Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences.

Certain DNA sequences are known to be unusually sensitive to nicking via the Fe2+-mediated Fenton reaction. Most notable are a purine nucleotide followed by three or more G residues, RGGG, and purine nucleotides flanking a TG combination, RTGR. Our laboratory previously demonstrated that nicking in the RGGG sequences occurs preferentially 5' to a G residue with the nicking probability decreasing from the 5' to 3'end of these sequences. Using 1H NMR to characterize Fe2+ binding within the duplex CGAGTTAGGGTAGC/GCTACCCTAACTCG and 7-deazaguanine-containing (Z) variants of it, we show that Fe2+ binds preferentially at the GGG sequence, most strongly towards its 5' end. Substitutions of individual guanines with Z indicate that the high affinity Fe2+ binding at AGGG involves two adjacent guanine N7 moieties. Binding is accompanied by large changes in specific imino, aromatic and methyl proton chemical shifts, indicating that a locally distorted structure forms at the binding site that affects the conformation of the two base pairs 3' to the GGG sequence. The binding of Fe2+ to RGGG contrasts with that previously observed for the RTGR sequence, which binds Fe2+ with negligible structural rearrangements

Inequalities in Health and Service Use among People with Borderline Intellectual Impairment

This report, produced in collaboration with Professor Angela Hassiotis and others, sets out the extent to which people with borderline intellectual impairment face inequalities in health and use of services compared with the rest of the population, and seeks to improve awareness of these inequalities. Findings - Borderline intellectual impairment is common, affecting at least one adult in ten in England. The term is used here to refer to people with good verbal skills and living in private households, but who may experience cognitive impairments. - The findings in this report are consistent with previous research: people with borderline intellectual impairment are a disadvantaged group and their needs are not well understood. - Such adults face high levels of poor mental health, poorer general health, and many limitations in their daily lives. - Their level of use of mental health treatment and services does not appear to be commensurate with their higher level of need. This indicates that they are underserved compared with the rest of the population. - This may be due to a lack of professional awareness of their needs, to services not adapting enough to meet those needs, or to difficulties the individual faces in seeking treatment and support. - Adults with borderline intellectual impairment constitute key users of primary and secondary health care, and employment, education and welfare support. Improving awareness of the needs of this group should form part of wider plans to reduce inequalities in health and service use in England. Methods Secondary analysis of data from the Adult Psychiatric Morbidity Survey (APMS) was conducted to profile the circumstances of people with borderline intellectual impairment. APMS is one of the most authoritative and comprehensive national household surveys to assess both intellectual functioning and mental health in adults in England

Phase 2 of the array automated assembly task for the low cost solar array project

The process sequence for the fabrication of dendritic web silicon into solar panels was modified to include aluminum back surface field formation. Plasma etching was found to be a feasible technique for pre-diffusion cleaning of the web. Several contacting systems were studied. The total plated Pd-Ni system was not compatible with the process sequence; however, the evaporated TiPd-electroplated Cu system was shown stable under life testing. Ultrasonic bonding parameters were determined for various interconnect and contact metals but the yield of the process was not sufficiently high to use for module fabrication at this time. Over 400 solar cells were fabricated according to the modified sequence. No sub-process incompatibility was seen. These cells were used to fabricate four demonstration modules. A cost analysis of the modified process sequence resulted in a selling price of $0.75/peak watt

The origin of grand minima in the sunspot cycle

One of the most striking aspects of the 11-year sunspot cycle is that there have been times in the past when some cycles went missing, a most well-known example of this being the Maunder minimum during 1645-1715. Analyses of cosmogenic isotopes (C14 and Be10) indicated that there were about 27 grand minima in the last 11,000 yr, implying that about 2.7% of the solar cycles had conditions appropriate for forcing the Sun into grand minima. We address the question how grand minima are produced and specifically calculate the frequency of occurrence of grand minima from a theoretical dynamo model. We assume that fluctuations in the poloidal field generation mechanism and the meridional circulation produce irregularities of sunspot cycles. Taking these fluctuations to be Gaussian and estimating the values of important parameters from the data of last 28 solar cycles, we show from our flux transport dynamo model that about 1-4% of the sunspot cycles may have conditions suitable for inducing grand minima.Comment: Accepted for publication in Physical Review Letter