My Omaha Obsession takes the reader on an idiosyncratic tour through some of Omaha's neighborhoods, buildings, architecture, and people--celebrating the city's unusual and overlooked history.
Invasive alien species are among the primary causes of biodiversity change globally, with the risks thereof broadly understood for most regions of the world. They are similarly thought to be among ...the most significant conservation threats to Antarctica, especially as climate change proceeds in the region. However, no comprehensive, continent-wide evaluation of the risks to Antarctica posed by such species has been undertaken. Here we do so by sampling, identifying, and mapping the vascular plant propagules carried by all categories of visitors to Antarctica during the International Polar Year's first season (2007–2008) and assessing propagule establishment likelihood based on their identity and origins and on spatial variation in Antarctica's climate. For an evaluation of the situation in 2100, we use modeled climates based on the Intergovernmental Panel on Climate Change's Special Report on Emissions Scenarios Scenario A1B Nakićenović N, Swart R, eds (2000) Special Report on Emissions Scenarios: A Special Report of Working Group III of the Intergovernmental Panel on Climate Change (Cambridge University Press, Cambridge, UK). Visitors carrying seeds average 9.5 seeds per person, although as vectors, scientists carry greater propagule loads than tourists. Annual tourist numbers (∼33,054) are higher than those of scientists (∼7,085), thus tempering these differences in propagule load. Alien species establishment is currently most likely for the Western Antarctic Peninsula. Recent founder populations of several alien species in this area corroborate these findings. With climate change, risks will grow in the Antarctic Peninsula, Ross Sea, and East Antarctic coastal regions. Our evidence-based assessment demonstrates which parts of Antarctica are at growing risk from alien species that may become invasive and provides the means to mitigate this threat now and into the future as the continent's climate changes.
Gain-of-function mutations in leucine-rich kinase 2 (LRRK2) are associated with increased incidence of Parkinson disease (PD); thus, pharmacological inhibition of LRRK2 kinase activity is postulated ...as a disease-modifying treatment of PD. Histomorphological changes in lungs of nonhuman primates (NHPs) treated with small-molecule LRRK2 kinase inhibitors have brought the safety of this treatment approach into question. Although it remains unclear how LRRK2 kinase inhibition affects the lung, continued studies in NHPs prove to be both cost- and resource-prohibitive. To develop a tractable alternative animal model platform, we dosed male mice in-diet with the potent, highly selective LRRK2 kinase inhibitor MLi-2 and induced histomorphological changes in lung within 1 week. Oral bolus dosing of MLi-2 at a frequency modeled to provide steady-state exposure equivalent to that achieved with in-diet dosing induced type II pneumocyte vacuolation, suggesting pulmonary changes require sustained LRRK2 kinase inhibition. Treating mice with MLi-2 in-diet for up to 6 months resulted in type II pneumocyte vacuolation that progressed only modestly over time and was fully reversible after withdrawal of MLi-2. Immunohistochemical analysis of lung revealed a significant increase in prosurfactant protein C staining within type II pneumocytes. In the present study, we demonstrated the kinetics for onset, progression, and rapid reversibility of chronic LRRK2 kinase inhibitor effects on lung histomorphology in rodents and provide further evidence for the derisking of safety and tolerability concerns for chronic LRRK2 kinase inhibition in PD. SIGNIFICANCE STATEMENT: We have defined a mouse model by which the on-target lung effects of leucine-rich kinase 2 (LRRK2) kinase inhibition can be monitored, whereas previous in vivo testing relied solely on nonhuman primates. Data serve to derisk long-term treatment with LRRK2 kinase inhibitors, as all lung changes were mild and readily reversible.
Assessment of chromium content in human nail or nail clippings could serve as an effective biomarker of chromium status. The feasibility of a new portable x-ray fluorescence (XRF) approach to ...chromium measurement was investigated through analysis of nail and nail clipping phantoms. Five measurements of 180s (real time) duration were first performed on six whole nail phantoms having chromium concentrations of 0, 2, 5, 10, 15, and 20µg/g. Using nail clippers, these phantoms were then converted to nail clippings, and assembled into different mass groups of 20, 40, 60, 80, and 100mg for additional measurements. The amplitude of the chromium Kα characteristic x-ray energy peak was examined as a function of phantom concentration for all measurement conditions to create a series of calibration lines. The minimum detection limit (MDL) for chromium was also calculated for each case. The chromium MDL determined from the whole nail intact phantoms was 0.88±0.03µg/g. For the clipping phantoms, the MDL ranged from 1.2 to 3.3µg/g, depending on the mass group analyzed. For the 40mg clipping group, the MDL was 1.2±0.1µg/g, and higher mass collections did not improve upon this result. This MDL is comparable to chromium concentration levels seen in various studies involving human nail clippings. Further improvements to the portable XRF technique would be required to detect chromium levels expected from the lower end of a typical population.
•Portable x-ray fluorescence (XRF) was explored as a technique to assess levels of chromium in human nails or nail clippings.•Results were found to depend on the mass of clipping sample provided.•Minimum detection limits for chromium were similar to concentration levels found in previous studies of human nail clippings.
Next-generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were ...confined to triple-negative breast cancers (TNBC; 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with paclitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in patients with TNBC. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD-low tumors without NOTCH1 mutations were resistant.
NOTCH1 mutations, immunohistochemical staining for activated NOTCH1, and HES4 expression are biomarkers that can be used to identify solid tumors that are likely to respond to GSI-based therapies.
•Seeds, bryophytes and lichen fragments are inadvertently introduced in the Antarctic.•Different parts of clothing and gear run different chances to harbour propagules.•Habitats visited earlier may ...increase the transport of propagules.•Encourageing self-assessment of visitors may prevent introduction.
Despite considerable research on biological invasions, key areas remain poorly explored, especially ways to reduce unintentional propagule transfer. The Antarctic represents a microcosm of the situation, with the numbers of established non-native species growing. Information to help reduce potential impacts is therefore critical. We measured the propagule load of seeds, and fragments of bryophytes and lichens (the number of other plant or animal fragments was too low to draw any conclusions) carried in the clothing and gear of visitors to the Antarctic, during the 2007/08 austral summer. Samples were collected from different categories of visitors associated with national research programs and tourism and different categories of clothing and gear, new as well as used. We also collected information about the timing of travel and the regions visitors had travelled to prior to Antarctic travel. Seeds were found in 20% and 45% of tourist and science visitor samples, respectively. For bryophyte and lichen fragments the proportions were 11% and 20%, respectively. Footwear, trousers and bags belonging to field scientists were the highest risk items, especially of those personnel which had previously visited protected areas, parklands/botanic gardens or alpine areas. Tourists who visited rural/agricultural areas prior to travel, and/or travel with national programs or on smaller tourist vessels had the highest probability of transferring plant propagules. Travel either during the boreal or austral autumn months increased the probability of propagule presence. Our assessment is applicable to other areas given evidence of propagule transfer patterns in those areas that are broadly similar to those documented here.
The current work provides a sound evidence base for both self-regulation (e.g. taking care of personal equipment) and organization-based regulation (e.g. issuing guidelines and holding regular inspections) to reduce propagule transfer of plants to the Antarctic.
Land‐use change is one of the biggest threats to biodiversity globally. The effects of land use on biodiversity manifest primarily at local scales which are not captured by the coarse spatial grain ...of current global land‐use mapping. Assessments of land‐use impacts on biodiversity across large spatial extents require data at a similar spatial grain to the ecological processes they are assessing. Here, we develop a method for statistically downscaling mapped land‐use data that combines generalized additive modeling and constrained optimization. This method was applied to the 0.5° Land‐use Harmonization data for the year 2005 to produce global 30″ (approx. 1 km2) estimates of five land‐use classes: primary habitat, secondary habitat, cropland, pasture, and urban. The original dataset was partitioned into 61 bio‐realms (unique combinations of biome and biogeographical realm) and downscaled using relationships with fine‐grained climate, land cover, landform, and anthropogenic influence layers. The downscaled land‐use data were validated using the PREDICTS database and the geoWiki global cropland dataset. Application of the new method to all 61 bio‐realms produced global fine‐grained layers from the 2005 time step of the Land‐use Harmonization dataset. Coarse‐scaled proportions of land use estimated from these data compared well with those estimated in the original datasets (mean R2: 0.68 ± 0.19). Validation with the PREDICTS database showed the new downscaled land‐use layers improved discrimination of all five classes at PREDICTS sites (P < 0.0001 in all cases). Additional validation of the downscaled cropping layer with the geoWiki layer showed an R2 improvement of 0.12 compared with the Land‐use Harmonization data. The downscaling method presented here produced the first global land‐use dataset at a spatial grain relevant to ecological processes that drive changes in biodiversity over space and time. Integrating these data with biodiversity measures will enable the reporting of land‐use impacts on biodiversity at a finer resolution than previously possible. Furthermore, the general method presented here could be useful to others wishing to downscale similarly constrained coarse‐resolution data for other environmental variables.
Current global land‐use data are at a coarse spatial grain which does not match the local ecological processes that they disrupt. Here, we present a new statistical downscaling method and apply this method to a global 0.5 degree land‐use dataset. Using our method, we produce a global fine‐grained land‐use dataset at a spatial resolution more relevant to the local ecological processes that land‐use practices disrupt.
The feasibility of measuring arsenic and selenium contents in a single nail clipping was investigated using a small-focus portable X-ray fluorescence (XRF) instrument with monochromatic excitation ...beams. Nail clipping phantoms supplemented with arsenic and selenium to produce materials with 0, 5, 10, 15, and 20µg/g were used for calibration purposes. In total, 10 different clippings were analyzed at two different measurement positions. Energy spectra were fit with detection peaks for arsenic Kα, selenium Kα, arsenic Kβ, selenium Kβ, and bromine Kα characteristic X-rays. Data analysis was performed under two distinct conditions of fitting constraint. Calibration lines were established from the amplitude of each of the arsenic and selenium peaks as a function of the elemental contents in the clippings. The slopes of the four calibration lines were consistent between the two conditions of analysis. The calculated minimum detection limit (MDL) of the method, when considering the Kα peak only, ranged from 0.210±0.002µg/g selenium under one condition of analysis to 0.777±0.009µg/g selenium under another. Compared with previous portable XRF nail clipping studies, MDLs were substantially improved for both arsenic and selenium. The new measurement technique had the additional benefits of being short in duration (~3min) and requiring only a single nail clipping. The mass of the individual clipping used did not appear to play a major role in signal strength, but positioning of the clipping is important.
•Portable X-ray fluorescence was used to assess As and Se in nail clipping phantoms.•Calibration lines were consistent between two different conditions of data analysis.•This new XRF approach was sensitive and required only a single nail clipping.
Panels and Pens Ware, Chris
PMLA : Publications of the Modern Language Association of America,
05/2019, Letnik:
134, Številka:
3
Journal Article
Recenzirano
As one of the many fortunate and grateful subjects of Hillary Chute's writing over the past few years, I feel ethically compelled to recuse myself from any discourse regarding her most recent book ...simply because it would seem, well, unsightly. (And in comics, where reading and seeing operate at parity, being unsightly is patently undesirable.) Here's what I
can
tell you, though: She
gets
it. And she gets it right. There are few, if any, other writers on comics who so minutely and more thoroughly understand the psychological, aesthetic and perceptual complexities of deploying images as words and drawing as writing—but then quickly go beyond all that stuff to get at the human and humane essence of the works considered. Because comics are essentially just another mode of storytelling, stories are almost always Hillary's focus, and I've known her long enough now—about a dozen years—to know she also believes that of all stories, life itself is the most important one. I'm glad she's ended up being a part of mine, and that, in print, she's also a part of yours.
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