Widefield imaging system with two fluorescence and two reflectance channels, a single sCMOS detector, and shielded illumination.

Significance: Widefield microscopy of the entire dorsal part of mouse cerebral cortex enables large-scale ("mesoscopic") imaging of different aspects of neuronal activity with spectrally compatible fluorescent indicators as well as hemodynamics via oxy- and deoxyhemoglobin absorption. Versatile and cost-effective imaging systems are needed for large-scale, color-multiplexed imaging of multiple fluorescent and intrinsic contrasts.

Aim: We aim to develop a system for mesoscopic imaging of two fluorescent and two reflectance channels.

Visual stimulation drives retinotopic acetylcholine release in the mouse visual cortex.

Cholinergic signaling is involved with a variety of brain functions including learning and memory, attention, and behavioral state modulation. The spatiotemporal characteristics of neocortical acetylcholine (ACh) release in response to sensory inputs are poorly understood, but a lack of intra-region topographic organization of cholinergic projections from the basal forebrain has suggested diffuse release patterns and volume transmission. Here, we use mesoscopic imaging of fluorescent ACh sensors to show that visual stimulation results in ACh release patterns that conform to a retinotopic map of visual space in the mouse primary visual cortex, suggesting new modes of functional cholinergic signaling in cortical circuits.

Neurophotonic tools for microscopic measurements and manipulation: status report.

was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, ' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.

A Suite of Neurophotonic Tools to Underpin the Contribution of Internal Brain States in fMRI.

Recent developments in optical microscopy, applicable for large-scale and longitudinal imaging of cortical activity in behaving animals, open unprecedented opportunities to gain a deeper understanding of neurovascular and neurometabolic coupling during different brain states. Future studies will leverage these tools to deliver foundational knowledge about brain state-dependent regulation of cerebral blood flow and metabolism as well as regulation as a function of brain maturation and aging. This knowledge is of critical importance to interpret hemodynamic signals observed with functional magnetic resonance imaging (fMRI).

Additive Manufacturing of Personalized Pharmaceutical Dosage Forms via Stereolithography.

The introduction of three-dimensional printing (3DP) has created exciting possibilities for the fabrication of dosage forms, paving the way for personalized medicine. In this study, oral dosage forms of two drug concentrations, namely 2.50% and 5.

Mass-customization of oral tablets via the combination of 3D printing and injection molding.

The new frontier of medicine is the personalization of treatment to match a patient's individual needs. Fused-filament fabrication (FFF) offers a platform for the personalization of drug dosage forms, but one of its chief shortcomings compared to other tablet production methods such as dry compression and wet granulation is relatively low throughput. Conversely, injection molding (IM) is a manufacturing technique for the high-volume production of parts, but in which individual part customization is both expensive and slow requiring the modification of expensive mold tooling.

Influence of Annealing and Biaxial Expansion on the Properties of Poly(l-Lactic Acid) Medical Tubing.

Poly-l-lactic acid (PLLA) is one of the most common bioabsorbable materials in the medical device field. However, its use in load-bearing applications is limited due to its inferior mechanical properties when compared to many of the competing metal-based permanent and bioabsorbable materials. The objective of this study was to directly compare the influence of both annealing and biaxial expansion processes to improve the material properties of PLLA.

The Influence of Low Shear Microbore Extrusion on the Properties of High Molecular Weight Poly(l-Lactic Acid) for Medical Tubing Applications.

Biodegradable polymers play a crucial role in the medical device field, with a broad range of applications such as suturing, drug delivery, tissue engineering, scaffolding, orthopaedics, and fixation devices. Poly-l-lactic acid (PLLA) is one of the most commonly used and investigated biodegradable polymers. The objective of this study was to determine the influence low shear microbore extrusion exerts on the properties of high molecular weight PLLA for medical tubing applications.

Aging infrastructure creates opportunities for cost-efficient restoration of aquatic ecosystem connectivity.

A hallmark of industrialization is the construction of dams for water management and roads for transportation, leading to fragmentation of aquatic ecosystems. Many nations are striving to address both maintenance backlogs and mitigation of environmental impacts as their infrastructure ages. Here, we test whether accounting for road repair needs could offer opportunities to boost conservation efficiency by piggybacking connectivity restoration projects on infrastructure maintenance.

Minimizing opportunity costs to aquatic connectivity restoration while controlling an invasive species.

Controlling invasive species is critical for conservation but can have unintended consequences for native species and divert resources away from other efforts. This dilemma occurs on a grand scale in the North American Great Lakes, where dams and culverts block tributary access to habitat of desirable fish species and are a lynchpin of long-standing efforts to limit ecological damage inflicted by the invasive, parasitic sea lamprey (Petromyzon marinus). Habitat restoration and sea-lamprey control create conflicting goals for managing aging infrastructure.

Conserving rare species can have high opportunity costs for common species.

Conservation practitioners face difficult choices in apportioning limited resources between rare species (to ensure their existence) and common species (to ensure their abundance and ecosystem contributions). We quantified the opportunity costs of conserving rare species of migratory fishes in the context of removing dams and retrofitting road culverts across 1,883 tributaries of the North American Great Lakes. Our optimization models show that maximizing total habitat gains across species can be very efficient in terms of benefits achieved per dollar spent, but disproportionately benefits common species.

Midwestern US Farmers Perceive Crop Advisers as Conduits of Information on Agricultural Conservation Practices.

Nonpoint source pollution from agricultural land uses continues to pose one of the most significant threats to water quality in the US, with measurable impacts across local, regional, and national scales. The impact and the influence of targeted conservation efforts are directly related to the degree to which farmers are familiar with and trust the entities providing the information and/or outreach. Recent research suggests that farmers consistently rank independent and retail-affiliated crop advisers as among the most trusted and influential sources for agronomic information, but little is understood about whether farmers are willing to receive advice from crop advisers on the use of practices that conserve soil and water, and, if so, whether crop advisers will be perceived as influential.

Designing coastal conservation to deliver ecosystem and human well-being benefits.

Conservation scientists increasingly recognize that incorporating human values into conservation planning increases the chances for success by garnering broader project acceptance. However, methods for defining quantitative targets for the spatial representation of human well-being priorities are less developed. In this study we employ an approach for identifying regionally important human values and establishing specific spatial targets for their representation based on stakeholder outreach.

Understanding the Groundwater Hydrology of a Geographically-Isolated Prairie Fen: Implications for Conservation.

The sources of water and corresponding delivery mechanisms to groundwater-fed fens are not well understood due to the multi-scale geo-morphologic variability of the glacial landscape in which they occur. This lack of understanding limits the ability to effectively conserve these systems and the ecosystem services they provide, including biodiversity and water provisioning. While fens tend to occur in clusters around regional groundwater mounds, Ives Road Fen in southern Michigan is an example of a geographically-isolated fen.

Rating impacts in a multi-stressor world: a quantitative assessment of 50 stressors affecting the Great Lakes.

Ecosystems often experience multiple environmental stressors simultaneously that can differ widely in their pathways and strengths of impact. Differences in the relative impact of environmental stressors can guide restoration and management prioritization, but few studies have empirically assessed a comprehensive suite of stressors acting on a given ecosystem. To fill this gap in the Laurentian Great Lakes, where considerable restoration investments are currently underway, we used expert elicitation via a detailed online survey to develop ratings of the relative impacts of 50 potential stressors.

Enhancing ecosystem restoration efficiency through spatial and temporal coordination.

In many large ecosystems, conservation projects are selected by a diverse set of actors operating independently at spatial scales ranging from local to international. Although small-scale decision making can leverage local expert knowledge, it also may be an inefficient means of achieving large-scale objectives if piecemeal efforts are poorly coordinated. Here, we assess the value of coordinating efforts in both space and time to maximize the restoration of aquatic ecosystem connectivity.

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness.

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes.

Avian use of perennial biomass feedstocks as post-breeding and migratory stopover habitat.

Increased production of biomass crops in North America will require new agricultural land, intensify the cultivation of land already under production and introduce new types of biomass crops. Assessing the potential biodiversity impacts of novel agricultural systems is fundamental to the maintenance of biodiversity in agricultural landscapes, yet the consequences of expanded biomass production remain unclear. We evaluate the ability of two candidate second generation biomass feedstocks (switchgrass, Panicum virgatum, and mixed-grass prairie) not currently managed as crops to act as post-breeding and fall migratory stopover habitat for birds.

West Nile virus impacts in American crow populations are associated with human land use and climate.

West Nile virus (WNV) was first detected in the western hemisphere during the summer of 1999, reawakening US public awareness of the potential severity of vector-borne pathogens. Since its New World introduction, WNV has caused disease in human, avian, and mammalian communities across the continent. American crows () are a highly susceptible WNV host and when modeled appropriately, changes in crow abundances can serve as a proxy for the spatio-temporal presence of WNV.

Lidar remote sensing variables predict breeding habitat of a Neotropical migrant bird.

A topic of recurring interest in ecological research is the degree to which vegetation structure influences the distribution and abundance of species. Here we test the applicability of remote sensing, particularly novel use of waveform lidar measurements, for quantifying the habitat heterogeneity of a contiguous northern hardwoods forest in the northeastern United States. We apply these results to predict the breeding habitat quality, an indicator of reproductive output of a well-studied Neotropical migrant songbird, the Black-throated Blue Warbler (Dendroica caerulescens).

Terrestrial reserve networks do not adequately represent aquatic ecosystems.

Protected areas are a cornerstone of conservation and have been designed largely around terrestrial features. Freshwater species and ecosystems are highly imperiled, but the effectiveness of existing protected areas in representing freshwater features is poorly known. Using the inland waters of Michigan as a test case, we quantified the coverage of four key freshwater features (wetlands, riparian zones, groundwater recharge, rare species) within conservation lands and compared these with representation of terrestrial features.

Risk of hypogonadism from scatter radiation during pelvic radiation in male patients with rectal cancer.

Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer.

Methods And Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.

Spatial scaling of avian population dynamics: population abundance, growth rate, and variability.

Synchrony in population fluctuations has been identified as an important component of population dynamics. In a previous study, we determined that local-scale (<15-km) spatial synchrony of bird populations in New England was correlated with synchronous fluctuations in lepidopteran larvae abundance and with the North Atlantic Oscillation. Here we address five questions that extend the scope of our earlier study using North American Breeding Bird Survey data.

Native osteoprotegerin gene transfer inhibits the development of murine osteolytic bone disease induced by tumor xenografts.

Objective: Multiple myeloma is a plasma cell malignancy characterized by the development of osteolytic lesions leading to bone pain, pathologic fractures, and hypercalcemia. Osteoprotegerin (OPG) is a potent inhibitor of osteoclast differentiation and activation, but is limited as a therapeutic agent due to its short circulating half-life. In order to overcome these limitations, the therapeutic effects of native OPG gene transfer are examined.