Short-term exposure to HIV Tat induces glial activation and changes in perineuronal nets.

Despite widespread use of combination antiretroviral therapy (cART), there remains a subset of individuals who display cognitive impairment broadly known as HIV-associated neurocognitive disorder (HAND). Interestingly, HIV-infected cells continuously release the HIV-1 protein Tat even in the presence of cART. Persistent exposure to Tat is proposed to increase both neuroinflammation and neurotoxicity. In vitro evidence shows that matrix metalloproteinases (MMPs) are among the neuroinflammatory molecules induced by Tat, which are known to disrupt specialized neuronal extracellular matrix structures called perineuronal nets (PNNs). PNNs predominantly surround parvalbumin interneurons and help to buffer these cells from oxidant stress and to independently increase their excitability. In order to better understand the link between short-term exposure to Tat, neuroinflammation, and PNNs, we explored the direct effects of Tat on glial cells and neurons. Herein, we report that in mixed glial cultures, Tat directly increases the expression of proinflammatory molecules, including MMP-9. Moreover, direct injection of Tat protein into mouse hippocampus increases the expression of astrocyte and microglia markers as well as MMP-9. The number of PNNs is decreased following Tat exposure, followed later by decreased numbers of hippocampal parvalbumin-expressing neurons. In older mice, Tat induced significant increases in the gene expression of proinflammatory molecules including markers of gliosis, MMPs and complement system proteins. Taken together, these data support a direct effect of Tat on glial-derived MMP expression subsequently affecting PNNs and neuronal health, with older mice more susceptible to Tat-induced inflammation.

Sleep, inflammation, and hemodynamics in rodent models of traumatic brain injury.

Traumatic brain injury (TBI) can induce dysregulation of sleep. Sleep disturbances include hypersomnia and hyposomnia, sleep fragmentation, difficulty falling asleep, and altered electroencephalograms. TBI results in inflammation and altered hemodynamics, such as changes in blood brain barrier permeability and cerebral blood flow. Both inflammation and altered hemodynamics, which are known sleep regulators, contribute to sleep impairments post-TBI. TBIs are heterogenous in cause and biomechanics, which leads to different molecular and symptomatic outcomes. Animal models of TBI have been developed to model the heterogeneity of TBIs observed in the clinic. This review discusses the intricate relationship between sleep, inflammation, and hemodynamics in pre-clinical rodent models of TBI.

Chest CT at X-Ray Dose Using a Noise-Mitigating Weighted Projection: The Thoracic Tomogram. Diagnostic Performance for Pneumonia Detection in Hemato-Oncology Patients.

PURPOSE: To compare the diagnostic performance of a thick-slab reconstruction obtained from an ultra-low-dose CT (termed thoracic tomogram) with standard-of-care low-dose CT (SOC-CT) for rapid interpretation and detection of pneumonia in hemato-oncology patients. METHODS: Hemato-oncology patients with a working diagnosis of pneumonia underwent an SOC-CT followed by an ultra-low-dose CT, from which the thoracic tomogram (TT) was reconstructed. Three radiologists evaluated the TT and SOC-CT in the following categories: (I) infectious/inflammatory opacities, (II) small airways infectious/inflammatory changes, (III) atelectasis, (IV) pleural effusions, and (V) interstitial abnormalities. The TT interpretation time and radiation dose were recorded. Sensitivity, specificity, diagnostic accuracy, ROC, and AUC were calculated with the corresponding power analyses. The agreement between TT and SOC-CT was calculated by Correlation Coefficient for Repeated Measures (CCRM), and the Shrout-Fleiss intra-class correlations test was used to calculate interrater agreement. RESULTS: Forty-seven patients (mean age 58.7 ± 14.9 years; 29 male) were prospectively enrolled. Sensitivity, specificity, accuracy, AUC, and Power for categories I/II/III/IV/V were: 94.9/99/97.9/0.971/100, 78/91.2/86.5/0.906/100, 88.6/100/97.2/0.941/100, 100/99.2/99.3/0.995/100, and 47.6/100/92.2/0.746/87.3. CCRM between TT and SOC-CT for the same categories were .97/.81/.92/.96/.62 with an interobserver agreement of .93/.88/.82/.96/.61. Mean interpretation time was 18.6 ± 5.4 seconds. The average effective radiation dose of TT was similar to a frontal and lateral chest X-ray (0.27 ± 0.08 vs 1.46 ± 0.64 mSv for SOC-CT; P < .01). CONCLUSION: Thoracic tomograms provide comparable diagnostic information to SOC-CT for the detection of pneumonia in immunocompromised patients at one-fifth of the radiation dose with high interobserver agreement.

Harnessing Biomaterials to Study and Direct Antigen-Specific Immunotherapy.

Immunotherapies are an evolving treatment paradigm for addressing cancer, autoimmunity, and infection. While exciting, most of the existing therapies are limited by their specificity─unable to differentiate between healthy and diseased cells at an antigen-specific level. Biomaterials are a powerful tool that enable the development of next-generation immunotherapies due to their tunable synthesis properties. Our lab harnesses biomaterials as tools to study antigen-specific immunity and as technologies to enable new therapeutic vaccines and immunotherapies to combat cancer, autoimmunity, and infections. Our efforts have spanned the study of intrinsic immune profiles of biomaterials, development of novel nanotechnologies assembled entirely from immune cues, manipulation of innate immune signaling, and advanced technologies to direct and control specialized immune niches such as skin and lymph nodes.

Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation.

Antigen-specific tolerance is a key goal of experimental immunotherapies for autoimmune disease and allograft rejection. This outcome could selectively inhibit detrimental inflammatory immune responses without compromising functional protective immunity. A major challenge facing antigen-specific immunotherapies is ineffective control over immune signal targeting and integration, limiting efficacy and causing systemic non-specific suppression. Here we use intra-lymph node injection of diffusion-limited degradable microparticles that encapsulate self-antigens with the immunomodulatory small molecule, rapamycin. We show this strategy potently inhibits disease during pre-clinical type 1 diabetes and allogenic islet transplantation. Antigen and rapamycin are required for maximal efficacy, and tolerance is accompanied by expansion of antigen-specific regulatory T cells in treated and untreated lymph nodes. The antigen-specific tolerance in type 1 diabetes is systemic but avoids non-specific immune suppression. Further, microparticle treatment results in the development of tolerogenic structural microdomains in lymph nodes. Finally, these local structural and functional changes in lymph nodes promote memory markers among antigen-specific regulatory T cells, and tolerance that is durable. This work supports intra-lymph node injection of tolerogenic microparticles as a powerful platform to promote antigen-dependent efficacy in type 1 diabetes and allogenic islet transplantation.

Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps.

Autoimmunity and allergies affect a large number of people across the globe. Current approaches to these diseases target cell types and pathways that drive disease, but these approaches are not cures and cannot differentiate between healthy cells and disease-causing cells. New immunotherapies that induce potent and selective antigen-specific tolerance is a transformative goal of emerging treatments for autoimmunity and serious allergies. These approaches offer the potential of halting-or even reversing-disease, without immunosuppressive side effects. However, translating successful induction of tolerance to patients is unsuccessful. Biomaterials offer strategies to direct and maximize immunological mechanisms of tolerance through unique capabilities such as codelivery of small molecules or signaling molecules, controlling signal density in key immune tissues, and targeting. While a growing body of work in this area demonstrates success in preclinical animal models, these therapies are only recently being evaluated in human trials. This review will highlight the most recent advances in the use of materials to achieve antigen-specific tolerance and provide commentary on the current state of the clinical development of these technologies.

Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination.

Recently approved cancer immunotherapies - including CAR-T cells and cancer vaccination, - show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells ex vivo. Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity. Directly controlling the signals and local environment in LNs could enable potent and safe immunotherapies without cell isolation, engineering, and reinfusion. Here we employ intra-LN (i.LN.) injection of immune signal-loaded biomaterial depots to directly control cancer vaccine deposition, revealing how the combination and geographic distribution of signals in and between LNs impact anti-tumor response. We show in healthy and diseased mice that relative proximity of antigen and adjuvant in LNs - and to tumors - defines unique local and systemic characteristics of innate and adaptive response. These factors ultimately control survival in mouse models of lymphoma and melanoma. Of note, with appropriate geographic signal distributions, a single i.LN. vaccine treatment confers near-complete survival to tumor challenge and re-challenge 100 days later, without additional treatments. These data inform design criteria for immunotherapies that leverage biomaterials for loco-regional LN therapy to generate responses that are systemic and specific, without systemically exposing patients to potent or immunotoxic drugs.

Myosin 5a in the Urinary Bladder: Localization, Splice Variant Expression, and Functional Role in Neurotransmission.

Dysregulation of neurotransmission is a feature of several prevalent lower urinary tract conditions, but the mechanisms regulating neurotransmitter release in the bladder are not completely understood. The unconventional motor protein, Myosin 5a, transports neurotransmitter-containing synaptic vesicles along actin fibers towards the varicosity membrane, tethering them at the active zone prior to reception of a nerve impulse. Our previous studies indicated that Myosin 5a is expressed and functionally relevant in the peripheral nerves of visceral organs such as the stomach and the corpora cavernosa. However, its potential role in bladder neurotransmission has not previously been investigated. The expression of Myosin 5a was examined by quantitative PCR and restriction analyses in bladders from DBA (dilute-brown-nonagouti) mice which express a Myosin 5a splicing defect and in control mice expressing the wild-type Myosin 5a allele. Functional differences in contractile responses to intramural nerve stimulation were examined by ex vivo isometric tension analysis. Data demonstrated Myosin 5a localized in cholinergic nerve fibers in the bladder and identified several Myosin 5a splice variants in the detrusor. Full-length Myosin 5a transcripts were less abundant and the expression of splice variants was altered in DBA bladders compared to control bladders. Moreover, attenuation of neurally-mediated contractile responses in DBA bladders compared to control bladders indicates that Myosin 5a facilitates excitatory neurotransmission in the bladder. Therefore, the array of Myosin 5a splice variants expressed, and the abundance of each, may be critical parameters for efficient synaptic vesicle transport and neurotransmission in the urinary bladder.

Optical properties of dissolved organic matter highlight peatland-like properties in a constructed wetland.

Constructing novel peatland ecosystems can help to restore the long-term carbon accumulating properties of northern soil systems that have been lost through resource extraction. Although mining companies are legally required to restore landscapes following extraction, there are limited tools to evaluate the effectiveness of restoring peat accumulating landscapes. This study analyzed the spatial patterns of the first seven years (n = 575) of dissolved organic matter (DOM) optical characteristics from a pilot watershed built to restore boreal plains peatlands on a former open pit oil sands mine. A principal component analysis (PCA) indicated a very high degree of redundancy in absorption-florescence DOM properties (PARAFAC, HIX, FI, freshness index, SUVA, and peak A, B, C, T, wavelength, and intensity ratios) at this site. The leading principal component indicated a gradient of fresh protein rich inputs, which are highest near the upland region, to older highly degraded DOM, which is highest in the lowland closest to the outlet. Two functionally different reference peatlands, a poor-fen and bog system and a moderate-rich fen, had relatively similar optical DOM characteristics indicating a high level of decomposition at these sites. Over the first seven years, in some regions of the reconstructed lowland the DOM characteristics are becoming increasingly similar to the highly decomposed DOM observed at the reference sites. When combined with carbon flux measurements these findings indicate the potential for long term organic matter accumulation at this reconstructed site.

Biomaterial-enabled induction of pancreatic-specific regulatory T cells through distinct signal transduction pathways.

Autoimmune diseases-where the immune system mistakenly targets self-tissue-remain hindered by non-specific therapies. For example, even molecularly specific monoclonal antibodies fail to distinguish between healthy cells and self-reactive cells. An experimental therapeutic approach involves delivery of self-molecules targeted by autoimmunity, along with immune modulatory signals to produce regulatory T cells (TREG) that selectively stop attack of host tissue. Much has been done to increase the efficiency of signal delivery using biomaterials, including encapsulation in polymer microparticles (MPs) to allow for co-delivery and cargo protection. However, less research has compared particles encapsulating drugs that target different TREG inducing pathways. In this paper, we use poly (lactic-co-glycolide) (PLGA) to co-encapsulate type 1 diabetes (T1D)-relevant antigen and 3 distinct TREG-inducing molecules - rapamycin (Rapa), all-trans retinoic acid (atRA), and butyrate (Buty) - that target the mechanistic target of Rapa (mTOR), the retinoid pathway, and histone deacetylase (HDAC) inhibition, respectively. We show all formulations are effectively taken up by antigen presenting cells (APCs) and that antigen-containing formulations are able to induce proliferation in antigen-specific T cells. Further, atRA and Rapa MP formulations co-loaded with antigen decrease APC activation levels, induce TREG differentiation, and reduce inflammatory cytokines in pancreatic-reactive T cells.

Comparison of conventional chest x ray with a novel projection technique for ultra-low dose CT.

PURPOSE: To compare a novel thick-slab projection technique for ultra-low dose computed tomography (CT; thoracic tomogram) with conventional chest x ray with respect to 13 diagnostic categories. METHODS: With the approval of the institutional ethics board, a dataset was retrospectively collected of 22 consecutive patients who had undergone a clinically requested emergency room conventional chest x ray (CXR) and a same-day standard-of-care non-contrast CT. Scanner specific noise was added to the CT images to simulate a target dose of 0.18 mSv. A novel algorithm was used to post-process CT images as coronal isotropic reformats by applying a voxel-based, locally normalized weighted-intensity projection to generate 2 cm thick slabs with 1 cm overlap. Three chest radiologists with no prior training for the study reviewed the CXR and thoracic tomogram for each case and assessed each diagnostic category (pneumonic infiltrates, pulmonary edema, interstitial lung disease, nodules > 5 mm, nodules < 5 mm, pleural effusion, pericardial effusion, heart size, acute bone fractures, foreign bodies, pneumothorax, mediastinal vessel diameter, free abdominal air) on a Likert scale from -4 (definitely absent/normal) to +4 (definitely present/abnormal). MRMC ROC curves were generated for each category. Time for interpretation and subjective image quality score (0-10) were also assessed. RESULTS: For focal lung disease (pneumonic infiltrates, nodules < 5 mm, nodules > 5mm), the area under the ROC curve (AUC) was significantly higher for thoracic tomograms than CXR (0.803 vs 0.648, respectively, P = 0.02). For non-focal lung disease (pulmonary edema, interstitial lung disease) and effusions (pulmonary, pericardial), the AUC was larger for thoracic tomograms than CXR but the difference did not reach significance (0.870 vs 0.833, P = 0.141; and 0.823 vs 0.752, P = 0.296, respectively). For acute bone fractures and foreign bodies, the AUC was smaller for thoracic tomograms than CXR, the difference was however not significant (0.491 vs 0.532, P = 0.42; and 0.871 vs 0.971, P = 0.39, respectively). Other diagnostic categories had no true positive cases in the dataset. The mean time for interpretation for each was 36.9 and 24.0 s with standard deviations of 0.857 and 5.977. The image quality score for each was 8.2 and 7.8 with standard deviations of 0.970 and 1.614. CONCLUSION: Thoracic tomograms were found to be diagnostically superior to CXR for focal lung disease, at no increased radiation dose. The thoracic tomogram presents an opportunity to improve the standard-of-care for patients who would otherwise receive a conventional CXR.

Energy and carbon fluxes from an oil sands pit lake.

Currently, post-mining landscape plans in the Athabasca Oil Sand Region include large watersheds terminating in pit lakes. In 2012, Base Mine Lake (BML), was constructed with the aim of demonstrating technologies associated with lake reclamation in the region. This paper examines the first 6.5 years of lake-atmosphere energy and carbon exchange. Energetically, BML behaved similar to other northern lakes, storing large quantities of heat in the spring and releasing it in the fall as sensible and latent heat fluxes. At various times a hydrocarbon sheen formed on the lake, which may have suppressed evaporation. However, simple linear relationships failed to statistically quantify the impacts and more comprehensive modelling of the variability may be required. At daily scales, variability in evaporation was well explained by the product of vapour pressure deficit and wind speed as well as the available energy (R2 = 0.74), while sensible heat was explained by the product of wind speed and the difference in air and surface temperature as well as available energy (R2 = 0.85). Spring CH4 fluxes were high, particularly around ice melt, with a maximum flux of 3.3 g m-2 day-1. Otherwise fluxes were low, except during irregular periods. The peak flux of these periods occurred following ~58 h of continuously falling pressure, relating cyclone activity to these large periods of methane emissions. Annually, CO2 and CH4 fluxes were initially high, with median fluxes of 231 mg CO2 m-2 h-1 and 23 mg CH4 m-2 h-1 in 2014. However, the median fluxes reduced quickly and over the least three years of the study (2017 through 2019) the median fluxes declined to 36 mg CO2 m-2 h-1 and 10 mg CH4 m-2 h-1. Overall, BML behaves similar to other boreal lake ecosystems with above average carbon fluxes compared to other constructed reservoirs.

Self-Assembly as a Molecular Strategy to Improve Immunotherapy.

Immunotherapies harness an individual's immune system to battle diseases such as cancer and autoimmunity. During cancer, the immune system often fails to detect and destroy cancerous cells, whereas during autoimmune disease, the immune system mistakenly attacks self-tissue. Immunotherapies can help guide more effective responses in these settings, as evidenced by recent advances with monoclonal antibodies and adoptive cell therapies. However, despite the transformative gains of immunotherapies for patients, many therapies are not curative, work only for a small subset of patients, and lack specificity in distinguishing between healthy and diseased cells, which can cause severe side effects. From this perspective, self-assembled biomaterials are promising technologies that could help address some of the limitations facing immunotherapies. For example, self-assembly allows precision control over the combination and relative concentration of immune cues and directed cargo display densities. These capabilities support selectivity and potency that could decrease off-target effects and enable modular or personalized immunotherapies. The underlying forces driving self-assembly of most systems in aqueous solution result from hydrophobic interactions or charge polarity. In this Account, we highlight how these forces are being used to self-assemble immunotherapies for cancer and autoimmune disease.Hydrophobic interactions can create a range of intricate structures, including peptide nanofibers, nanogels, micelle-like particles, and in vivo assemblies with protein carriers. Certain nanofibers with hydrophobic domains uniquely benefit from the ability to elicit immune responses without additional stimulatory signals. This feature can reduce nonspecific inflammation but may also limit the nanofiber's application because of their inherent stimulatory properties. Micelle-like particles have been developed with the ability to incorporate a range of tumor-specific antigens for immunotherapies in mouse models of cancer. Key observations have revealed that both the total dose of antigen and display density of antigen per particle can impact immune response and efficacy of immunotherapies. These developments are promising benchmarks that could reveal design principles for engineering more specific and personalized immunotherapies.There has also been extensive work to develop platforms using electrostatic interactions to drive assembly of oppositely charged immune signals. These strategies benefit from the ability to tune biophysical interactions between components by altering the ratio of cationic to anionic charge during formulation, or the density of charge. Using a layer-by-layer assembly method, our lab developed hollow capsules composed entirely of immune signals for therapies in cancer and autoimmune disease models. This platform allowed for 100% of the immunotherapy to be composed of immune signals and completely prevents the onset of disease in a mouse model of multiple sclerosis. Layer-by-layer assembly has also been used to coat microneedle patches to target signals to immune cells in the dermal layer. As an alternative to layer-by-layer assembly, one step assembly can be achieved by mixing cationic and anionic components in solution. Additional approaches have created molecular structures that leverage hydrogen bonding for self-assembly. The creativity of engineered self-assembly has led to key insights that could benefit future immunotherapies and revealed aspects that require further study. The challenge now remains to utilize these insights to push development of new immunotherapeutics into clinical settings.

Bistable composite helices with thermal effects.

Morphing technologies use large, seamless changes in the shape of a structure to enable multi-functionality and reconfigurability. Several industrial sectors could benefit from morphing structures, including medical, energy and aerospace which require lightweight, simple and reliable solutions. Composite materials are key to lightweight morphing technologies due to their increased strength- and stiffness-to-mass ratios, stiffness tailorability and excellent fatigue properties, all of which reduce the mass and complexity of these types of structures. By accounting for thermal effects in their analytical description, we enhance the viability of multi-stable composite helical structures. This consideration improves predictions of existing analytical models in comparison with experiments, while also vastly expanding the design space to include antisymmetric and non-symmetric flange lay-up sequences. The developed analytical model is presented and verified using both finite-element models and experiments. By including thermal effects, we show that beneficial new morphing behaviours can be obtained.

Climate-phenology-hydrology interactions in northern high latitudes: Assessing the value of remote sensing data in catchment ecohydrological studies.

We assessed the hydrological implications of climate effects on vegetation phenology in northern environments by fusion of data from remote-sensing and local catchment monitoring. Studies using satellite data have shown earlier and later dates for the start (SOS) and end of growing seasons (EOS), respectively, in the Northern Hemisphere over the last 3 decades. However, estimates of the change greatly depend on the satellite data utilized. Validation with experimental data on climate-vegetation-hydrology interactions requires long-term observations of multiple variables which are rare and usually restricted to small catchments. In this study, we used two NDVI (normalized difference vegetation index) products (at ~25 & 0.5 km spatial resolutions) to infer SOS and EOS for six northern catchments, and then investigated the likely climate impacts on phenology change and consequent effects on catchment water yield, using both assimilated data (GLDAS: global land data assimilation system) and direct catchment observations. The major findings are: (1) The assimilated air temperature compared well with catchment observations (regression slopes and R2 close to 1), whereas underestimations of summer rainstorms resulted in overall underestimations of precipitation (regression slopes of 0.3-0.7, R2 ≥ 0.46). (2) The two NDVI products inferred different vegetation phenology characteristics. (3) Increased mean pre-season temperature significantly influenced the advance of SOS and delay of EOS. The precipitation influence was weaker, but delayed SOS corresponding to increased pre-season precipitation at most sites can be related to later snow melting. (4) Decreased catchment streamflow over the last 15 years could be related to the advance in SOS and extension of growing seasons. Greater streamflow reductions in the cold sites than the warm ones imply stronger climate warming impacts on vegetation and hydrology in colder northerly environments. The methods used in this study have potential for better understanding interactions between vegetation, climate and hydrology in observation-scarce regions.

Using stable isotopes to estimate travel times in a data-sparse Arctic catchment: Challenges and possible solutions.

Use of isotopes to quantify the temporal dynamics of the transformation of precipitation into run-off has revealed fundamental new insights into catchment flow paths and mixing processes that influence biogeochemical transport. However, catchments underlain by permafrost have received little attention in isotope-based studies, despite their global importance in terms of rapid environmental change. These high-latitude regions offer limited access for data collection during critical periods (e.g., early phases of snowmelt). Additionally, spatio-temporal variable freeze-thaw cycles, together with the development of an active layer, have a time variant influence on catchment hydrology. All of these characteristics make the application of traditional transit time estimation approaches challenging. We describe an isotope-based study undertaken to provide a preliminary assessment of travel times at Siksik Creek in the western Canadian Arctic. We adopted a model-data fusion approach to estimate the volumes and isotopic characteristics of snowpack and meltwater. Using samples collected in the spring/summer, we characterize the isotopic composition of summer rainfall, melt from snow, soil water, and stream water. In addition, soil moisture dynamics and the temporal evolution of the active layer profile were monitored. First approximations of transit times were estimated for soil and streamwater compositions using lumped convolution integral models and temporally variable inputs including snowmelt, ice thaw, and summer rainfall. Comparing transit time estimates using a variety of inputs revealed that transit time was best estimated using all available inflows (i.e., snowmelt, soil ice thaw, and rainfall). Early spring transit times were short, dominated by snowmelt and soil ice thaw and limited catchment storage when soils are predominantly frozen. However, significant and increasing mixing with water in the active layer during the summer resulted in more damped steam water variation and longer mean travel times (~1.5 years). The study has also highlighted key data needs to better constrain travel time estimates in permafrost catchments.

Seven temperate terrestrial planets around the nearby ultracool dwarf star TRAPPIST-1.

One aim of modern astronomy is to detect temperate, Earth-like exoplanets that are well suited for atmospheric characterization. Recently, three Earth-sized planets were detected that transit (that is, pass in front of) a star with a mass just eight per cent that of the Sun, located 12 parsecs away. The transiting configuration of these planets, combined with the Jupiter-like size of their host star-named TRAPPIST-1-makes possible in-depth studies of their atmospheric properties with present-day and future astronomical facilities. Here we report the results of a photometric monitoring campaign of that star from the ground and space. Our observations reveal that at least seven planets with sizes and masses similar to those of Earth revolve around TRAPPIST-1. The six inner planets form a near-resonant chain, such that their orbital periods (1.51, 2.42, 4.04, 6.06, 9.1 and 12.35 days) are near-ratios of small integers. This architecture suggests that the planets formed farther from the star and migrated inwards. Moreover, the seven planets have equilibrium temperatures low enough to make possible the presence of liquid water on their surfaces.

Effects of aging upon the host response to implants.

Macrophage polarization during the host response is now a well-accepted predictor of outcomes following material implantation. Immunosenescence, dysregulation of macrophage function, and delayed resolution of immune responses in aged individuals have all been demonstrated, suggesting that host responses to materials in aged individuals should differ from those in younger individuals. However, few studies examining the effects of aging upon the host response have been performed. The present work sought to elucidate the impacts of aging upon the host response to polypropylene mesh implanted into 8-week-old and 18-month-old mice. The results showed that there are significant differences in macrophage surface marker expression, migration, and polarization during the early host macrophage response and delayed resolution of the host response in 18-month-old versus 8-week-old mice. These differences could not be attributed to cell-intrinsic defects alone, suggesting that the host macrophage response to implants is likely also dictated to a significant degree by the local tissue microenvironment. These results raise important questions about the design and testing of materials and devices often intended to treat aged individuals and suggest that an improved understanding of patient- and context-dependent macrophage responses has the potential to improve outcomes in aged individuals. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1281-1292, 2017.

Heat as a groundwater tracer in shallow and deep heterogeneous media: Analytical solution, spreadsheet tool, and field applications.

Groundwater flow advects heat, and thus, the deviation of subsurface temperatures from an expected conduction-dominated regime can be analysed to estimate vertical water fluxes. A number of analytical approaches have been proposed for using heat as a groundwater tracer, and these have typically assumed a homogeneous medium. However, heterogeneous thermal properties are ubiquitous in subsurface environments, both at the scale of geologic strata and at finer scales in streambeds. Herein, we apply the analytical solution of Shan and Bodvarsson (2004), developed for estimating vertical water fluxes in layered systems, in 2 new environments distinct from previous vadose zone applications. The utility of the solution for studying groundwater-surface water exchange is demonstrated using temperature data collected from an upwelling streambed with sediment layers, and a simple sensitivity analysis using these data indicates the solution is relatively robust. Also, a deeper temperature profile recorded in a borehole in South Australia is analysed to estimate deeper water fluxes. The analytical solution is able to match observed thermal gradients, including the change in slope at sediment interfaces. Results indicate that not accounting for layering can yield errors in the magnitude and even direction of the inferred Darcy fluxes. A simple automated spreadsheet tool (Flux-LM) is presented to allow users to input temperature and layer data and solve the inverse problem to estimate groundwater flux rates from shallow (e.g., <1 m) or deep (e.g., up to 100 m) profiles. The solution is not transient, and thus, it should be cautiously applied where diel signals propagate or in deeper zones where multi-decadal surface signals have disturbed subsurface thermal regimes.

Total and methyl mercury concentrations in sediment and water of a constructed wetland in the Athabasca Oil Sands Region.

In the Athabasca Oil Sands Region in northeastern Alberta, Canada, oil sands operators are testing the feasibility of peatland construction on the post-mining landscape. In 2009, Syncrude Canada Ltd. began construction of the 52 ha Sandhill Fen pilot watershed, including a 15 ha, hydrologically managed fen peatland built on sand-capped soft oil sands tailings. An integral component of fen reclamation is post-construction monitoring of water quality, including salinity, fluvial carbon, and priority pollutant elements. In this study, the effects of fen reclamation and elevated sulfate levels on mercury (Hg) fate and transport in the constructed system were assessed. Total mercury (THg) and methylmercury (MeHg) concentrations in the fen sediment were lower than in two nearby natural fens, which may be due to the higher mineral content of the Sandhill Fen peat mix and/or a loss of Hg through evasion during the peat harvesting, stockpiling and placement processes. Porewater MeHg concentrations in the Sandhill Fen typically did not exceed 1.0 ng L(-1). The low MeHg concentrations may be a result of elevated porewater sulfate concentrations (mean 346 mg L(-1)) and an increase in sulphide concentrations with depth in the peat, which are known to suppress MeHg production. Total Hg and MeHg concentrations increased during a controlled mid-summer flooding event where the water table rose above the ground surface in most of the fen. The Hg dynamics during this event showed that hydrologic fluctuations in this system exacerbate the release of THg and MeHg downstream. In addition, the elevated SO4(2-) concentrations in the peat porewaters may become a problem with respect to downstream MeHg production once the fen is hydrologically connected to a larger wetland network that is currently being constructed.