Advanced software techniques for space shuttle data management systems Final report

Airborne/spaceborn computer design and techniques for space shuttle data management system

A model for the distribution of aftershock waiting times

In this work the distribution of inter-occurrence times between earthquakes in aftershock sequences is analyzed and a model based on a non-homogeneous Poisson (NHP) process is proposed to quantify the observed scaling. In this model the generalized Omori's law for the decay of aftershocks is used as a time-dependent rate in the NHP process. The analytically derived distribution of inter-occurrence times is applied to several major aftershock sequences in California to confirm the validity of the proposed hypothesis.Comment: 4 pages, 3 figure

Microchamber Cultures of Bladder Cancer: A Platform for Characterizing Drug Responsiveness and Resistance in PDX and Primary Cancer Cells.

Precision cancer medicine seeks to target the underlying genetic alterations of cancer; however, it has been challenging to use genetic profiles of individual patients in identifying the most appropriate anti-cancer drugs. This spurred the development of patient avatars; for example, patient-derived xenografts (PDXs) established in mice and used for drug exposure studies. However, PDXs are associated with high cost, long development time and low efficiency of engraftment. Herein we explored the use of microfluidic devices or microchambers as simple and low-cost means of maintaining bladder cancer cells over extended periods of times in order to study patterns of drug responsiveness and resistance. When placed into 75 µm tall microfluidic chambers, cancer cells grew as ellipsoids reaching millimeter-scale dimeters over the course of 30 days in culture. We cultured three PDX and three clinical patient specimens with 100% success rate. The turn-around time for a typical efficacy study using microchambers was less than 10 days. Importantly, PDX-derived ellipsoids in microchambers retained patterns of drug responsiveness and resistance observed in PDX mice and also exhibited in vivo-like heterogeneity of tumor responses. Overall, this study establishes microfluidic cultures of difficult-to-maintain primary cancer cells as a useful tool for precision cancer medicine

Equifinality and preservation potential of complex eskers

Eskers are useful for reconstructing meltwater drainage systems of glaciers and ice sheets. However, our process understanding of eskers suffers from a disconnect between sporadic detailed morpho‐sedimentary investigations of abundant large‐scale ancient esker systems, and a small number of modern analogues where esker formation has been observed. This paper presents the results of detailed field and high‐resolution remote sensing studies into two esker systems that have recently emerged at Hørbyebreen, Svalbard, and one at Breiðamerkurjökull, Iceland. Despite the different glaciological settings (polythermal valley glacier vs. active temperate piedmont lobe), in all cases a distinctive planform morphology has developed, where ridges are orientated in two dominant directions corresponding to the direction of ice flow and the shape of the ice margin. These two orientations in combination form a cross‐cutting and locally rectilinear pattern. One set of ridges at Hørbyebreen is a hybrid of eskers and geometric ridges formed during a surge and/or jökulhlaup event. The other sets of ridges are eskers formed time‐transgressively at a retreating ice margin. The similar morphology of esker complexes formed in different ways on both glacier forelands implies equifinality, meaning that care should be taken when interpreting Quaternary esker patterns. The eskers at Hørbyebreen contain substantial ice‐cores with a high ice:sediment ratio, suggesting that they would be unlikely to survive after ice melt. The Breiðamerkurjökull eskers emerged from terrain characterized by buried ice that has melted out. Our observations lead us to conclude that eskers may reflect a wide range of processes at dynamic ice margins, including significant paraglacial adjustments. This work, as well as previous studies, confirms that constraints on esker morphology include: topographic setting (e.g. confined valley or broad plain); sediment and meltwater availability (including surges and jökulhlaups); position of formation (supraglacial, englacial or subglacial); and ice‐marginal dynamics such as channel abandonment, the formation of outwash heads or the burial and/or exhumation of dead ice

Environmental DNA analysis as an emerging non-destructive method for plant biodiversity monitoring: a review

Environmental DNA (eDNA) analysis has recently transformed and modernized biodiversity monitoring. The accurate detection, and to some extent quantification, of organisms (individuals/populations/communities) in environmental samples is galvanizing eDNA as a successful cost and time-efficient biomonitoring technique. Currently, eDNA’s application to plants remains more limited in implementation and scope compared to animals and microorganisms. Thus, this review evaluates the development of eDNA-based methods for (vascular) plants, comparing its performance and power of detection with that of traditional methods, to critically evaluate and advise best practices needed for innovating plant biomonitoring. Recent advancements, standardization, and field applications of eDNA-based methods have provided enough scope to utilize it in conservation biology for numerous organisms. eDNA also has considerable potential for plants, where successful detection of invasive, endangered and rare species, and community-level interpretations have provided proof-of-concept. Monitoring methods using eDNA were found to be equal or more effective than traditional methods, however species detection increased when both the methods were coupled. Additionally, eDNA methods were found to be effective in studying species interactions, community dynamics, and even effects of anthropogenic pressure. Currently, elimination of potential obstacles (e.g., lack of relevant DNA reference libraries for plants) and the development of user-friendly protocols would greatly contribute to comprehensive eDNA-based plant monitoring programs. This is particularly needed in the data-depauperate tropics and for some less-concern plant groups. We further advocate it may be valuable to couple traditional methods with eDNA approaches, as the former is often cheaper and methodologically more straightforward, while the latter offers a non-destructive approach with the ability to identify plants in situations where morphological identification is difficult or impossible. Furthermore, in order to make a global platform for eDNA, governmental and academic-industrial collaborations are essential to make eDNA surveys a broadly adopted and implemented, rapid, cost-effective, and non-invasive plant monitoring approach

DNA barcoding the native flowering plants and conifers of Wales

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification

Molecular Dynamics Studies of Dislocations in CdTe Crystals from a New Bond Order Potential

Cd1-xZnxTe (CZT) crystals are the leading semiconductors for radiation detection, but their application is limited by the high cost of detector-grade materials. High crystal costs primarily result from property non-uniformity that causes low manufacturing yield. While tremendous efforts have been made in the past to reduce Te inclusions / precipitates in CZT, this has not resulted in an anticipated improvement in material property uniformity. Moreover, it is recognized that in addition to Te particles, dislocation cells can also cause electric field perturbation and the associated property non-uniformity. Further improvement of the material, therefore, requires that dislocations in CZT crystals be understood and controlled. Here we use a recently developed CZT bond order potential to perform representative molecular dynamics simulations to study configurations, energies, and mobilities of 29 different types of possible dislocations in CdTe (i.e., x = 1) crystals. An efficient method to derive activation free energies and activation volumes of thermally activated dislocation motion will be explored. Our focus gives insight into understanding important dislocations in the material, and gives guidance toward experimental efforts for improving dislocation network structures in CZT crystals

Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.

Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research. FASEB J 2018 Mar; 32(3):1537-1549

Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season

Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health

This is the final version. Available on open access from Elsevier via the DOI in this recordData and Code Availability Statement: Data collected using qPCR is archived and on NERC EIDC [https://doi.org/10.5285/28208be4-0163-45e6-912c-2db205126925]. Standard pollen monitoring ‘count’ data were sourced from the MEDMI database, with the exception of data from Bangor which were produced as part of the present study and are available on request. Prescribing datasets are publicly available, as are weather, air pollution, deprivation (IMD) and rural-urban category data. Hospital episode statistics (HES) datasets are sensitive, individual-level health data, which are subject to strict privacy regulations and are not publicly available. The study did not generate any unique codeGrass (Poaceae) pollen is the most important outdoor aeroallergen, exacerbating a range of respiratory conditions, including allergic asthma and rhinitis (‘hay fever’). Understanding the relationships between respiratory diseases and airborne grass pollen with view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis and over 300 million with asthma, globally, often comorbidly . In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017). The relative contributions of the >11,000 (worldwide) grass species to respiratory health have been unresolved, as grass pollen cannot be readily discriminated using standard microscopy. Instead, here we used novel environmental DNA (eDNA) sampling and quantitative PCR (qPCR) , to measure the relative abundances of airborne pollen from common grass species, during two grass pollen seasons (2016 and 2017), across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalised additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.Natural Environment Research Council (NERC)National Institute for Health Research (NIHR)Public Health EnglandUniversity of ExeterUniversity College LondonMet Offic