Exploration, quantification, and mitigation of systematic error in high-throughput approaches to gene-expression profiling: implications for data reproducibility

Technological and methodological advances in the fields of medical and life-sciences have, over the last 25 years, revolutionised the way in which cellular activity is measured at the molecular level. Three such advances have provided a means of accurately and rapidly quantifying mRNA, from the development of quantitative Polymerase Chain Reaction (qPCR), to DNA microarrays, and second-generation RNA-sequencing (RNA-seq). Despite consistent improvements in measurement precision and sample throughput, the data generated continue to be a ffected by high levels of variability due to the use of biologically distinct experimental subjects, practical restrictions necessitating the use of small sample sizes, and technical noise introduced during frequently complex sample preparation and analysis procedures. A series of experiments were performed during this project to pro le sources of technical noise in each of these three techniques, with the aim of using the information to produce more accurate and more reliable results. The mechanisms for the introduction of confounding noise in these experiments are highly unpredictable. The variance structure of a qPCR experiment, for example, depends on the particular tissue-type and gene under assessment while expression data obtained by microarray can be greatly influenced by the day on which each array was processed and scanned. RNA-seq, on the other hand, produces data that appear very consistent in terms of differences between technical replicates, however there exist large differences when results are compared against those reported by microarray, which require careful interpretation. It is demonstrated in this thesis that by quantifying some of the major sources of noise in an experiment and utilising compensation mechanisms, either pre- or post-hoc, researchers are better equipped to perform experiments that are more robust, more accurate, and more consistent

The application of chiroptical spectroscopy (circular dichroism) in quantifying binding events in lanthanide directed synthesis of chiral luminescent self-assembly structures

The binding of asymmetrical and optically pure tridentate ligands (L = 1(S) and 1(R)) containing one carboxylic group and 2-naphthyl as an antenna to lanthanide ions (M = La(III) and Eu(III)) was studied in CH3CN, showing the successive formation of M:L, M:L2 and M:L3 stoichiometric species in solution. The europium complexes EuL3 were also synthesised, structurally characterised and their photophysical properties probed in CH3OH and CH3CN. The changes in the chiroptical properties of both 1(S) and 1(R) were used (by circular dichroism (CD) spectroscopy) to monitor the formation of these chiral selfassemblies in solution. While circularly polarised luminescence (CPL) showed the formation of Eu(1(S))3 and Eu(1(R))3 as enantiomers, with high luminescence dissymmetry factors (glum), fitting the CD changes allowed for binding constants to be determined that were comparable to those seen in the analyses of absorbance and luminescence changes

Introducing Big Sagebrush into a Crested Wheatgrass Monoculture

Crested wheatgrass (Agropyron desertorum or A. cristatum) has been effectively used to stabilize arid and semi-arid range sites for decades. Reestablishing native plant materials into these areas is often desirable to increase wildlife habitat and ecological diversity. Due to its competitive nature, efforts to reestablish native plants into crested wheatgrass monocultures have had limited success. Tillage will control the grass but leaves the soil vulnerable to erosion and weed invasion. This publication will report on a trial conducted near Nephi, Utah to find a method of introducing native plants into a crested wheatgrass monoculture without subjecting the resource base to degradation in the conversion process. In this trial, the effect of chemically controlling crested wheatgrass before transplanting big sagebrush (Artemisia tridentata) was studied. Small container grown plants of sagebrush were transplanted either directly into a 60 year-old stand of crested wheatgrass or after chemically controlling the grass. Three different subspecies of big sagebrush; Basin big sagebrush (Artemisia tridentata Nutt. ssp. tridentata), Mountain big sagebrush (Artemisia tridentata Nutt. ssp. vaseyana (Rydb.) Beetle) and Wyoming big sagebrush (Artemisia tridentata Nutt. ssp. wyomingensis Beetle & Young); were planted to see if there would be differences among subspecies. Four years of data indicate that controlling crested wheatgrass prior to transplanting resulted in higher sagebrush survival and faster establishment. There were some differences among sagebrush subspecies. Basin big sagebrush survived equally well with or without grass control but grew faster with grass control. Chemical control of the grass was important for both the survival and growth of Mountain big sage and Wyoming big sage

Review roundtable: naked diplomacy: power and statecraft in the digital age by Tom Fletcher

What is the role of the diplomat in the digital age? In Naked Diplomacy: Power and Statecraft in the Digital Age, Tom Fletcher – former British ambassador to Lebanon and the youngest to be appointed in 200 years – draws upon his own experiences to outline a progressive vision of contemporary diplomacy that challenges top-down or one-way models of communication between diplomats and citizens to instead focus on direct engagement through the use of tools such as social media. In this review roundtable, introduced by LSE’s Nicholas Kitchen, five experts – Alexis Wichowski, Lina Khatib, Iver Neumann, Alaa Murabit and Robert Kelley – respond to Fletcher’s vision of a ‘naked diplomacy’ for the 21st century

Self‐Reported Health and Safety Awareness Improves Prediction of Level of Care Needs in Veterans Discharged From a Postacute Unit

ObjectivesTo evaluate the differential value of a self‐reported health and safety awareness measure relative to other medical, psychosocial, and cognitive factors in predicting level of care (LOC) needs after hospital discharge.DesignRetrospective medical record review.SettingCommunity living center postacute care (CLC‐PAC) unit at a Veterans Affairs hospital.ParticipantsA total of 175 veterans admitted to the Veterans Affairs hospital or directly to the CLC‐PAC from home.MethodsCognitive status was assessed with the Mini‐Mental State Examination, Digit Span Backward subtest, Trail Making Test (Part B), and Hopkins Verbal Learning Test‐Revised. Self‐report of health and safety awareness was measured with the Independent Living Scales Health and Safety (ILS‐HS) subscale. Additional demographic and admission‐related variables were coded, along with medical comorbidity, with the Charlson Comorbidity Index and depression using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision Depression Checklist.Main Outcome MeasurementsIncreased level of care was collected from social work and occupational therapy notes and defined as increased assistance with activities of daily living or nursing home placement comparing prehospitalization with CLC‐PAC discharge.ResultsA total of 19% (n = 34) of residents required increased LOC on CLC‐PAC discharge. The ILS‐HS was a significant predictor of increased LOC above and beyond age and Mini Mental Status Examination score; for each standard deviation decrease in ILS‐HS, there was an increased likelihood of greater LOC (odds ratio 0. 54, 95% confidence interval 0.35‐0.83). Other neuropsychological tests (memory, executive functioning) did not significantly improve the model.ConclusionsThe inclusion of the ILS‐HS to a standard cognitive screen (Mini Mental Status Examination) can improve prediction of increased LOC. Although select aspects of memory and executive functioning independently contribute to increased LOC prediction, the ILS‐HS likely measures a unique aspect of cognitive functioning that may be specific to discharge planning needs in CLC‐PAC residents.Level of EvidenceIIPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146814/1/pmr21122.pd

Role of inherent soil characteristics in assessing soil health across Missouri

Soil health indicator values vary based on parent material, native vegetation, and other soil forming factors; therefore, useful interpretations require consideration of inherent soil characteristics. Our objective was to evaluate the distribution of soil health indicators across soil and climate gradients throughout the state of Missouri through a statewide cover crop cost-share program. Soil samples (0–7 cm) were collected from 5,300 agricultural fields and analyzed for several soil health indicators. Comparisons were made among six regions in the state based on Major Land Resource Area and county boundaries. Results varied for soil organic carbon (C), active C, potentially mineralizable nitrogen, water stable aggregates, and cation exchange capacity by region and corresponded with soil forming factors. Interpretation of soil health indicators must account for regional factors, recognizing that areas with different inherent values have a different potential for soil health

Environmental Implications of Increased Bioenergy Production on Midwest Soil Landscapes [abstract]

Only abstract of poster available.Track III: Energy InfrastructurePrairie soil landscapes encompass over 16 million acres in Missouri and surrounding states. Much of this area has been degraded by erosion but is still used for grain production. Erosion has caused variable topsoil depth within fields which in turn has resulted in greater within-field variability of crop yield, magnified the drought-prone nature of these soils, and lowered the overall soil productivity and ecosystem function. In recent years, pressure on these sensitive soils has risen due to higher demand for grain production, in part for ethanol and biodiesel. In some areas, highly erodible fields which were historically managed as CRP and pasture are being turned into grain crop acres. Thus as new and fluctuating feed and bioenergy markets develop, land management practices will also shift, resulting in changes in soil and water quality of watersheds. This presentation will explore the likely environmental implications of different types of bioenergy production on the soil resource. Further, the positive benefits of potential changes in land use will be in explored. For example, one alternative for sensitive soils is production of perennial grass as a feedstock for coal co-burning plants and for potential future use in cellulosic ethanol production. Perennial grass yields are likely to be less variable than grain yields, both year-to-year and within fields, primarily because of greater resistance to drought. Grass production systems also provide environmental services not obtained from annual grain crops. We will also discuss our work on developing ways to target the most appropriate places in the landscape for grain or perennial production so as to enhance ecosystem services and improve soil and water quality