Defects in Human Methionine Synthase in cblG Patients

Inborn errors resulting in isolated functional methionine synthase deficiency fall into two complementation groups, cblG and cblE. Using biochemical approaches we demonstrate that one cblG patient has greatly reduced levels of methionine synthase while in another, the enzyme is specifically impaired in the reductive activation cycle. The biochemical data suggested that low levels of methionine synthase activity in the first patient may result from mutations in the catalytic domains of the enzyme, reduced transcription, or generation of unstable message or protein. Using Northern analysis, we demonstrate that the molecular basis for the biochemical phenotype in this patient is associated with greatly diminished steady-state levels of methionine synthase mRNA. The biochemical data on the second patient cell line implicated mutations specific to reductive activation, a function that is housed in the C-terminal AdoMet-binding domain and the intermediate B12-binding domain, in the highly homologous bacterial enzyme. We have detected two mutations in a compound heterozygous state, one that results in conversion of a conserved proline (1173) to a leucine residue and the other a deletion of an isoleucine residue (881). The crystal structure of the C-terminal domain of the Escherichia coli MS predicts that the Pro to Leu mutation could disrupt activation since it is embedded in a sequence that makes direct contacts with the bound AdoMet. Deletion of isoleucine in the B12-binding domain would result in shortening of a β-sheet. Our data provide the first evidence for mutations in the methionine synthase gene being culpable for the cblG phenotype. In addition, they suggest directly that mutations in methionine synthase can lead to elevated homocysteine, implicated both in neural tube defects and in cardiovascular disease

A Proposed System for All Weather Attack on Moving Vehicles

Control Systems Laboratory changed its name to Coordinated Science LaboratoryContract DA-11-022-ORD-72

Effect of health promotion and fluoride varnish on dental caries among Australian Aboriginal children: results from a community-randomized controlled trial*

Objectives:  We tested a dental health program in remote Aboriginal communities of Australia’s Northern Territory, hypothesizing that it would reduce dental caries in preschool children. Methods:  In this 2-year, prospective, cluster-randomized, concurrent controlled, open trial of the dental health program compared to no such program, 30 communities were allocated at random to intervention and control groups. All residents aged 18–47 months were invited to participate. Twice per year for 2 years in the 15 intervention communities, fluoride varnish was applied to children’s teeth, water consumption and daily tooth cleaning with toothpaste were advocated, dental health was promoted in community settings, and primary health care workers were trained in preventive dental care. Data from dental examinations at baseline and after 2 years were used to compute net dental caries increment per child (d3mfs). A multi-level statistical model compared d3mfs between intervention and control groups with adjustment for the clustered randomization design; four other models used additional variables for adjustment. Results:  At baseline, 666 children were examined; 543 of them (82%) were re-examined 2 years later. The adjusted d3mfs increment was significantly lower in the intervention group compared to the control group by an average of 3.0 surfaces per child (95% CI = 1.2, 4.9), a prevented fraction of 31%. Adjustment for additional variables yielded caries reductions ranging from 2.3 to 3.5 surfaces per child and prevented fractions of 24–36%. Conclusions:  These results corroborate findings from other studies where fluoride varnish was efficacious in preventing dental caries in young children.Gary D. Slade, Ross S. Bailie, Kaye Roberts-Thomson, Amanda J. Leach, Iris Raye, Colin Endean, Bruce Simmons and Peter Morri

Towards better utilization of NEXRAD data in hydrology: An overview of hydro-NEXRAD

With a very modest investment in computer hardware and the open-source local data manger (LDM) software from UCAR\u27s Unidata Program Center, an individual researcher can receive a variety of NEXRAD Level III gridded rainfall products, and the unprocessed Level II data in real-time from most NEXRAD radars. Additionally, the National Climatic Data Center has vast archives of these products and Level II data. Still, significant obstacles remain in order to unlock the full potential of the data. One set of obstacles is related to effective management of multi-terabyte data sets: storing, compressing, and backing up. A second set of obstacles, for hydrologists and hydrometeorologists in particular, is that the NEXRAD Level III products are not well suited for application in hydrology. There is a strong need for the generation of high-quality products directly from the Level II data with well-documented steps that include quality control, removal of false echoes, rainfall estimation algorithms with variety of corrections, coordinate conversion and georeferencing, conversion to a convenient data format(s), and integration with GIS. For hydrologists it is imperative that these procedures are basin-centered as opposed to radar-centered. Thirdly, the amount of data present in a multi-year, multi-radar dataset is such that simple cataloging and indexing of the data is not sufficient. Rather, sophisticated metadata extraction and management techniques are required. The authors describe and discuss the Hydro-NEXRAD software system that addresses the above three challenges. With support from the National Science Foundation through its ITR program, the authors are developing a basin-centered framework for addressing all these issues in a comprehensive manner, tailored specifically for use of NEXRAD data in hydrology and hydrometeorology. Through a flexible web interface users can search a large metadata database base, managed by a relational database, for subsets of interest. Well-chosen and documented defaults are provided for the flow from unprocessed NEXRAD data to basin-centered rainfall estimates at a desired space-time resolution. In addition to the web interface, there are web services that provide access to scripts and compiled programs. © 2007 ASCE

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded

Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference