Teaching Physical Science Through Technology: Middle School VCU PHY 591

Teaching Physical Science through Technology is a new 3-credit laboratory-and-lecture based course designed to serve as an introduction to the teaching of physical science concepts at the middle school level. Physical science phenomena are presented through investigations of commonly known applications of technology and focus on the Virginia Science Standards of Learning for 6th Grade Science and the Physical Science courses. Topics include matter, gravity, mechanics, heat, optics, electricity and magnetism, and computers as seen in their roles in common devices. The development of the course includes assessment from six semesters, collaboration with other institutions including the Science Museum of Virginia, and an 800 page text written by Adam Niculescu

Psychiatric blood biomarkers: avoiding jumping to premature negative or positive conclusions

Blood biomarkers may provide a scientifically useful and clinically usable peripheral signal in psychiatry, as they have been doing for other fields of medicine. Jumping to premature conclusions, negative or positive, can create confusion in this field. Reproducibility is a hallmark of good science. We discuss some recent examples from this dynamic field, and show some new data in support of previously published biomarkers for suicidality (SAT1, MARCKS and SKA2). Methodological clarity and rigor in terms of biomarker discovery, validation and testing is needed. We propose a set of principles for what constitutes a good biomarker, similar in spirit to the Koch postulates used at the birth of the field of infectious diseases

Precision medicine for suicidality: from universality to subtypes and personalization

Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a ‘liquid biopsy’ approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator

Optimal Consumer Network Structure Formation under Network Effects: Seeds Controllability and Visibility

Understanding the process of software adoption is of paramount importance to software start-ups. We study a monopolistic seller’s optimal consumer network structure formation (seeding, segmentation, sequencing, and pricing strategies) under network effects. We demonstrate the importance of adoption sequencing as well as controllability over the seeding process to seller’s profit, consumer surplus, and social welfare. Under multi-pricing, full information, and full control over the seeding process, with both multiplicative and additive forms of network effects, we show that all segments contain only paying customers except the first one, which contains both seeded and paying customers; and segments are opened in order of the customer valuation. Further, the seller’s optimal strategy is socially optimal. Under single-pricing and limited seeding control, worst case seeding (where all seeds go to the high-valuation customers) leads to higher social welfare and consumer surplus than uniform seeding, as the former covers a larger portion of the market while charging a lower price. In the case of random seeding with limited control, we identify an optimal strategy and conditions under which the optimal price is not affected by the randomness of seeding

Probing the structure of Nucleons in Electromagbetic Interactions

Open problems in the study of the nucleon structure using electromagnetic probes are discussed. The focus is on experimental aspects in the regime of strong interaction QCD. Significant progress in our understanding of the nucleon structure in this domain of QCD may be expected in the first decade of the next millenium. This is due to major experimental and theoretical efforts currently underway in this field.Comment: 9 pages, 6 figures, plenary talk at PANIC9

Towards precision medicine for pain: diagnostic biomarkers and repurposed drugs

We endeavored to identify objective blood biomarkers for pain, a subjective sensation with a biological basis, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We studied psychiatric patients, a high risk group for co-morbid pain disorders and increased perception of pain. For discovery, we used a powerful within-subject longitudinal design. We were successful in identifying blood gene expression biomarkers that were predictive of pain state, and of future emergency department (ED) visits for pain, more so when personalized by gender and diagnosis. MFAP3, which had no prior evidence in the literature for involvement in pain, had the most robust empirical evidence from our discovery and validation steps, and was a strong predictor for pain in the independent cohorts, particularly in females and males with PTSD. Other biomarkers with best overall convergent functional evidence for involvement in pain were GNG7, CNTN1, LY9, CCDC144B, and GBP1. Some of the individual biomarkers identified are targets of existing drugs. Moreover, the biomarker gene expression signatures were used for bioinformatic drug repurposing analyses, yielding leads for possible new drug candidates such as SC-560 (an NSAID), and amoxapine (an antidepressant), as well as natural compounds such as pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), and apigenin (a plant flavonoid). Our work may help mitigate the diagnostic and treatment dilemmas that have contributed to the current opioid epidemic

Localizability of Wireless Sensor Networks: Beyond Wheel Extension

A network is called localizable if the positions of all the nodes of the network can be computed uniquely. If a network is localizable and embedded in plane with generic configuration, the positions of the nodes may be computed uniquely in finite time. Therefore, identifying localizable networks is an important function. If the complete information about the network is available at a single place, localizability can be tested in polynomial time. In a distributed environment, networks with trilateration orderings (popular in real applications) and wheel extensions (a specific class of localizable networks) embedded in plane can be identified by existing techniques. We propose a distributed technique which efficiently identifies a larger class of localizable networks. This class covers both trilateration and wheel extensions. In reality, exact distance is almost impossible or costly. The proposed algorithm based only on connectivity information. It requires no distance information

Fly, Wake-up, Find: UAV-based Energy-efficient Localization for Distributed Sensor Nodes

A challenging application scenario in the field of industrial Unmanned Aerial Vehicles (UAVs) is the capability of a robot to find and query smart sensor nodes deployed at arbitrary locations in the mission area. This work explores the combination of different communication technologies, namely, Ultra-Wideband (UWB) and Wake-Up Radio (WUR), with a UAV that acts as a "ubiquitous local-host"of a Wireless Sensor Network (WSN). First, the UAV performs the localization of the sensor node via multiple UWB range measurements, and then it flies in its proximity to perform energy-efficient data acquisition. We propose an energy-efficient and accurate localization algorithm - based on multi-lateration - that is computationally inexpensive and robust to in-field noise. Aiming at minimizing the sensor node energy consumption, we also present a communication protocol that leverages WUR technology to minimize ON-time of the power-hungry UWB transceiver on the sensors. In-field experimental evaluation demonstrates that our approach achieves a sub-meter localization precision of the sensor nodes - i.e., down to 0.6 m - using only three range measurements, and runs in 4 ms on a low power microcontroller (ARM Cortex-M4F). Due to the presence of the WUR and the proposed lightweight algorithm, the entire localization-acquisition cycle requires only 31 mJ on the sensor node. The approach is suitable for several emerging Industrial Internet of Things application scenarios where a mobile vehicle needs to estimate the location of static objects without any precise knowledge of their position

Significance of solutions of the inverse Biot-Savart problem in thick superconductors

The evaluation of current distributions in thick superconductors from field profiles near the sample surface is investigated theoretically. A simple model of a cylindrical sample, in which only circular currents are flowing, reduces the inversion to a linear least squares problem, which is analyzed by singular value decomposition. Without additional assumptions about the current distribution (e.g. constant current over the sample thickness), the condition of the problem is very bad, leading to unrealistic results. However, any additional assumption strongly influences the solution and thus renders the solutions again questionable. These difficulties are unfortunately inherent to the inverse Biot-Savart problem in thick superconductors and cannot be avoided by any models or algorithms