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The BA Justice Studies Program (BAJS) was one of the first bachelor’s programs offered at Royal Roads University (RRU). Given the mandate of RRU to provide education for midcareer professionals through a blended learning model, the program was designed to attract professionals working in justice service sectors. Since its inception, the program has lived up to this expectation but has also grown to become a choice for younger students looking to complete a bachelor’s degree. This essay examines the development of the BAJS program within the context of the RRU delivery model. This includes a history of RRU and a discussion of the program within the context of the pedagogy underpinning the RRU Learning and Teaching Model. The design and structure of the BAJS program are identified and the curriculum discussed. This essay concludes with observations on challenges and reflections on future directions for program development.

Disorders of consciousness are neurological conditions characterized by impaired arousal and awareness of self and environment. Behavioural responses are absent or are present but fluctuate. Disorders of consciousness are commonly encountered as a consequence of both acute and chronic brain injuries, yet reliable epidemiological estimates would require inclusive, operational definitions of the concept, as well as wider knowledge dissemination among involved professionals. Whereas several manifestations have been described, including coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state, a comprehensive neurobiological definition for disorders of consciousness is still lacking. The scientific literature is primarily observational, and studies-specific aetiologies lead to disorders of consciousness. Despite advances in these disease-related forms, there remains uncertainty about whether disorders of consciousness are a disease-agnostic unitary entity with a common mechanism, prognosis or treatment response paradigm. Our knowledge of disorders of consciousness has also been hampered by heterogeneity of study designs, variables, and outcomes, leading to results that are not comparable for evidence synthesis. The different backgrounds of professionals caring for patients with disorders of consciousness and the different goals at different stages of care could partly explain this variability. The Prospective Studies working group of the Neurocritical Care Society Curing Coma Campaign was established to create a platform for observational studies and future clinical trials on disorders of consciousness and coma across the continuum of care. In this narrative review, the author panel presents limitations of prior observational clinical research and outlines practical considerations for future investigations. A narrative review format was selected to ensure that the full breadth of study design considerations could be addressed and to facilit

The field of healthcare has increasingly turned its focus towards Large Language Models (LLMs) due to their remarkable performance. However, their performance in actual clinical applications has been underexplored. Traditional evaluations based on question-answering tasks don't fully capture the nuanced contexts. This gap highlights the need for more in-depth and practical assessments of LLMs in real-world healthcare settings. Objective: We sought to evaluate the performance of LLMs in the complex clinical context of adult critical care medicine using systematic and comprehensible analytic methods, including clinician annotation and adjudication. Methods: We investigated the performance of three general LLMs in understanding and processing real-world clinical notes. Concepts from 150 clinical notes were identified by MetaMap and then labeled by 9 clinicians. Each LLM's proficiency was evaluated by identifying the temporality and negation of these concepts using different prompts for an in-depth analysis. Results: GPT-4 showed overall superior performance compared to other LLMs. In contrast, both GPT-3.5 and text-davinci-003 exhibit enhanced performance when the appropriate prompting strategies are employed. The GPT family models have demonstrated considerable efficiency, evidenced by their cost-effectiveness and time-saving capabilities. Conclusion: A comprehensive qualitative performance evaluation framework for LLMs is developed and operationalized. This framework goes beyond singular performance aspects. With expert annotations, this methodology not only validates LLMs' capabilities in processing complex medical data but also establishes a benchmark for future LLM evaluations across specialized domains.

The technique of Soundscripting, the addition of sound cues and sound effects to the canonical pages of any play, is flexible enough to be done at no cost or with all the advantages of modern media. In class, the use of Shakespearean radio dramas or comedies can be effective. The long-term process in class involves four major steps and may take from a few days to a few weeks in and out of class. The steps are: (1) students in collaborative groups read their scenes out loud; (2) they designate and devise the sound effects that fit the text; (3) they render the sound effects alone with a question and answer period by an audience; and (4) they perform the text and sound effects. Key scenes in Shakespeare's "Hamlet" work well for this technique. Some warnings in selecting scenes are: some scenes are too well known and the audience may have a clear inflexible idea of what should be happening; the choices must be judicious because most classes will not have the people or the time to take on many scenes; and teams of students usually need a few roles to play, not a single one. Soundscripting could easily work with any text from any generation as a way to create a fuller effect of interpretation of a script within a classroom. (RS)

Courtroom scenes in literature seem to have a special magic with students (probably because of all the trials seen on television, fiction or non-fiction). Students in a composition and literature course at the University of Nebraska, after reading Thomas Hardy's "Tess of the D'Urbervilles," wrote "closing arguments" for either the prosecution or the defense in the trial that was omitted from the novel. Students were then told to come to class ready to argue either position. They were randomly divided into defense and prosecution teams, collaborated on an opening statement, and presented that statement to the "judge," the instructor. The teams then cross-examined one another. The novel, which so many of them had disliked and found dense, became a nimble tool in their hands. The two sides met again, then gave their final arguments. No decision was given by the "court." Overall, the response to the trial and the assignment was powerfully positive. (RS)

A multidisciplinary care team model, or Heart Team approach, has become a central tenet of cardiovascular care. Though initially applied to the management of heart transplantation and subsequently complex coronary artery disease, the Heart Team is now utilized broadly across cardiovascular medicine, including in the treatment of valvular disease, pulmonary embolism, cardiogenic shock, high-risk pregnancies in patients with pre-existing cardiovascular disease, and adult congenital heart disease. The Heart Team model improves interdisciplinary collaboration among specialties, adherence to societal guidelines, and shared decision-making with patients and families. In this review, we highlight the development and rationale supporting the Heart Team model, address the challenges of implementing a multidisciplinary care team, and discuss the optimal methods to continue to build, optimize, and implement this approach.

Ocular neurodegenerative diseases affecting the retina and the optic nerve have devastating consequences for vision, significantly affecting the quality of life of patients who suffer these pathologies. In the specific case of glaucoma, it is a chronic and complex neurodegeneration process, involving the gradual damage of retinal ganglion cells (RGCs), photoreceptors and other retinal structures, as well as the optic nerve. This process is multifactorial, with a wide range of damage mechanisms such as oxidative stress, inflammation, mitochondrial dysfunction, excitotoxic damage or alteration of gliacells, among others. Increased intraocular pressure (IOP) is the main known modifiable risk factor, although neurodegeneration occurs both in patients with elevated IOP valuesand in subjects with normal IOP values, which is commonly known as normotensive glaucoma. For this reason, neuroprotection is necessary in glaucoma patients with high IOP values as well as normal ones..., Las enfermedades oculares neurodegenerativas que afectan a la retina y al nervio óptico tienen consecuencias perjudiciales para la visión, afectando de manera importante a la calidad de vida de los pacientes que las padecen. En el caso concreto del glaucoma, se trata de un proceso de neurodegeneración crónico y complejo, implicando el daño gradual de las células ganglionares de la retina (RGCs), fotorreceptores y diversas estructuras retinianas, así como del nervio óptico. El proceso de neurodegeneración es multifactorial, con mecanismos de daño muy diversos como estrés oxidativo, inflamación, disfunción mitocondrial, daño excitotóxico o alteración de células de la glía, entre otros. El aumento de la presión intraocular (PIO) es el principal factor de riesgo conocido modificable, aunque la neurodegeneración tiene lugar tanto en pacientes que cursan con valores elevados de la PIO como en sujetos que tienen valores normales dela PIO en lo que se conoce como glaucoma normotensional. Por esta razón, la neurodegeneración debe tratarse tanto en pacientes con valores elevados de la PIO como en normotensionales...

Hydro-pedotransfer functions (PTFs) relate easy-to-measure and readily available soil information to soil hydraulic properties for applications in a wide range of process-based and empirical models, thereby enabling the assessment of soil hydraulic effects on hydrological, biogeochemical, and ecological processes. At least more than four decades of research have been invested to derive such relationships. However, while models, methods, data storage capacity, and computational efficiency have advanced, there are fundamental concerns related to the scope and adequacy of current PTFs, particularly when applied to parameterize models used at the field scale and beyond. Most of the PTF development process has focused on refining and advancing the regression methods, while fundamental aspects have remained largely unconsidered. Most system settings are not captured by existing PTFs, which have been built mostly for agricultural soils in temperate climates. Thus. existing PTFs largely ignorie how parent material, vegetation, land use, and climate affect processes that shape soil hydraulic properties. The PTFs used to parameterise the Richards-Richardson equation are mostly limited to predicting parameters of the van Genuchten-Mualem soil hydraulic functions, despite sufficient evidence demonstrating their shortcomings. Another fundamental issue relates to the diverging scales of derivation and application, whereby PTFs are derived based on laboratory measurements while being often applied at field to regional scales. Scaling, modulation, and constraining strategies exist to alleviate some of these shortcomings in the mismatch between scales. These aspects are addressed here in a joint effort by the members of the International Soil Modelling Consortium (ISMC) Pedotransfer Functions Working Group with the aim to systematise PTF research and provide a roadmap guiding both PTF development and use.

Ca2+ signaling is a regulator of critical cellular processes such as proliferation, metabolism and transcription. In non-excitable cells, intracellular Ca2+ release is mediated by the PLC pathway and the ER resident inositol 1,4,5-trisphosphate (IP3) receptor (IP3R). Upon agonist stimulation, phospholipase C cleaves phosphatidylinositol 4,5-bisphosphate into membrane bound diacylglycerol and soluble IP3, which diffuses and binds IP3Rs causing ER Ca2+ stores to flood into the cytoplasm. Some of this Ca2+ is taken up by mitochondria via the mitochondrial Ca2+ uniporter (MCU) complex where it alters metabolism via regulation of TCA cycle dehydrogenases. More than simple ion channels, IP3Rs are large tetrameric proteins that serve as cellular signaling hubs regulated by a multitude of agonists, antagonists, and modulators. Recently, novel cell models were engineered to stably knockout all three isoforms of IP3Rs(TKO), and despite the biological importance of Ca2+ signaling, these cells display mild phenotypes. The use of TKO cell lines in both structure/function studies related to redox regulation and physiological studies about adaptations to chronic Ca2+ loss was the focus of the current work. Sensitization of IP3R mediated Ca2+ release associated with oxidative stress was thought the be regulated via redox state of IP3R thiols, thus we began by using TKO cells to investigate redox sensitive cysteine residues. Utilizing proteomics and mutagenesis, we identified approximately 20 relevant cysteines, induced mutation of those resides in IP3Rs, and reinserted the mutated receptors back into TKO cells. Ca2+ release assays on oxidant treated mutant and WT receptors revealed a cluster of redox sensitive residues located in the suppressor domain of IP3R1.Pivoting from structure/function studies, TKO cells were then investigated as a model of adaptation to chronic loss of Ca2+ signaling. Biochemical and metabolomic approaches were used to investigate bioenergetic parameters of

Existing literature widely reports on the value of collaborations between mathematicians and mathematics educators, and also how complex those collaborations can be. In this paper, we report on four collaborations that sought to address what mathematics is and who gets to do it. Drawing on the literature and from the careful and intentional work of the collaborators, we offer a framework to capture the richness of those collaborations – one that acknowledges the importance of acknowledging and welcoming the extensive personal and professional experience of each person involved in the collaboration – and a look at how collaborations built with that intentionality and acknowledgment can be impactful for students and institutions and be personally and professionally rewarding for the collaborators.

Some property graph databases do not have a fixed schema, which can result in data type inconsistencies for properties on nodes and relationships, especially when importing data into a running database. Here we present a tool which can rapidly produce a detailed report on every property in the graph. When executed on a large knowledge graph, it allowed us to debug a complex ETL process and enforce 100% data type consistency., Comment: 5 pages, 3 figures, general approach applied to production databases

Engineering matrices for cell therapy requires design criteria that include the ability of these materials to support, protect and enhance cellular behavior in vivo. The chemical and mechanical formulation of the biomaterials can influence not only target cell phenotype but also cellular differentiation. In this study, we have demonstrated the effect of a gelatin (Gtn)—hyaluronic acid (HA) hydrogel on human retinal progenitor cells (hRPCs) and show that by altering the mechanical properties of the materials, cellular behavior is altered as well. We have created an interpenetrating network polymer capable of encapsulating hRPCs. By manipulating the stiffness of the hydrogel, the differentiation potential of the hRPCs was controlled. Interpenetrating network 75 (IPN 75; 75% HA) allowed higher expression of rod photoreceptor markers, whereas cone photoreceptor marker expression was found to be higher in IPN 50. In vivo testing of these living matrices performed in Long–Evans rats showed higher levels of rod photoreceptor marker expression when IPN 75 was injected versus IPN 50. These biomaterials mimic biological cues that are required to simulate the dynamic complexity of natural retinal ECM. These hydrogels can be used as a vehicle for cell delivery in vivo as well as for expansion and differentiation in an in vitro 3D system in a highly reproducible manner.

Soil hydrological processes (SHP) support ecosystems, modulate the impact of climate change on terrestrial systems and control feedback mechanisms between water, energy and biogeochemical cycles. However, land-use changes and extreme events are increasingly impacting these processes. In this Review, we describe SHP across scales and examine their links with soil properties, ecosystem processes and climate. Soil structure influences SHP such as infiltration, soil water redistribution and root water uptake on small scales. On local scales, SHP are driven by root water uptake, vegetation and groundwater dynamics. Regionally, SHP are impacted by extreme events such as droughts, floods, heatwaves and land-use change; however, antecedent and current SHP partially determine the broader effects of extreme events. Emerging technologies such as wireless and automated sensing, soil moisture observation through novel synthetic aperture radars satellites, big data analysis and machine learning approaches offer unique opportunities to advance soil hydrology. These advances, in tandem with the inclusion of more key soil types and properties in models, will be pivotal in predicting the role of SHP during global change.

A synchronized collection of intelligence and investigative capacities, such as would be required to holistically mitigate the emerging threat from unmanned aircraft systems, does not currently exist within the United States government. Furthermore, the entities that do possess the authority, knowledge, and experience to respond are working within largely independent environments. This thesis seeks to identify the best method to collectivize individual agency strengths, unifying intelligence and investigative capacities into one juggernaut-level response against UAS threats. To address this, working groups, task forces, and single agency designation were chosen as potential options specifically for their historical precedence and likelihood of success. Each was compared according to their ability to embrace two defining characteristics: collaboration and commitment. The outcome of the analysis determined that the task force model was ultimately the most effective means to address UAS threats holistically. It mitigates the challenges associated with current technology and legal restrictions by utilizing intelligence and investigative operational capabilities to properly address each of the six steps within the UAS kill chain, all within an environment of high collaboration and commitment. The conclusions and accompanying recommendations outlined in this thesis provide a definitive direction as well as a rational plan of implementation., Civilian, Federal Bureau of Investigation, Approved for public release. Distribution is unlimited.

Misophonia has been characterized as intense negative reactions to specific trigger sounds (often orofacial sounds like chewing, sniffling, or slurping). However, recent research suggests high-level, contextual, and multisensory factors are also involved. We recently demonstrated that neurotypicals negative reactions to aversive sounds (e.g., nails scratching a chalkboard) are attenuated when the sounds are synced with positive attributable video sources (PAVS; e.g., tearing a piece of paper). To assess whether this effect generalizes to misophonic triggers, we developed a Sound-Swapped Video (SSV) database for use in misophonia research. In Study 1, we created a set of 39 video clips depicting common trigger sounds (original video sources, OVS) and a corresponding set of 39 PAVS temporally synchronized with the OVS videos. In Study 2, participants (N = 34) rated the 39 PAVS videos for their audiovisual match and pleasantness. We selected the 20 PAVS videos with best match scores for use in Study 3. In Study 3, a new group of participants (n = 102) observed the 20 selected PAVS and 20 corresponding OVS and judged the pleasantness or unpleasantness of each sound in the two contexts accompanying each video. Afterward, participants completed the Misophonia Questionnaire (MQ). The results of Study 3 show a robust attenuating effect of PAVS videos on the reported unpleasantness of trigger sounds: trigger sounds were rated as significantly less unpleasant when paired with PAVS with than OVS. Moreover, this attenuating effect was present in nearly every participant (99 out of 102) regardless of their score on the MQ. In fact, we found a moderate positive correlation between the PAVS-OVS difference and misophonia severity scores. Overall our results provide validation that the SSV database is a useful stimulus database to study how misophonic responses can be modulated by visual contexts. Here, we release the SSV database with the best 18 PAVS and 18 OVS videos used in Stud

As an essential attribute of organic compounds, polarity has a profound influence on many molecular properties such as solubility and phase transition temperature. Thin layer chromatography (TLC) represents a commonly used technique for polarity measurement. However, current TLC analysis presents several problems, including the need for a large number of attempts to obtain suitable conditions, as well as irreproducibility due to non-standardization. Herein, we describe an automated experiment system for TLC analysis. This system is designed to conduct TLC analysis automatically, facilitating high-throughput experimentation by collecting large experimental data under standardized conditions. Using these datasets, machine learning (ML) methods are employed to construct surrogate models correlating organic compounds' structures and their polarity using retardation factor (Rf). The trained ML models are able to predict the Rf value curve of organic compounds with high accuracy. Furthermore, the constitutive relationship between the compound and its polarity can also be discovered through these modeling methods, and the underlying mechanism is rationalized through adsorption theories. The trained ML models not only reduce the need for empirical optimization currently required for TLC analysis, but also provide general guidelines for the selection of conditions, making TLC an easily accessible tool for the broad scientific community.

Recent advancements in the delivery of therapeutics for retinal diseases include the development of injectable hydrogels, networks of one or more hydrophilic polymers that contain a high-volume fraction of water. These systems are of particular interest due to their biocompatibility, permeability to water-soluble metabolites, and function as minimally invasive injectable delivery vehicles. Recently, hydrogels for ophthalmic applications have been developed that display a controlled release of factors necessary for cellular survival and proliferation. Understanding the relationship between the volume water fraction and the physical, chemical, and diffusion properties of the hydrogel scaffold could aid in the improvement of existing drug delivery treatments for retinal regeneration. In this study, we compared the diffusion and release of human epidermal growth factor (hEGF) encapsulated in different injectable homogenous and heterogenous hydrogels, namely gelatin-hydroxyphenyl propionic acid (Gtn-HPA) and hyaluronic acid-tyramine (HA-Tyr)-based hydrogels. These experimental results were compared with the measured stiffness and water content of these hydrogels and applied to different diffusion theories of polymers to determine the model of best fit. We find that the normalized diffusion and release of hEGF increases with free water content in injectable hydrogels: ranging from 0.176 at 41% free water in HA-Tyr to 0.2 at 53% free water in Gtn-HPA, whereas it decreases with hydrogel stiffness: 600 Pa for Gtn-HPA and 1440 Pa for HA-Tyr. Further, we compared our experimental data with theoretical diffusion models. We found that homogeneous theoretical models, notably the hydrodynamic model (giving a normalized diffusion close to 0.2), provide the most suitable explanation for the measured solute diffusion coefficient. Impact statement Diffusion in a three-dimensional system is a key factor in designing new hydrogel-based materials. It allows to control and predict diffusi

AbstractBiomaterial-based cell replacement approaches to regenerative medicine are emerging as promising treatments for a wide array of profound clinical problems. Here we report an interpenetrating polymer network (IPN) composed of gelatin-hydroxyphenyl propionic acid and hyaluronic acid tyramine that is able to enhance intravitreal retinal cell therapy. By tuning our bioinspired hydrogel to mimic the vitreous chemical composition and mechanical characteristics we were able to improve in vitro and in vivo viability of human retinal ganglion cells (hRGC) incorporated into the IPN. In vivo vitreal injections of cell-bearing IPN in rats showed extensive attachment to the inner limiting membrane of the retina, improving with hydrogels stiffness. Engrafted hRGC displayed signs of regenerating processes along the optic nerve. Of note was the decrease in the immune cell response to hRGC delivered in the gel. The findings compel further translation of the gelatin-hyaluronic acid IPN for intravitreal cell therapy.

We present photometric metallicity measurements for a sample of 2.6 million bulge red clump stars extracted from the Blanco DECam Bulge Survey (BDBS). Similar to previous studies, we find that the bulge exhibits a strong vertical metallicity gradient, and that at least two peaks in the metallicity distribution functions appear at b < -5. We can discern a metal-poor ([Fe/H] ~ -0.3) and metal-rich ([Fe/H] ~ +0.2) abundance distribution that each show clear systematic trends with latitude, and may be best understood by changes in the bulge's star formation/enrichment processes. Both groups exhibit asymmetric tails, and as a result we argue that the proximity of a star to either peak in [Fe/H] space is not necessarily an affirmation of group membership. The metal-poor peak shifts to lower [Fe/H] values at larger distances from the plane while the metal-rich tail truncates. Close to the plane, the metal-rich tail appears broader along the minor axis than in off-axis fields. We also posit that the bulge has two metal-poor populations -- one that belongs to the metal-poor tail of the low latitude and predominantly metal-rich group, and another belonging to the metal-poor group that dominates in the outer bulge. We detect the X-shape structure in fields with |Z| > 0.7 kpc and for stars with [Fe/H] > -0.5. Stars with [Fe/H] < -0.5 may form a spheroidal or "thick bar" distribution while those with [Fe/H] > -0.1 are strongly concentrated near the plane., Comment: 26 pages, 22 figures, accepted for publication in MNRAS; the full data table is very long so only a stub table has been provided here; the full electronic table will be provided through MNRAS upon publication, but early access to the full table will be granted upon request to the authors

The Blanco DECam Bulge Survey (BDBS) has imaged more than 200 square degrees of the southern Galactic bulge, providing photometry in the ugrizy filters for $\sim 250$ million unique stars. The presence of a strong foreground disk population, along with complex reddening and extreme image crowding, has made it difficult to constrain the presence of young and intermediate age stars in the bulge population. We employed an accurate cross-match of BDBS with the latest data release (EDR3) from the Gaia mission, matching more than 140 million sources with BDBS photometry and Gaia EDR3 photometry and astrometry. We relied on Gaia EDR3 astrometry, without any photometric selection, to produce clean BDBS bulge colour-magnitude diagrams (CMDs). Gaia parallaxes were used to filter out bright foreground sources, and a Gaussian mixture model fit to Galactic proper motions could identify stars kinematically consistent with bulge membership. We applied this method to 127 different bulge fields of $1$ deg$^2$ each, with $|\ell| \leq 9.5^\circ$ and $-9.5^\circ \leq b \leq -2.5^\circ$. The astrometric cleaning procedure removes the majority of blue stars in each field, especially near the Galactic plane, where the ratio of blue to red stars is $\lesssim 10\%$, increasing to values $\sim 20\%$ at higher Galactic latitudes. We rule out the presence of a widespread population of stars younger than 2 Gyr. The vast majority of blue stars brighter than the turnoff belong to the foreground population, according to their measured astrometry. We introduce the distance between the observed red giant branch bump and the red clump as a simple age proxy for the dominant population in the field, and we confirm the picture of a predominantly old bulge. Further work is needed to apply the method to estimate ages to fields at higher latitudes, and to model the complex morphology of the Galactic bulge., Comment: 21 pages, 22 figures, accepted for publication in A&A

This curriculum, directed primarily to students in grades five and six, is a 5-week sexuality education program designed to promote sexual abstinence as the best decision young people can make for themselves. The guide is divided into three general areas of emphasis: Knowing Myself, Reltating to Others, and Planning My Future. These sections are divided into six units that focus the content of the curriculum. The lessons in each unit illustrate and reinforce the themes and skills of each unit and section. Section one, "Knowing Myself," helps students feel good about who they are as individuals; presents factual information relating to male and female reproductive anatomy and physiology, and the changes of puberty; and deals with the establishment of values and decision making. The lessons in section two, "Relating to Others," are intended to broaden students' understandings of communication and to develop skills for more effective communication. The final section, "Planning My Future," is designed to help students discover a sense of connection between their decisions and behavior and life outcomes. Teaching tips, suggestions for answering student questions, and a family handout consisting of a permission letter, guidelines for talking to preteens about sex and sexuality, and suggested reading material for parents and guardians are provided. Transparency masters, student handouts and a glossary are included. (LL)

We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs., Ministerio de Economía, Comercio y Empresa (España), Complutense Research Group UCM 920415, Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal), Fundación Jesús Gangoiti Barrera, Instituto de Salud Carlos III, Fundación Multiópticas/Universidad de Navarra, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, TRUE, pub

Arthropod-borne viruses (arboviruses) require replication across a wide range of temperatures to perpetuate. While vertebrate hosts tend to maintain temperatures of approximately 37°C-40°C, arthropods are subject to ambient temperatures which can have a daily fluctuation of > 10°C. Temperatures impact vector competence, extrinsic incubation period, and mosquito survival unimodally, with optimal conditions occurring at some intermediate temperature. In addition, the mean and range of daily temperature fluctuations influence arbovirus perpetuation and vector competence. The impact of temperature on arbovirus genetic diversity during systemic mosquito infection, however, is poorly understood. Therefore, we determined how constant extrinsic incubation temperatures of 25°C, 28°C, 32°C, and 35°C control Zika virus (ZIKV) vector competence and population dynamics within Aedes aegypti and Aedes albopictus mosquitoes. We also examined fluctuating temperatures which better mimic field conditions in the tropics. We found that vector competence varied in a unimodal manner for constant temperatures peaking between 28°C and 32°C for both Aedes species. Transmission peaked at 10 days post-infection for Aedes aegypti and 14 days for Aedes albopictus. Conversely, fluctuating temperature decreased vector competence. Using RNA-seq to characterize ZIKV population structure, we identified that temperature alters the selective environment in unexpected ways. During mosquito infection, constant temperatures more often elicited positive selection whereas fluctuating temperatures led to strong purifying selection in both Aedes species. These findings demonstrate that temperature has multiple impacts on ZIKV biology, including major effects on the selective environment within mosquitoes.

We present a state-of-the-art report on visualization in astrophysics. We survey representative papers from both astrophysics and visualization and provide a taxonomy of existing approaches based on data analysis tasks. The approaches are classified based on five categories: data wrangling, data exploration, feature identification, object reconstruction, as well as education and outreach. Our unique contribution is to combine the diverse viewpoints from both astronomers and visualization experts to identify challenges and opportunities for visualization in astrophysics. The main goal is to provide a reference point to bring modern data analysis and visualization techniques to the rich datasets in astrophysics., Funding Agencies|Carnegie Institution for Science Venture [BPO-700082]; Canadian Institute for Advanced Research Fellowship program; Ahmanson Foundation; NASANational Aeronautics & Space Administration (NASA) [NNX16AB93A]; Swedish e-Science Research Centre; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Swedish Research CouncilSwedish Research CouncilEuropean Commission [DNR:2015-05462]

Red clump (RC) stars are one of the best stellar tracers of the structure of the Milky Way (MW) bulge. Here we report a new view of the double RC through luminosity and color distributions of RC stars in nine bulge fields ($l$ = 0.0$^{\circ}$, $\pm$4.5$^{\circ}$; $b$ = -6.0$^{\circ}$, -7.5$^{\circ}$, -9.0$^{\circ}$) from the Blanco DECam Bulge Survey (BDBS), which covers near-ultraviolet to near-infrared bandpasses. The bright and faint RCs show contrasting distributions in ($u-g$)$_{0}$ and ($u-i$)$_{0}$ colors but similar distributions in ($J-K_{s}$)$_{0}$ with a variation depending on the Galactic longitude, where the bright RC is typically redder than the faint RC. In particular, the RC stars are clearly divided into the bluer and redder populations when using the ($u-g$)$_{0}$ color (($u-g$)$_{0}$ $<$ 2.5 for the bluer RC; ($u-g$)$_{0}$ $\ge$ 2.5 for the redder RC). The bluer stars show a single clump on the faint RC regime, whereas the redder stars form double clumps on both the bright and faint RCs. The bright clump of the redder stars is dominant in the positive longitude fields, while the faint clump of those red stars is significant at negative longitudes. We also confirm that the bluer and redder stars have different peak metallicity through comparison with spectroscopy ($\Delta$[Fe/H] $\sim$ 0.45 dex). Therefore, our results support a scenario whereby the MW bulge is composed of a spheroid of metal-poor stars and a boxy/peanut shape (X-shape) predominantly made up of metal-rich stars., Comment: 15 pages, 17 figures, accepted for publication in A&A

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic loss of cytosolic and/or mitochondrial Ca2+ signaling. Our results show that TKO cells (exhibiting total loss of Ca2+ signaling) are viable, displaying a lower proliferation and oxygen consumption rate, with no significant changes in ATP levels, even when made to rely solely on the TCA cycle for energy production. MCU KO cells also maintained normal ATP levels but showed increased proliferation, oxygen consumption, and metabolism of both glucose and glutamine. However, MCU KO cells were unable to maintain ATP levels and died when relying solely on the TCA cycle for energy. We conclude that constitutive Ca2+ signaling is dispensable for the bioenergetic needs of both IP3R TKO and MCU KO human cancer cells, likely because of adequate basal glycolytic and TCA cycle flux. However, in MCU KO cells, the higher energy expenditure associated with increased proliferation and oxygen consumption makes these cells more prone to bioenergetic failure under conditions of metabolic stress.

Virtual reality headsets, such as the HTC Vive, can be used to model objects, forces, and interactions between objects with high perceived realism and accuracy. Moreover, they can accurately track movements of the head and the hands. This combination makes it possible to provide subjects with precise quantitative feedback on their performance while they are learning a motor task. Juggling is a challenging motor task that requires precise coordination of both hands. Professional jugglers throw objects so that the arc peaks just above head height, and they time their throws so that the second ball is thrown when the first ball reaches its peak. Here, we examined whether it is possible to learn to juggle in virtual reality and whether the height and the timing of the throws can be improved by providing immediate feedback derived from the motion sensors. Almost all participants became better at juggling in the ~30 min session: the height and timing of their throws improved and they dropped fewer balls. Feedback on height, but not timing, improved performance, albeit only temporarily.

A dynamic autonomy allocation framework automatically shifts how much control lies with the human versus the robotics autonomy, for example based on factors such as environmental safety or user preference. To investigate the question of which factors should drive dynamic autonomy allocation, we perform a human subject study to collect ground truth data that shifts between levels of autonomy during shared-control robot operation. Information streams from the human, the interaction between the human and the robot, and the environment are analyzed. Machine learning methods -- both classical and deep learning -- are trained on this data. An analysis of information streams from the human-robot team suggests features which capture the interaction between the human and the robotics autonomy are the most informative in predicting when to shift autonomy levels. Even the addition of data from the environment does little to improve upon this predictive power. The features learned by deep networks, in comparison to the hand-engineered features, prove variable in their ability to represent shift-relevant information. This work demonstrates the classification power of human-only and human-robot interaction information streams for use in the design of shared-control frameworks, and provides insights into the comparative utility of various data streams and methods to extract shift-relevant information from those data., Comment: 7 pages, 4 figures, IROS 2021 Preprint

Cardiac resynchronization therapy (CRT) is an effective treatment for dyssynchronous heart failure. Most patients perform better during clinical tests of cardiac function and may even have their hearts reverse remodel to a more normal state. As many as 30-40% of patients, however, do not respond. A focus of current research is identifying which patients will respond to CRT, though current clinical indications for CRT are based on dyssynchrony and heart failure and not on validated predictors of CRT response. In this thesis, five patient-specific computational models based on non-invasive data were developed and compared with eight previous patient-specific models that were based on more detailed and invasive clinical information to test whether the dyssynchrony metrics from the original study were still predictive in the new group. Model properties such as the volume fraction of negative work (VFNW) and coefficient of variation of work (COVW), that had correlated with patient outcomes in the original cohort, did not correlate with reverse remodeling as measured by reduction in end-systolic volume in the new group. The sensitivity analysis showed that these quantities were sensitive to the parameters of ventricular filling mechanics that could not be included in patient-specific models based on non-invasive data. Non-invasive estimates of filling parameters are available, but their reliability has been questioned. We conclude that it is likely to be necessary to obtain invasive measurements of diastolic pressures for patient-specific models to predict CRT outcomes. However, these measurements are available by cardiac catheterization, which could be justified for CRT patients.

Most soil hydraulic information used in Earth System Models (ESMs) is derived from pedo-transfer functions that use easy-to-measure soil attributes to estimate hydraulic parameters. This parameterization relies heavily on soil texture, but overlooks the critical role of soil structure originated by soil biophysical activity. Soil structure omission is pervasive also in sampling and measurement methods used to train pedotransfer functions. Here we show how systematic inclusion of salient soil structural features of biophysical origin affect local and global hydrologic and climatic responses. Locally, including soil structure in models significantly alters infiltration-runoff partitioning and recharge in wet and vegetated regions. Globally, the coarse spatial resolution of ESMs and their inability to simulate intense and short rainfall events mask effects of soil structure on surface fluxes and climate. Results suggest that although soil structure affects local hydrologic response, its implications on global-scale climate remains elusive in current ESMs.

In this ever-changing world of popular music, we grasp hold of what we enjoy or have delight in. In this document we discuss the highlights of music from the early Jazz era to Hip-hop music in the 21st century. Within general music education we are shifting from the traditional class setting-from where the teacher is imparting knowledge to students to the students teaching students. The classroom instructor is now a facilitator. A new and exciting way for this to happen is through music and popular musics, or music that was deemed popular. Music education-based curricular materials can illustrate the social, political, and economic forces at work in the creation of many of these popular styles. These illustrations are investigated through curricular design, which focuses on the music-making processes of artists/ innovators in these popular styles. In studying the sociocultural meaning behind these styles, student music makers can apply these concepts within their own musics.

This is an exploratory case study of the Tiv of Benue State, Nigeria, and it is primarily focused on identifying the processes, steps, and actors that can facilitate the mainstreaming of Tiv Indigenous peacemaking approaches, as a viable option to the dominant liberal peacebuilding paradigm, for addressing the people’s conflict experiences. I developed and used the Critical Indigenous Qualitative Methodology (CIQPM) to explore this fundamental concern. CIQPM is rooted in the Indigenous research tradition. It is essentially critical, decolonial, and Indigenous. Thus, it challenges every conflict experience perturbing indigenous communities and calls for the revitalization, return and re-insertion of indigenous peacemaking practices and social values to address the experiences. I, therefore, used the following CIQPM methods to collect and analyse data: inquiry conversations, storytelling, yarning, and narratives to collect, analyze and interpret data. I also decolonized and used the Western methods of one-to-one interviews, semi-structured questions and the Creswellian analysis steps, by focusing them toward the re-institutionalization of Tiv indigenous worldviews and peacemaking opportunities. The discoveries made by this study are useful for advancing the ongoing struggle by the Tiv to institutionalize their “Tiv ways” to address their conflict challenges. Also, the study has added interesting insights to existing knowledge and useful knowledge for pedagogy and practice to the field of Peace and Conflict Studies (PACS). The findings are equally beneficial to policymakers and peace-builders who are and will get involved in peace ventures in Tiv land and Africa as a whole. The grounded theory from the study is relevant to the current debate on the legitimacy and viability of African Indigenous peacemaking approaches and the imperative to move from here to the next level, that is, ferreting out ways of mainstreaming the approaches. Finally, as the study that pioneer’s

The Blanco Dark Energy Camera (DECam) Bulge survey is a Vera Rubin Observatory (LSST) pathfinder imaging survey, spanning $\sim 200$ sq. deg. of the Southern Galactic bulge, $-2^\circ <$b$< -13^\circ$ and $-11^\circ <$l$ < +11^\circ$. We have employed the CTIO-4m telescope and the Dark Energy Camera (DECam) to image a contiguous $\sim 200$ sq. deg. region of the relatively less reddened Southern Galactic bulge, in SDSS $u$ + Pan-STARRS$grizy$. Optical photometry with its large colour baseline will be used to investigate the age and metallicity distributions of the major structures of the bulge. Included in the survey footprint are 26 globular clusters imaged in all passbands. Over much of the bulge, we have Gaia DR2 matching astrometry to $i\sim 18$, deep enough to reach the faint end of the red clump. This paper provides the background, scientific case, and description of the survey. We present an array of new reddening-corrected colour-magnitude diagrams that span the extent of Southern Galactic bulge. We argue that a population of massive stars in the blue loop evolutionary phase, proposed to lie in the bulge, are instead at $\sim 2$ kpc from the Sun and likely red clump giants in the old disk. A bright red clump near $(l,b)=(+8^\circ,-4^\circ)$ may be a feature in the foreground disk, or related to the long bar reported in earlier work. We also report the first map of the blue horizontal branch population spanning the BDBS field of regard, and our data does not confirm the reality of a number of proposed globular clusters in the bulge., Comment: 19 pages, 13 figures; MNRAS in press; revision corrects some errors and omissions

The Blanco DECam Bulge Survey (BDBS) imaged more than 200 square degrees of the Southern Galactic bulge using the ugrizY filters of the Dark Energy Camera, and produced point spread function photometry of approximately 250 million unique sources. In this paper, we present details regarding the construction and collation of survey catalogs, and also discuss the adopted calibration and dereddening procedures. Early science results are presented with a particular emphasis on the bulge metallicity distribution function and globular clusters. A key result is the strong correlation (sigma ~ 0.2 dex) between (u-i)o and [Fe/H] for bulge red clump giants. We utilized this relation to find that interior bulge fields may be well described by simple closed box enrichment models, but fields exterior to b ~ -6 degrees seem to require a secondary metal-poor component. Applying scaled versions of the closed box model to the outer bulge fields is shown to significantly reduce the strengths of any additional metal-poor components when compared to Gaussian mixture models. Additional results include: a confirmation that the u-band splits the sub-giant branch in M 22 as a function of metallicity, the detection of possible extra-tidal stars along the orbits of M 22 and FSR 1758, and additional evidence that NGC 6569 may have a small but discrete He spread, as evidenced by red clump luminosity variations in the reddest bands. We do not confirm previous claims that FSR 1758 is part of a larger extended structure., Comment: Accepted for publication in MNRAS; 26 pages

Deep learning (DL) models are being deployed at medical centers to aid radiologists for diagnosis of lung conditions from chest radiographs. Such models are often trained on a large volume of publicly available labeled radiographs. These pre-trained DL models' ability to generalize in clinical settings is poor because of the changes in data distributions between publicly available and privately held radiographs. In chest radiographs, the heterogeneity in distributions arises from the diverse conditions in X-ray equipment and their configurations used for generating the images. In the machine learning community, the challenges posed by the heterogeneity in the data generation source is known as domain shift, which is a mode shift in the generative model. In this work, we introduce a domain-shift detection and removal method to overcome this problem. Our experimental results show the proposed method's effectiveness in deploying a pre-trained DL model for abnormality detection in chest radiographs in a clinical setting.

The high penetration of transportation electrification and its associated charging requirements magnify the interdependency of the transportation and power distribution systems. The emergent interdependency requires that system operators fully understand the status of both systems. To this end, a visualization tool is presented to illustrate the interdependency of battery bus transit and power distribution systems and the associated components. The tool aims at monitoring components from both systems, such as the locations of electric buses, the state of charge of batteries, the price of electricity, voltage, current, and active/reactive power flow. The results showcase the success of the visualization tool in monitoring the bus transit and power distribution components to determine a reliable cost-effective scheme for spatio-temporal charging of electric buses.

Using stem and progenitor cells to treat retinal disorders holds great promise. Using defined culture conditions to maintain the desires phenotype is of utmost clinical importance. We cultured human retinal progenitor cells (hRPCs) in different conditions: such as normoxia (20% oxygen), and hypoxia (5% oxygen) with and without knock-out serum replacement (KOSR) to evaluate its effect on these cells. KOSR is known nutrient supplement often used to replace bovine serum for culturing embryonic or pluripotent stem cells, especially those destined for clinical applications. The purpose of this study was to identify the impact of different environmental and chemical cues to determine if this alters the fate of these cells. Our results indicate that cells cultured with or without KOSR do not show significant differences in viability, but that the oxygen tension can significantly change their viability (higher in hypoxia than normoxia). However, cells with KOSR in hypoxia condition expressed significantly higher stemness markers such as C-myc and Oct4 (31.20% and 13.44% respectively) in comparison to hRPCs cultured in KOSR at normoxia (12.07% and 4.05%). Furthermore, levels of markers for retinal commitment such as rhodopsin were significantly lower in the KOSR supplemented cells in hypoxia culture compared to normoxia. KOSR is known to improve proliferation and maintain stemness of embryonic cells and our experiments suggest that hRPCs maintain their proliferation and stemness characteristics in hypoxia with KOSR supplement. Normoxia, however, results in mature cell marker expression, suggesting a profound effect of oxygen tension on these cells.