Microarray-based ultra-high resolution discovery of genomic deletion mutations

BACKGROUND: Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low. RESULTS: Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size. CONCLUSIONS: Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence

Two Decades of Income Inequality in Britain: The Role of Wages, Household Earnings and Redistribution

We study earnings and income inequality in Britain over the past two decades, including the period of relatively 'inclusive' growth from 1997 to 2004, and the Great Recession. We focus on the middle 90%, where trends have contrasted strongly with the 'new inequality' at the very top. Household earnings inequality has risen, driven by male earnings-although a 'catch-up' of female earnings did hold down individual earnings inequality and reduce within-household inequality. Nevertheless, net household income inequality fell due to deliberate increases in redistribution, the tax and transfer system's insurance role during the Great Recession, falling household worklessness, and rising pensioner incomes

A review of quantitative structure-activity relationship modelling approaches to predict the toxicity of mixtures

Exposure to chemicals generally occurs in the form of mixtures. However, the great majority of the toxicity data, upon which chemical safety decisions are based, relate only to single compounds. It is currently unfeasible to test a fully representative proportion of mixtures for potential harmful effects and, as such, in silico modelling provides a practical solution to inform safety assessment. Traditional methodologies for deriving estimations of mixture effects, exemplified by principles such as concentration addition (CA) and independent action (IA), are limited as regards the scope of chemical combinations to which they can reliably be applied. Development of appropriate quantitative structure-activity relationships (QSARs) has been put forward as a solution to the shortcomings present within these techniques – allowing for the potential formulation of versatile predictive tools capable of capturing the activities of a full contingent of possible mixtures. This review addresses the current state-of-the-art as regards application of QSAR towards mixture toxicity, discussing the challenges inherent in the task, whilst considering the strengths and limitations of existing approaches. Forty studies are examined within – through reference to several characteristic elements including the nature of the chemicals and endpoints modelled, the form of descriptors adopted, and the principles behind the statistical techniques employed. Recommendations are in turn provided for practices which may assist in further advancing the field, most notably with regards to ensuring confidence in the acquired predictions.publishedVersio

The impact of undergraduate degrees on early-career earnings

This report uses the new Longitudinal Educational Outcomes (LEO) administrative dataset to provide the latest estimates of the impact of Higher Education (HE) on individuals’ early-career earnings after accounting for individuals’ pre-university characteristics. This will provide vital evidence for prospective students choosing whether, where and what to study at university

Reducing Departure Delays for Adjacent Center Airports using Time-Based Flow Management Scheduler: Checkbox On or Off?

The Federal Aviation Administration (FAA) has enhanced the Time-Based Flow Management (TBFM) scheduling tool with a "Checkbox ON" vs. "OFF" function which allows Traffic Management Coordinators (TMCs) to make room in a crowded arrival stream for a departure. When scheduling a departure, having the checkbox ON can delay the Scheduled Times of Arrivals (STAs) of the airborne flights upstream of the TBFM freeze horizons and can compress these flights to their minimum required spacing, thereby creating a slot for a departure. Hence, having the checkbox ON can reduce the frequent ground delays of aircraft departing near high volume airports but can increase delays for airborne arrivals. A Human-in-the-Loop (HITL) simulation compared arrival and departure delays to Newark Airport (EWR) with the checkbox ON vs. OFF as the default position. Three other conditions in this HITL involved various National Airspace System (NAS)-wide approaches for timely delivery of aircraft to the TBFM region. These conditions were: Baseline, using current Mile-in-Trail (MIT) spacing restrictions; Integrated Demand Management (IDM), where all aircraft were given departure times (Expect Departure Clearance Times, or EDCTs), ultimately based on the EWR Airport Arrival Rate; and IDM plus Required Time of Arrival (RTA), a flight deck tool which allowed some aircraft to meet a controlled time of arrival to the TBFM area more precisely. Results showed that the checkbox tool was powerful: with the checkbox ON, departure delays decreased and airborne delays increased, as predicted. However, assuming that the cost ratio of a minute of airborne delay to a minute of departure delay is in the range of 1.2 to 3, as commonly indicated by the literature, checkbox ON and checkbox OFF conditions showed approximately equal total delay costs, i.e., the cost of delays in the air balanced the cost of the delay on the ground. The three scheduling conditions also had approximately equal total delay costs, although a simulation artifact may have reduced the delays in the Baseline condition. In the debrief following the simulation, the TMCs concluded that the checkbox should be used flexibly depending on the current delay situation, and suggested modifications to the checkbox tool which would help them use it in this way, along with enhanced training. The relatively similar total cost of both checkbox default options in this simulation indicates that this might be a fruitful approach, and replace the necessity to have the checkbox rigidly set to either ON or OFF

Transfer of Basic Sciences Knowledge in a Problem‐Based Learning Curriculum

12 months embargo applie

Two-Photon Interferometry for High-Resolution Imaging

We discuss advantages of using non-classical states of light for two aspects of optical imaging: creating of miniature images on photosensitive substrates, which constitutes the foundation for optical lithography, and imaging of micro objects. In both cases, the classical resolution limit given by the Rayleigh criterion is approximately a half of the optical wavelength. It has been shown, however, that by using multi-photon quantum states of the light field, and multi-photon sensitive material or detector, this limit can be surpassed. We give a rigorous quantum mechanical treatment of this problem, address some particularly widespread misconceptions and discuss the requirements for turning the research on quantum imaging into a practical technology.Comment: Presented at PQE 2001. To appear in Special Issue of Journal of Modern Optic