Contemporary (2001) and ‘Little Ice Age’ glacier extents in the Buordakh Massif, Cherskiy Range, north east Siberia

The Buordakh Massif of the Cherskiy Range of sub-arctic north east Siberia, Russia has a cold continental climate and supports over 80 glaciers. Despite previous research in the region, a georeferenced map of the glaciers has only recently been completed and an enhanced version of it is reproduced in colour here. The mountains of this region reach heights in excess of 3,000 m and the glaciers on their slopes range in size from 0.1 to 10.4 km2. The mapping has been compiled through the interpretation of Landsat 7 ETM+ satellite imagery from August 2001 which has been augmented by data from a field campaign undertaken at the same time. The glaciers of the region are of the cold, ‘firn-less’ continental type and their mass balance relies heavily on the formation of superimposed ice. Moraines which lie in front of the glaciers by up to a few kilometres are believed to date from the Little Ice Age (ca. 1550-1850 AD). Over half of the glaciers mapped have shown marked retreat from these moraines

In situ characterization of CD4+ T cell behavior in mucosal and systemic lymphoid tissues during the induction of oral priming and tolerance

The behavior of antigen-specific CD4+ T lymphocytes during initial exposure to antigen probably influences their decision to become primed or tolerized, but this has not been examined directly in vivo. We have therefore tracked such cells in real time, in situ during the induction of oral priming versus oral tolerance. There were marked contrasts with respect to rate and type of movement and clustering between naive T cells and those exposed to antigen in immunogenic or tolerogenic forms. However, the major difference when comparing tolerized and primed T cells was that the latter formed larger and longer-lived clusters within mucosal and peripheral lymph nodes. This is the first comparison of the behavior of antigen-specific CD4+ T cells in situ in mucosal and systemic lymphoid tissues during the induction of priming versus tolerance in a physiologically relevant model in vivo

Characterisation of the pathogenic effects of the in vivo expression of an ALS-linked mutation in D-amino acid oxidase: Phenotype and loss of spinal cord motor neurons

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular disorder characterised by selective loss of motor neurons leading to fatal paralysis. Current therapeutic approaches are limited in their effectiveness. Substantial advances in understanding ALS disease mechanisms has come from the identification of pathogenic mutations in dominantly inherited familial ALS (FALS). We previously reported a coding mutation in D-amino acid oxidase (DAOR199W) associated with FALS. DAO metabolises D-serine, an essential co-agonist at the N-Methyl-D-aspartic acid glutamate receptor subtype (NMDAR). Using primary motor neuron cultures or motor neuron cell lines we demonstrated that expression of DAOR199W, promoted the formation of ubiquitinated protein aggregates, activated autophagy and increased apoptosis. The aim of this study was to characterise the effects of DAOR199W in vivo, using transgenic mice overexpressing DAOR199W. Marked abnormal motor features, e.g. kyphosis, were evident in mice expressing DAOR199W, which were associated with a significant loss (19%) of lumbar spinal cord motor neurons, analysed at 14 months. When separated by gender, this effect was greater in females (26%; p< 0.0132). In addition, we crossed the DAOR199W transgenic mouse line with the SOD1G93A mouse model of ALS to determine whether the effects of SOD1G93A were potentiated in the double transgenic line (DAOR199W/SOD1G93A). Although overall survival was not affected, onset of neurological signs was significantly earlier in female double transgenic animals than their female SOD1G93A littermates (125 days vs 131 days, P = 0.0239). In summary, some significant in vivo effects of DAOR199W on motor neuron function (i.e. kyphosis and loss of motor neurons) were detected which were most marked in females and could contribute to the earlier onset of neurological signs in double transgenic females compared to SOD1G93A littermates, highlighting the importance of recognizing gender effects present in animal models of ALS

Emissions and topographic effects on column CO_2 (XCO_2) variations, with a focus on the Southern California Megacity

Within the California South Coast Air Basin (SoCAB), X_(CO)_2 varies significantly due to atmospheric dynamics and the nonuniform distribution of sources. X_(CO)_2 measurements within the basin have seasonal variation compared to the “background” due primarily to dynamics, or the origins of air masses coming into the basin. We observe basin-background differences that are in close agreement for three observing systems: Total Carbon Column Observing Network (TCCON) 2.3 ± 1.2 ppm, Orbiting Carbon Observatory-2 (OCO-2) 2.4 ± 1.5 ppm, and Greenhouse gases Observing Satellite 2.4 ± 1.6 ppm (errors are 1σ). We further observe persistent significant differences (∼0.9 ppm) in X_(CO)_2 between two TCCON sites located only 9 km apart within the SoCAB. We estimate that 20% (±1σ confidence interval (CI): 0%, 58%) of the variance is explained by a difference in elevation using a full physics and emissions model and 36% (±1σ CI: 10%, 101%) using a simple, fixed mixed layer model. This effect arises in the presence of a sharp gradient in any species (here we focus on CO_2) between the mixed layer (ML) and free troposphere. Column differences between nearby locations arise when the change in elevation is greater than the change in ML height. This affects the fraction of atmosphere that is in the ML above each site. We show that such topographic effects produce significant variation in X_(CO)_2 across the SoCAB as well

Emissions and topographic effects on column CO2 (XCO2) variations, with a focus on the Southern California Megacity

Within the California South Coast Air Basin (SoCAB), XCO2 varies significantly due to atmospheric dynamics and the nonuniform distribution of sources. XCO2 measurements within the basin have seasonal variation compared to the “background” due primarily to dynamics, or the origins of air masses coming into the basin. We observe basin‐background differences that are in close agreement for three observing systems: Total Carbon Column Observing Network (TCCON) 2.3 ± 1.2 ppm, Orbiting Carbon Observatory‐2 (OCO‐2) 2.4 ± 1.5 ppm, and Greenhouse gases Observing Satellite 2.4 ± 1.6 ppm (errors are 1σ). We further observe persistent significant differences (∼0.9 ppm) in XCO2 between two TCCON sites located only 9 km apart within the SoCAB. We estimate that 20% (±1σ confidence interval (CI): 0%, 58%) of the variance is explained by a difference in elevation using a full physics and emissions model and 36% (±1σ CI: 10%, 101%) using a simple, fixed mixed layer model. This effect arises in the presence of a sharp gradient in any species (here we focus on CO2) between the mixed layer (ML) and free troposphere. Column differences between nearby locations arise when the change in elevation is greater than the change in ML height. This affects the fraction of atmosphere that is in the ML above each site. We show that such topographic effects produce significant variation in XCO2 across the SoCAB as well.Plain Language SummaryCities persistently have elevated carbon dioxide (CO2) levels as compared to surrounding regions. Within a city CO2 levels can also vary significantly at different locations for reasons such as more CO2 being emitted in some parts than others. Elevated column CO2 levels in the South Coast Air Basin (SoCAB) are in agreement for three observation systems (two satellite and one ground‐based) systems and vary with regional wind patterns throughout the year. In Pasadena, California, within the SoCAB, a significant fraction (about 25%) of variation in the column‐averaged CO2 can be explained by differences in surface altitude. This is important to understand so that all variations in column CO2 within an urban region are not mistakenly interpreted as being from CO2 surface fluxes.Key PointsIn the SoCAB, 20–36% of spatial variance in XCO2 is explained by topography on scales ≲10 kmIn Pasadena, XCO2 is enhanced by 2.3 ± 1.2 (1σ) ppm above background levels, at 1300 (UTC 8) with seasonal variationThe SoCAB XCO2 enhancement is in agreement for 3 different observation sets (TCCON, GOSAT, and OCO‐2)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137737/1/jgrd53887.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137737/2/jgrd53887_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137737/3/jgrd53887-sup-0001-supinfo.pd

Assessing the optimized precision of the aircraft mass balance method for measurement of urban greenhouse gas emission rates through averaging

To effectively address climate change, aggressive mitigation policies need to be implemented to reduce greenhouse gas emissions. Anthropogenic carbon emissions are mostly generated from urban environments, where human activities are spatially concentrated. Improvements in uncertainty determinations and precision of measurement techniques are critical to permit accurate and precise tracking of emissions changes relative to the reduction targets. As part of the INFLUX project, we quantified carbon dioxide (CO2), carbon monoxide (CO) and methane (CH4) emission rates for the city of Indianapolis by averaging results from nine aircraft-based mass balance experiments performed in November-December 2014. Our goal was to assess the achievable precision of the aircraft-based mass balance method through averaging, assuming constant CO2, CH4 and CO emissions during a three-week field campaign in late fall. The averaging method leads to an emission rate of 14,600 mol/s for CO2, assumed to be largely fossil-derived for this period of the year, and 108 mol/s for CO. The relative standard error of the mean is 17% and 16%, for CO2 and CO, respectively, at the 95% confidence level (CL), i.e. a more than 2-fold improvement from the previous estimate of ~40% for single-flight measurements for Indianapolis. For CH4, the averaged emission rate is 67 mol/s, while the standard error of the mean at 95% CL is large, i.e. ±60%. Given the results for CO2 and CO for the same flight data, we conclude that this much larger scatter in the observed CH4 emission rate is most likely due to variability of CH4 emissions, suggesting that the assumption of constant daily emissions is not correct for CH4 sources. This work shows that repeated measurements using aircraft-based mass balance methods can yield sufficient precision of the mean to inform emissions reduction efforts by detecting changes over time in urban emissions

Lentiviral vector preparation for efficient gene and microRNA modulation of peritoneal cavity tissue-resident macrophages in vivo in mice

Peritoneal tissue-resident macrophages have broad functions in the maintenance of homeostasis and are involved in pathologies within local and neighboring tissues. Their functions are dictated by microenvironmental cues; thus, it is essential to investigate their behavior in an in vivo physiological niche. Currently, specific peritoneal macrophage-targeting methodologies employ whole-mouse transgenic models. Here, a protocol for effective in vivo modulation of mRNA and small RNA species (e.g., microRNA) expression in peritoneal macrophages using lentivirus particles is described. Lentivirus preparations were made in HEK293T cells and purified on a single sucrose layer. In vivo validation of lentivirus effectivity following intraperitoneal injection revealed predominant infection of macrophages restricted to local tissue. Targeting of peritoneal macrophages was successful during homeostasis and thioglycolate-induced peritonitis. The limitations of the protocol, including low-level inflammation induced by intraperitoneal delivery of lentivirus and time restrictions for potential experiments, are discussed. Overall, this study presents a quick and accessible protocol for the rapid assessment of gene function in peritoneal macrophages in vivo

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

The Indianapolis Flux Experiment (INFLUX): A test-bed for developing urban greenhouse gas emission measurements

The objective of the Indianapolis Flux Experiment (INFLUX) is to develop, evaluate and improve methods for measuring greenhouse gas (GHG) emissions from cities. INFLUX’s scientific objectives are to quantify CO2 and CH4 emission rates at 1 km2 resolution with a 10% or better accuracy and precision, to determine whole-city emissions with similar skill, and to achieve high (weekly or finer) temporal resolution at both spatial resolutions. The experiment employs atmospheric GHG measurements from both towers and aircraft, atmospheric transport observations and models, and activity-based inventory products to quantify urban GHG emissions. Multiple, independent methods for estimating urban emissions are a central facet of our experimental design. INFLUX was initiated in 2010 and measurements and analyses are ongoing. To date we have quantified urban atmospheric GHG enhancements using aircraft and towers with measurements collected over multiple years, and have estimated whole-city CO2 and CH4 emissions using aircraft and tower GHG measurements, and inventory methods. Significant differences exist across methods; these differences have not yet been resolved; research to reduce uncertainties and reconcile these differences is underway. Sectorally- and spatially-resolved flux estimates, and detection of changes of fluxes over time, are also active research topics. Major challenges include developing methods for distinguishing anthropogenic from biogenic CO2 fluxes, improving our ability to interpret atmospheric GHG measurements close to urban GHG sources and across a broader range of atmospheric stability conditions, and quantifying uncertainties in inventory data products. INFLUX data and tools are intended to serve as an open resource and test bed for future investigations. Well-documented, public archival of data and methods is under development in support of this objective