Constructing two-sided simultaneous confidence intervals for multinomial proportions for small counts in a large number of cells

Confidence intervals for multinomial proportions are often constructed using large-sample methods that rely on expected cell counts of 5 or greater. In situations that give rise to a large number of categories, the cell counts may not be of adequate size to ensure the appropriate overall coverage probability and alternative methods of construction have been proposed. Sison and Glaz (1995) developed a method of constructing two-sided confidence intervals for multinomial proportions that is based on the doubly truncated Poisson distribution and their method performs well when the cell counts are fairly equally dispersed over a large number of categories. In fact, the Sison and Glaz (1995) intervals appear to outperform other methods of simultaneous construction in terms of coverage probabilities and interval length in these situations. To make the method available to researchers, we have developed a SAS macro to construct the intervals proposed by Sison and Glaz (1995).

A Field Comparison of Fresnel Zone and Ray-Based GPR Attenuation-Difference Tomography for Time-Lapse Imaging of Electrically Anomalous Tracer or Contaminant Plumes

Ground-penetrating radar (GPR) attenuation-difference tomography is a useful tool for imaging the migration of electrically anomalous tracer or contaminant plumes. Attenuation-difference tomography uses the difference in the trace amplitudes of tomographic data sets collected at different times to image the distribution of bulk-conductivity changes within the medium. The most common approach for computing the tomographic sensitivities uses ray theory, which is well understood and leads to efficient computations. However, ray theory requires the assumption that waves propagate at infinite frequency, and thus sensitivities are distributed along a line between the source and receiver. The infinite-frequency assumption in ray theory leads to a significant loss of resolution (both spatially and in terms of amplitude) of the recovered image. We use scattering theory to approximate the sensitivity of electromagnetic (EM) wave amplitude to changes in bulk conductivity within the medium. These sensitivities occupy the first Fresnel zone, account for the finite frequency nature of propagating EM waves, and are valid when velocity variations within the medium do not cause significant ray bending. We evaluate the scattering theory sensitivities by imaging a bromide tracer plume as it migrates through a coarse alluvial aquifer over two successive days. The scattering theory tomograms display a significant improvement in resolution over the ray-based counterparts, as shown by a direct comparison of the tomograms and also by a comparison of the vertical fluid conductivity distribution measured in a monitoring well, located within the tomographic plane. By improving resolution, the scattering theory sensitivities increase the utility of GPR attenuation- difference tomography for monitoring the movement of electrically anomalous plumes. In addition, the improved accuracy of information gathered through attenuation-difference tomography using scattering theory is a positive step toward future developments in using GPR data to help characterize the distribution of hydrogeologic propertie

Applied Remote Sensing Program (ARSP)

There are no author-identified significant results in this report

The TIGA technique for detecting gravitational waves with a spherical antenna

We report the results of a theoretical and experimental study of a spherical gravitational wave antenna. We show that it is possible to understand the data from a spherical antenna with 6 radial resonant transducers attached to the surface in the truncated icosahedral arrangement. We find that the errors associated with small deviations from the ideal case are small compared to other sources of error, such as a finite signal-to-noise ratio. An in situ measurement technique is developed along with a general algorithm that describes a procedure for determining the direction of an external force acting on the antenna, including the force from a gravitational wave, using a combination of the transducer responses. The practicality of these techniques was verified on a room-temperature prototype antenna.Comment: 15 pages, 14 figures, submitted to Physical Review

Neurophysiology

Contains reports on four research projects.Bell Telephone Laboratories, IncorporatedThe Teagle Foundation, IncorporatedNational Science Foundatio

Bone-Associated Gene Evolution and the Origin of Flight in Birds

Background Bones have been subjected to considerable selective pressure throughout vertebrate evolution, such as occurred during the adaptations associated with the development of powered flight. Powered flight evolved independently in two extant clades of vertebrates, birds and bats. While this trait provided advantages such as in aerial foraging habits, escape from predators or long-distance travels, it also imposed great challenges, namely in the bone structure. Results We performed comparative genomic analyses of 89 bone-associated genes from 47 avian genomes (including 45 new), 39 mammalian, and 20 reptilian genomes, and demonstrate that birds, after correcting for multiple testing, have an almost two-fold increase in the number of bone-associated genes with evidence of positive selection (~52.8 %) compared with mammals (~30.3 %). Most of the positive-selected genes in birds are linked with bone regulation and remodeling and thirteen have been linked with functional pathways relevant to powered flight, including bone metabolism, bone fusion, muscle development and hyperglycemia levels. Genes encoding proteins involved in bone resorption, such as TPP1, had a high number of sites under Darwinian selection in birds. Conclusions Patterns of positive selection observed in bird ossification genes suggest that there was a period of intense selective pressure to improve flight efficiency that was closely linked with constraints on body size

FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)

Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening

N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS

Neurophysiology

Contains a report on a research project

Oesophageal varices, schistosomiasis, and mortality among patients admitted with haematemesis in Mwanza, Tanzania: a prospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking. METHODS: We conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa