Rapid Prototyping Assisted Design and Development of Inter-Vertebral Implants

This paper presents a case study of applying rapid prototyping in assisting in the design and development of inter-vertebral implants for spine fusions. The major process of design and implant development, its biological and mechanical requirements, the approach for developing a 3D reconstructive vertebral anatomy model, the inter-vertebral implant CAD model, and the integration with a finite element analysis for the implant's structural analysis are presented. The process of 3D Printing of the vertebral anatomy and the inter-vertebral implant is described. The application of the prototyping model in assisting in the inter-vertebral anatomic fitting, in guiding the implant's geometric design, in helping with the virtual surgical planning, and in understanding the implant's mechanical properties and structural stability are discussed.Mechanical Engineerin

An ACE2 Microbody Containing a Single Immunoglobulin Fc Domain Is a Potent Inhibitor of SARS-CoV-2

Soluble forms of angiotensin-converting enzyme 2 (ACE2) have recently been shown to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We report on an improved soluble ACE2, termed a “microbody,” in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin (Ig) heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibits entry of SARS-CoV-2 spike protein pseudotyped virus and replication of live SARS-CoV-2 in vitro and in a mouse model. Its potency is 10-fold higher than soluble ACE2, and it can act after virus bound to the cell. The microbody inhibits the entry of β coronaviruses and virus with the variant D614G spike. The ACE2 microbody may be a valuable therapeutic for coronavirus disease 2019 (COVID-19) that is active against viral variants and future coronaviruses

Dissecting Driver Behaviors Under Cognitive, Emotional, Sensorimotor, and Mixed Stressors

In a simulation experiment we studied the effects of cognitive, emotional, sensorimotor, and mixed stressors on driver arousal and performance with respect to (wrt) baseline. In a sample of n = 59 drivers, balanced in terms of age and gender, we found that all stressors incurred significant increases in mean sympathetic arousal accompanied by significant increases in mean absolute steering. The latter, translated to significantly larger range of lane departures only in the case of sensorimotor and mixed stressors, indicating more dangerous driving wrt baseline. In the case of cognitive or emotional stressors, often a smaller range of lane departures was observed, indicating safer driving wrt baseline. This paradox suggests an effective coping mechanism at work, which compensates erroneous reactions precipitated by cognitive or emotional conflict. This mechanisms’ grip slips, however, when the feedback loop is intermittently severed by sensorimotor distractions. Interestingly, mixed stressors did not affect crash rates in startling events, suggesting that the coping mechanism’s compensation time scale is above the range of neurophysiological latency

Connecting Past with Present: A Mixed-Methods Science Ethics Course and its Evaluation

We present a graduate science ethics course that connects cases from the historical record to present realities and practices in the areas of social responsibility, authorship, and human/animal experimentation. This content is delivered with mixed methods, including films, debates, blogging, and practicum; even the instructional team is mixed, including a historian of science and a research scientist. What really unites all of the course's components is the experiential aspect: from acting in historical debates to participating in the current scientific enterprise. The course aims to change the students' culture into one deeply devoted to the science ethics cause. To measure the sought after cultural change, we developed and validated a relevant questionnaire. Results of this questionnaire from students who took the course, demonstrate that the course had the intended effect on them. Furthermore, results of this questionnaire from controls indicate the need for cultural change in that cohort. All these quantitative results are reinforced by qualitative outcomes

Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants

Delineating the operational envelope of mobile and conventional EDA sensing on key body locations

Electrodermal activity (EDA) is an important affective indicator, measured conventionally on the fingers with desktop sensing instruments. Recently, a new generation of wearable, battery-powered EDA devices came into being, encouraging the migration of EDA sensing to other body locations. To investigate the implications of such sensor/location shifts in psychophysiological studies we performed a validation experiment. In this experiment we used startle stimuli to instantaneously arouse the sympathetic system of n = 23 subjects while sitting. Startle stimuli are standard but minimal stressors, and thus ideal for determining the sensor and location resolution limit. The experiment revealed that precise measurement of small EDA responses on the fingers and palm is feasible either with conventional or mobile EDA sensors. By contrast, precise measurement of small EDA responses on the sole is challenging, while on the wrist even detection of such responses is problematic for both EDA modalities. Given that affective wristbands have emerged as the dominant form of EDA sensing, researchers should beware of these limitations

Evaluating smartphone-based user interface designs for a 2D psychological questionnaire

This study explored various user interface designs to transition a two dimensional (2D) questionnaire from its paper-and-pencil testing format to the mobile platform. The current administration of the test limits its usage beyond the lab environment. Creating a mobile version would facilitate ubiquitous administration of the test. Yet, the mobile design must be at least as good as its paper-based counterpart in terms of input accuracy and user interaction efforts. We developed four user interface designs, each of which featured a specific interaction approach. These approaches included displaying the 2D space of the questionnaire in its original form (M1), inputting one variable at a time on the 2D space (M2), dissolving the 2D space into two one-dimensional ordinal scales (M3), and orienting the input selections to the diagonal axes (M4). The designs were tested by a total of 34 participants, aged 18 to 52 years. The study results find the first three interaction approaches (M1-M3) effective but the fourth approach inefficient. Furthermore, the results indicate that the two-tap designs (M2 and M3) are equally as good as the one-tap design (M1)

Dissecting Driver Behaviors under Cognitive, Emotional, Sensorimotor, and Mixed Stressors

In a simulation experiment we studied the effects of cognitive, emotional, sensorimotor, and mixed stressors on driver arousal and performance with respect to (wrt) baseline. In a sample of n = 59 drivers, balanced in terms of age and gender, we found that all stressors incurred significant increases in mean sympathetic arousal accompanied by significant increases in mean absolute steering. The latter, translated to significantly larger range of lane departures only in the case of sensorimotor and mixed stressors, indicating more dangerous driving wrt baseline. In the case of cognitive or emotional stressors, often a smaller range of lane departures was observed, indicating safer driving wrt baseline. This paradox suggests an effective coping mechanism at work, which compensates erroneous reactions precipitated by cognitive or emotional conflict. This mechanisms' grip slips, however, when the feedback loop is intermittently severed by sensorimotor distractions. Interestingly, mixed stressors did not affect crash rates in startling events, suggesting that the coping mechanism's compensation time scale is above the range of neurophysiological latency