A preliminary assessment of water partitioning and ecohydrological coupling in northern headwaters using stable isotopes and conceptual runoff models

Funded by European Research Council ERC. Grant Number: GA 335910 VEWA Swedish Science Foundation (SITES) Future Forest Formas (ForWater) SKB the Kempe foundation Environment Canada the Garfield Weston Foundation the Natural Sciences and Engineering Research Council of Canada (NSERC) the Northwest Territories Cumulative Impacts Monitoring ProgramPeer reviewedPublisher PD

Stream Centric Methods for Determining Groundwater Contributions in Karst Mountain Watersheds

Climate change influences on mountain hydrology are uncertain but likely to be mediated by variability in subsurface hydrologic residence times and flow paths. The heterogeneity of karst aquifers adds complexity in assessing the resiliency of these water sources to perturbation, suggesting a clear need to quantify contributions from and losses to these aquifers. Here we develop a stream centric method that combines mass and flow balances to quantify net and gross gains and losses at different spatial scales. We then extend these methods to differentiate between karst conduit and matrix contributions from the aquifer. In the Logan River watershed in Northern Utah we found significant amounts of the river water repeatedly gained and then lost through a 35‐km study reach. Further, the direction and amount of water exchanged varied over space, time, and discharge. Streamflow was dominated by discharge of karst conduit groundwater after spring runoff with increasing, yet still small, fractions of matrix water later in the summer. These findings were combined with geologic information, prior subsurface dye tracing, and chemical sampling to provide additional lines of evidence that repeated groundwater exchanges are likely occurring and river flows are highly dependent on karst aquifer recharge and discharge. Given the large population dependent on karst aquifers throughout the world, there is a continued need to develop simple methods, like those presented here, for determining the resiliency of karst groundwater resources

Variation of organic matter quantity and quality in streams at Critical Zone Observatory watersheds

The quantity and chemical composition of dissolved organic matter (DOM) in surface waters influence ecosystem processes and anthropogenic use of freshwater. However, despite the importance of understanding spatial and temporal patterns in DOM, measures of DOM quality are not routinely included as part of large-scale ecosystem monitoring programs and variations in analytical procedures can introduce artifacts. In this study, we used consistent sampling and analytical methods to meet the objective of defining variability in DOM quantity and quality and other measures of water quality in streamflow issuing from small forested watersheds located within five Critical Zone Observatory sites representing contrasting environmental conditions. Results show distinct separations among sites as a function of water quality constituents. Relationships among rates of atmospheric deposition, water quality conditions, and stream DOM quantity and quality are consistent with the notion that areas with relatively high rates of atmospheric nitrogen and sulfur deposition and high concentrations of divalent cations result in selective transport of DOM derived from microbial sources, including in-stream microbial phototrophs. We suggest that the critical zone as a whole strongly influences the origin, composition, and fate of DOM in streams. This study highlights the value of consistent DOM characterization methods included as part of long-term monitoring programs for improving our understanding of interactions among ecosystem processes as controls on DOM biogeochemistry

MEMS Deformable Mirrors for Space-Based High-Contrast Imaging

Micro-Electro-Mechanical Systems (MEMS) Deformable Mirrors (DMs) enable precise wavefront control for optical systems. This technology can be used to meet the extreme wavefront control requirements for high contrast imaging of exoplanets with coronagraph instruments. MEMS DM technology is being demonstrated and developed in preparation for future exoplanet high contrast imaging space telescopes, including the Wide Field Infrared Survey Telescope (WFIRST) mission which supported the development of a 2040 actuator MEMS DM. In this paper, we discuss ground testing results and several projects which demonstrate the operation of MEMS DMs in the space environment. The missions include the Planet Imaging Concept Testbed Using a Recoverable Experiment (PICTURE) sounding rocket (launched 2011), the Planet Imaging Coronagraphic Technology Using a Reconfigurable Experimental Base (PICTURE-B) sounding rocket (launched 2015), the Planetary Imaging Concept Testbed Using a Recoverable Experiment - Coronagraph (PICTURE-C) high altitude balloon (expected launch 2019), the High Contrast Imaging Balloon System (HiCIBaS) high altitude balloon (launched 2018), and the Deformable Mirror Demonstration Mission (DeMi) CubeSat mission (expected launch late 2019). We summarize results from the previously flown missions and objectives for the missions that are next on the pad. PICTURE had technical difficulties with the sounding rocket telemetry system. PICTURE-B demonstrated functionality at >100 km altitude after the payload experienced 12-g RMS (Vehicle Level 2) test and sounding rocket launch loads. The PICTURE-C balloon aims to demonstrate 10(-7) contrast using a vector vortex coronagraph, image plane wavefront sensor, and a 952 actuator MEMS DM. The HiClBaS flight experienced a DM cabling issue, but the 37-segment hexagonal piston-tip-tilt DM is operational post-flight. The DeMi mission aims to demonstrate wavefront control to a precision of less than 100 nm RMS in space with a 140 actuator MEMS DM.DARPA; NASA Space Technology Research FellowshipOpen Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Combating subclonal evolution of resistant cancer phenotypes

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these phenotypes pre-exist in pre-treatment subclones that become dominant after chemotherapy, indicating selection for resistance phenotypes. Post-chemotherapy cancer cells are effectively treated with drugs targeting acquired phenotypes. These findings highlight cancer's ability to evolve phenotypically and suggest a phenotype-targeted treatment strategy that adapts to cancer as it evolves

Genetic counselling and testing in pulmonary arterial hypertension:a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.</p

Maturation-Dependent Licensing of Naive T Cells for Rapid TNF Production

The peripheral naïve T cell pool is comprised of a heterogeneous population of cells at various stages of development, which is a process that begins in the thymus and is completed after a post-thymic maturation phase in the periphery. One hallmark of naïve T cells in secondary lymphoid organs is their unique ability to produce TNF rapidly after activation and prior to acquiring other effector functions. To determine how maturation influences the licensing of naïve T cells to produce TNF, we compared cytokine profiles of CD4+ and CD8+ single positive (SP) thymocytes, recent thymic emigrants (RTEs) and mature-naïve (MN) T cells during TCR activation. SP thymocytes exhibited a poor ability to produce TNF when compared to splenic T cells despite expressing similar TCR levels and possessing comparable activation kinetics (upregulation of CD25 and CD69). Provision of optimal antigen presenting cells from the spleen did not fully enable SP thymocytes to produce TNF, suggesting an intrinsic defect in their ability to produce TNF efficiently. Using a thymocyte adoptive transfer model, we demonstrate that the ability of T cells to produce TNF increases progressively with time in the periphery as a function of their maturation state. RTEs that were identified in NG-BAC transgenic mice by the expression of GFP showed a significantly enhanced ability to express TNF relative to SP thymocytes but not to the extent of fully MN T cells. Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass