delivery dates, and complete project failures with irretrievable sunk costs. What explains the difference? Perhaps IS has not yet embraced the design mindset founded in professions prefixed by: architectural, fashion, industrial, graphic, product, urban, and interior. We examine the mindset of design professionals all but absent in IS education. This mindset fuels the enthusiasm for agile development methodologies. Appropriating it may be a relatively inexpensive re-centering of current IS pedagogy that can pay huge dividends for society down the road as information systems grow more and more essential throughout the commercial and private sectors. We explore this design mindset following Nigel Cross's retrospective on research in "Designerly Ways of Knowing." With that as a frame we name five core elements of that mindset to frame IS pedagogy for design--First Principles of a Designerly Way of Knowing and propose guidelines for situating them in IS education.