Iron oxide particles for atheroma imaging

The selection of patients for vascular interventions has been solely based on luminal stenosis and symptomatology. However, histological data from both the coronary and carotid vasculature suggest that other plaque features such as inflammation may be more important in predicting future thromboembolic events. Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents have been used for noninvasive MRI assessment of atherosclerotic plaque inflammation in humans. It has reached the stage of development to have been recently used in an interventional drug study to not only assess inflammatory progression but also select patients at high risk. This article reviews the basic science behind the use of USPIO contrast agents in atheroma MR imaging, experimental work in animals, and how this has led to the emergence of this promising targeted imaging platform for assessment of high risk carotid atherosclerosis in humans.

An optimal design for screening trials

Yao, Begg, and Livingston (1996, Biometrics 52, 992-1001) considered the optimal group size for testing a series of potentially therapeutic agents to identify a promising one as soon as possible for given error rates. The number of patients to be tested with each agent was fixed as the group size. We consider a sequential design that allows early acceptance and rejection, and we provide an optimal strategy to minimize the sample sizes (patients) required using Markov decision processes. The minimization is under the constraints of the two types (false positive and false negative) of error probabilities, with the Lagrangian multipliers corresponding to the cost parameters for the two types of errors. Numerical studies indicate that there can be a substantial reduction in the number of patients required.

Dependence of low-lying energy eigenvalues on the short- and long-range parts of confining potentials

The potential description of a quark-antiquark system seems to work very well in describing a number of hadronic properties. However, the precise form of the potential is unknown. The changes in the low-lying eigenvalues as a result of changes in the long-range part of the potential are investigated in a non-perturbative manner. It is shown by considering a variety of examples that the low-lying eigenvalues are insensitive to the long-range part of the potential.

Native cut foliage production using Proteaceae species - A research summary

The Queensland Department of Primary Industries and Fisheries in collaboration with the Rural Industries Research and Development Corporation and Yuruga Nursery Pty Ltd have been conducting research into the development of five native foliage products. The three species and two cultivars being developed for commercial production are: Grevillea baileyana, Lomatia fraxinifolia, Athertonia diversifolia, Stenocarpus 'Forest Lace' and Stenocarpus 'Forest Gem'. Previous research involved an evaluation of 21 species from which these five were selected based on market comments, post harvest life and ability to grow under a range of climatic conditions. Lomatia fraxinifolia, Grevillea baileyana and Athertonia diversifolia are all native to north Queensland rainforests. Stenocarpus 'Forest Gem' and Stenocarpus 'Forest Lace' are hybrids and have been selected by Yuruga Nursery Pty Ltd. Both Stenocarpus cultivars are protected by Plant Breeders Rights. Current research into the commercial development of these species involves: market research, post harvest trials, field trials and grower training. Two field trials have been established on the Atherton Tablelands, one in the high rainfall zone at Yungaburra and the other in the low rainfall zone west of Mareeba. Field trials will evaluate the effects of fertiliser rates and pruning techniques on yield. Pests and diseases will be identified and appropriate control measures tested on trial plants. Vase life evaluations have also been carried out and the results indicate that the five foliages have exceptional vase life. All five products are being sold on the Australian domestic market in small volumes at this stage; it is anticipated that sales will significantly increase in the coming years. A number of leading exporters have indicated that the foliages may also meet the requirements of export markets. Stenocarpus 'Forest Gem' is similar in appearance to Persoonia longifolia (Barker Bush), which is a bush-picked foliage currently exported from Australia to a number of overseas markets.

Crystallographic and modelling studies on Mycobacterium tuberculosis RuvA: Additional role of RuvB-binding domain and inter species variability

RuvA, along with RuvB, is involved in branch migration of heteroduplex DNA in homologous recombination. The structures of three new crystal forms of RuvA from Mycobacterium tuberculosis (MtRuvA) have been determined. The RuvB-binding domain is cleaved off in one of them. Detailed models of the complexes of octameric RuvA from different species with the Holliday junction have also been constructed. A thorough examination of the structures presented here and those reported earlier brings to light the hitherto unappreciated role of the RuvB-binding domain in determining inter-domain orientation and oligomerization. These structures also permit an exploration of the interspecies variability of structural features such as oligomerization and the conformation of the loop that carries the acidic pin, in terms of amino acid substitutions. These models emphasize the additional role of the RuvB-binding domain in Holliday junction binding. This role along with its role in oligomerization could have important biological implications.

Digital Commons Introduction

Presentation given on January 19th, 2005 by Jeff Riedel at the Catherwood Library.

Fundamental Principles and Rights At Work: Value, Viability, Incidence and Importance as Elements For Economic Progress and Social Justice

Working Paper prepared for the ILO by Maria Luz Vega Ruiz and Daniel Martinez, focusing on the rights at work in Latin America and the Caribbean.

BLS Publications, 1972-77, Bulletin 1990

The catalog contain listings for BLS publications from 1972-77. Numerical listings for BLS Bulletins and Reports as well as subject indexes for these and other BLS publications are included.

Temporal patterns in incidence and abundance of Aconophora compressa (Hemiptera: Membracidae), a biological control agent for Lantana camara, on target and nontarget plants

The membracid Aconophora compressa Walker, a biological control agent released in 1995 to control Lantana camara (Verbenaceae) in Australia, has since been collected on several nontarget plant species. Our survey suggests that sustained populations of A. compressa are found only on the introduced nontarget ornamental Citharexylum spinosum (Verbenaceae) and the target weed L. camara. It is found on other nontarget plant species only when populations on C. spinosum and L. camara are high, suggesting that the presence of populations on nontarget species may be a spill-over effect. Some of the incidence and abundance on nontarget plants could have been anticipated from host specificity studies done on this agent before release, whereas others could not. This raises important issues about predicting risks posed by weed biological control agents and the need for long-term postintroduction monitoring on nontarget species.

Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies.

Gene expression evidence for off-target effects caused by RNA interference-mediated gene silencing of Ubiquitin-63E in the cattle tick Rhipicephalus microplus.

Knowledge of cattle tick (Rhipicephalus (Boophilus) microplus; Acari: Ixodidae) molecular and cellular pathways has been hampered by the lack of an annotated genome. In addition, most of the tick expressed sequence tags (ESTs) available to date consist of similar to 50% unassigned sequences without predicted functions. The most common approach to address this has been the application of RNA interference (RNAi) methods to investigate genes and their pathways. This approach has been widely adopted in tick research despite minimal knowledge of the tick RNAi pathway and double-stranded RNA (dsRNA) uptake mechanisms. A strong knockdown phenotype of adult female ticks had previously been observed using a 594 bp dsRNA targeting the cattle tick homologue for the Drosophila Ubiquitin-63E gene leading to nil or deformed eggs. A NimbleGen cattle tick custom microarray based on the BmiGI.V2 database of R. microplus ESTs was used to evaluate the expression of mRNAs harvested from ticks treated with the tick Ubiquitin-63E 594 bp dsRNA compared with controls. A total of 144 ESTs including TC6372 (Ubiquitin-63E) were down-regulated with 136 ESTs up-regulated following treatment. The results obtained substantiated the knockdown phenotype with ESTs identified as being associated with ubiquitin proteolysis as well as oogenesis, embryogenesis, fatty acid synthesis and stress responses. A bioinformatics analysis was undertaken to predict off-target effects (OTE) resulting from the in silico dicing of the 594 bp Ubiquitin-63E dsRNA which identified 10 down-regulated ESTs (including TC6372) within the list of differentially expressed probes on the microarrays. Subsequent knockdown experiments utilising 196 and 109 bp dsRNAs, and a cocktail of short hairpin RNAs (shRNA) targeting Ubiquitin-63E, demonstrated similar phenotypes for the dsRNAs but nil effect following shRNA treatment. Quantitative reverse transcriptase PCR analysis confirmed differential expression of TC6372 and selected ESTs. Our study demonstrated the minimisation of predicted OTEs in the shorter dsRNA treatments (similar to 100-200 bp) and the usefulness of microarrays to study knockdown phenotypes.

Genome-wide linkage analysis of multiple measures of neuroticism of 2 large cohorts from Australia and the Netherlands

CONTEXT People meeting diagnostic criteria for anxiety or depressive disorders tend to score high on the personality scale of neuroticism. Studying this personality dimension can give insights into the etiology of these important psychiatric disorders. OBJECTIVES To undertake a comprehensive genome-wide linkage study of neuroticism using large study samples that have been measured multiple times and to compare the results between countries for replication and across time within countries for consistency. DESIGN Genome-wide linkage scan. SETTING Twin individuals and their family members from Australia and the Netherlands. PARTICIPANTS Nineteen thousand six hundred thirty-five sibling pairs completed self-report questionnaires for neuroticism up to 5 times over a period of up to 22 years. Five thousand sixty-nine sibling pairs were genotyped with microsatellite markers. METHODS Nonparametric linkage analyses were conducted in MERLIN-REGRESS for the mean neuroticism scores averaged across time. Additional analyses were conducted for the time-specific measures of neuroticism from each country to investigate consistency of linkage results. RESULTS Three chromosomal regions exceeded empirically derived thresholds for suggestive linkage using mean neuroticism scores: 10p 5 Kosambi cM (cM) (Dutch study sample), 14q 103 cM (Dutch study sample), and 18q 117 cM (combined Australian and Dutch study sample), but only 14q retained significance after correction for multiple testing. These regions all showed evidence for linkage in individual time-specific measures of neuroticism and 1 (18q) showed some evidence for replication between countries. Linkage intervals for these regions all overlap with regions identified in other studies of neuroticism or related traits and/or in studies of anxiety in mice. CONCLUSIONS Our results demonstrate the value of the availability of multiple measures over time and add to the optimism reported in recent reviews for replication of linkage regions for neuroticism. These regions are likely to harbor causal variants for neuroticism and its related psychiatric disorders and can inform prioritization of results from genome-wide association studies.