A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

Improving Behaviour in Schools: Evidence Review

This is the final version. Available from the Education Endowment Foundation via the link in this record"Improving Behaviour in Schools: Guidance Report" is available in ORE at http://hdl.handle.net/10871/37789Education Endowment Foundatio

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

The UK Environmental Change Network datasets – integrated and co-located data for long-term environmental research (1993–2015)

Long-term datasets of integrated environmental variables, co-located together, are relatively rare. The UK Environmental Change Network (ECN) was launched in 1992 and provides the UK with its only long-term integrated environmental monitoring and research network for the assessment of the causes and consequences of environmental change. Measurements, covering a wide range of physical, chemical, and biological “driver” and “response” variables are made in close proximity at ECN terrestrial sites using protocols incorporating standard quality control procedures. This paper describes the datasets (there are 19 published ECN datasets) for these co-located measurements, containing over 20 years of data (1993–2015). The data and supporting documentation are freely available from the NERC Environmental Information Data Centre under the terms of the Open Government Licence (see paper for DOIs)

Conformations of Linear DNA

We examine the conformations of a model for under- and overwound DNA. The molecule is represented as a cylindrically symmetric elastic string subjected to a stretching force and to constraints corresponding to a specification of the link number. We derive a fundamental relation between the Euler angles that describe the curve and the topological linking number. Analytical expressions for the spatial configurations of the molecule in the infinite- length limit were obtained. A unique configuraion minimizes the energy for a given set of physical conditions. An elastic model incorporating thermal fluctuations provides excellent agreement with experimental results on the plectonemic transition.Comment: 5 pages, RevTeX; 6 postscript figure

UK Environmental Change Network stakeholder consultation

During the Environmental Change Network (ECN) site mangers meeting feedback on the role of UK-SCAPE funding was sought. Representatives from collaborating institutions did not restrict their comments to only the period of UK-SCAPE, as this program is a continuation of previous national capability funding. The stakeholders present appreciated the role of UKCEH through the processes of co-design, co-delivery and co-development in shaping the ECN. They further commented on the co-dependency conferred by the network for their institutions and sites. While several stakeholders noted that they could not benefit directly from UK-SCAPE funding they recognised that funding was required for coordination of the network in addition to collecting monitoring data. They highlighted the risk of failure of the network and the lost opportunities in terms of collaborative working and data delivery to the research community if funding is not maintained in the network

Hydrology and water quality of a field and riparian buffer adjacent to a mangrove wetland in Jobos Bay watershed, Puerto Rico

Agriculture in coastal areas of Puerto Rico is often adjacent to or near mangrove wetlands. Riparian buffers, while they may also be wetlands, can be used to protect mangrove wetlands from agricultural inputs of sediment, nutrients, and pesticides. We used simulation models and field data to estimate the water, nitrogen, and phosphorus inputs from an agricultural field and riparian buffer to a mangrove wetland in Jobos Bay watershed, Puerto Rico. We used the Agricultural Policy/Environmental eXtender (APEX) and the Riparian Ecosystem Management Model (REMM) models sequentially to simulate the hydrology and water quality of the agricultural fields and an adjacent riparian buffer, respectively. Depth to the water table surface was measured monthly at numerous sites in both field and riparian areas and were used with recording well data from outside the field to estimate daily water table depths in the field and riparian buffer and to calibrate field-scale hydrologic processes. Calibration and validation of the models were successful for the riparian buffer and in three of four field quadrants. In these areas the average simulated depth to water table for the field and the riparian buffer were within ±7% of field estimated water table depths. Over the 3-year study period, the riparian buffer represented by REMM reduced agricultural loadings to the mangrove wetland by 24% for sediment yield, and about 30% for total nitrogen and phosphorus. Simulations indicated that tropical storms and hurricanes played an important role in water and nutrient transport on this site contributing at least 63% of total sediment and nutrient loads

A Mobile Prenatal Care App to Reduce In-Person Visits: Prospective Controlled Trial.

BACKGROUND: Risk-appropriate prenatal care has been asserted as a way for the cost-effective delivery of prenatal care. A virtual care model for prenatal care has the potential to provide patient-tailored, risk-appropriate prenatal educational content and may facilitate vital sign and weight monitoring between visits. Previous studies have demonstrated a safe reduction in the frequency of in-person prenatal care visits among low-risk patients but have noted a reduction in patient satisfaction. OBJECTIVE: The primary objective of this study was to test the effectiveness of a mobile prenatal care app to facilitate a reduced in-person visit schedule for low-risk pregnancies while maintaining patient and provider satisfaction. METHODS: This controlled trial compared a control group receiving usual care with an experimental group receiving usual prenatal care and using a mobile prenatal care app. The experimental group had a planned reduction in the frequency of in-person office visits, whereas the control group had the usual number of visits. The trial was conducted at 2 diverse outpatient obstetric (OB) practices that are part of a single academic center in Washington, DC, United States. Women were eligible for enrollment if they presented to care in the first trimester, were aged between 18 and 40 years, had a confirmed desired pregnancy, were not considered high-risk, and had an iOS or Android smartphone that they used regularly. We measured the effectiveness of a virtual care platform for prenatal care via the following measured outcomes: the number of in-person OB visits during pregnancy and patient satisfaction with prenatal care. RESULTS: A total of 88 patients were enrolled in the study, 47 in the experimental group and 41 in the control group. For patients in the experimental group, the average number of in-person OB visits during pregnancy was 7.8 and the average number in the control group was 10.2 (P=.01). There was no statistical difference in patient satisfaction (P\u3e.05) or provider satisfaction (P\u3e.05) in either group. CONCLUSIONS: The use of a mobile prenatal care app was associated with reduced in-person visits, and there was no reduction in patient or provider satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914301; https://clinicaltrials.gov/ct2/show/NCT02914301 (Archived by WebCite at http://www.webcitation.org/76S55M517)