Nanoparticles in medicine: Automating the analysis process of high-throughput microscopy data.

Automated tracking of cells across timelapse microscopy image sequences typically employs complex segmentation routines and/or bio-staining of the tracking objective. Often accurate identification of a cell's morphology is not of interest and the accurate segmentation of cells in pursuit of non-morphological parameters is complex and time consuming. This thesis explores the potential of internalized quantum dot nanoparticles as alternative, bio- and photo-stable optical markers for tracking the motions of cells through time. CdTe/ZnS core-shell quantum dots act as nodes in moving light display networks within A549, epithelial, lung cancer cells over a 40 hour time period. These quantum dot fluorescence sources are identified and interpreted using simplistic algorithms to find consistent, non-subjective centroids that represent cell centre locations. The presented tracking protocols yield an approximate 91% success rate over 24 hours and 78% over the full 40 hours. The nanoparticle moving light displays also provide simultaneous collection of cell motility data, resolution of mitotic traversal dynamics and identification of familial relationships enabling the construction of multi-parameter lineage trees. This principle is then developed further through inclusion of 3 different coloured quantum dots to create cell specific colour barcodes and reduce the number of time points necessary to successfully track cells through time. The tracking software and identification of parameters without detailed morphological knowledge is also demonstrated through automated extraction of DOX accumulation profiles and Cobalt agglomeration accruement statistics from two separate toxicology assays without the need for cell segmentation

The Methodology of the Multi-site Study of the Termination of Supplemental Security Income Benefits for Drug Addicts and Alcoholics

This paper describes the quantitative and qualitative methodologies used in a nine-site, two-year study of the effects of terminating Supplemental Security Income (SSI) for drug addiction and alcoholism (DA&A). The quantitative component of the study involved a longitudinal survey that collected data on 1,744 former DA&A recipients, representing about one-fourth of the national population, and achieved an aggregate follow-up rate of 82%. Despite limitations in questionnaire design and implementation, the survey provided reasonably valid data in the following areas: demographics, employment/income, medical/psychiatric status, drug and alcohol use, legal involvement, family/social functioning, food and hunger, housing, and victimization. The qualitative component examined the lives of a subsample to help clarify important issues that could not be addressed within the more structured protocol and format of the longitudinal survey. The paper also presents details on the survey instrument design, the results of validation studies of selected survey items, and data collection protocols across study sites

The Methodology of the Multi-site Study of the Termination of Supplemental Security Income Benefits for Drug Addicts and Alcoholics

This paper describes the quantitative and qualitative methodologies used in a nine-site, two-year study of the effects of terminating Supplemental Security Income (SSI) for drug addiction and alcoholism (DA&A). The quantitative component of the study involved a longitudinal survey that collected data on 1,744 former DA&A recipients, representing about one-fourth of the national population, and achieved an aggregate follow-up rate of 82%. Despite limitations in questionnaire design and implementation, the survey provided reasonably valid data in the following areas: demographics, employment/income, medical/psychiatric status, drug and alcohol use, legal involvement, family/social functioning, food and hunger, housing, and victimization. The qualitative component examined the lives of a subsample to help clarify important issues that could not be addressed within the more structured protocol and format of the longitudinal survey. The paper also presents details on the survey instrument design, the results of validation studies of selected survey items, and data collection protocols across study sites

Conceptual art and artists' books : an Australian perspective

It will be argued in this thesis that Australian conceptual and post-object artists' books established the field of Australian artists' books. From an Australian perspective, this thesis will investigate the international field of practice as it formed within global conceptualism through the period 1963 to 1983. This thesis will specifically examine the conceptual publications produced by expatriate Australian artists from the late 1960s onwards, and the artists' books produced by locally-based Australian post-object artists through the 1970s. This thesis will conclude by demonstrating how by the early 1980s, these conceptual and post-object artists' books produced during the previous two decades had set the material and discursive foundations for the field of Australian artists' books

Drug Treatment Participation and Retention Rates among Former Recipients of Supplemental Security Income for Drug Addiction and Alcoholism

This study examined drug treatment participation and retention rates for a multisite sample of 1,586 former recipients of Supplemental Security Income (SSI) for drug addiction and alcoholism (DA&A). Fewer than half of the sample were complying with the DA&A program treatment mandate at the time the program was terminated by federal legislation in January 1997. For all forms of treatment, both participation and retention rates declined steadily thereafter until fewer than 10% of the total sample reported being in a formal treatment two years after termination of the mandate. Survival analyses comparing treatment retention rates for DA&A beneficiaries with non-DA&A SSI beneficiaries revealed that most of the decline in treatment retention could be attributed to ending the mandate. The findings suggest that although the mandate was often not well enforced, it did bring into drug treatment many individuals who would not otherwise have participated

Drug Treatment Participation and Retention Rates among Former Recipients of Supplemental Security Income for Drug Addiction and Alcoholism

This study examined drug treatment participation and retention rates for a multisite sample of 1,586 former recipients of Supplemental Security Income (SSI) for drug addiction and alcoholism (DA&A). Fewer than half of the sample were complying with the DA&A program treatment mandate at the time the program was terminated by federal legislation in January 1997. For all forms of treatment, both participation and retention rates declined steadily thereafter until fewer than 10% of the total sample reported being in a formal treatment two years after termination of the mandate. Survival analyses comparing treatment retention rates for DA&A beneficiaries with non-DA&A SSI beneficiaries revealed that most of the decline in treatment retention could be attributed to ending the mandate. The findings suggest that although the mandate was often not well enforced, it did bring into drug treatment many individuals who would not otherwise have participated

TgCDPK3 Regulates Calcium-Dependent Egress of Toxoplasma gondii from Host Cells

The phylum Apicomplexa comprises a group of obligate intracellular parasites of broad medical and agricultural significance, including Toxoplasma gondii and the malaria-causing Plasmodium spp. Key to their parasitic lifestyle is the need to egress from an infected cell, actively move through tissue, and reinvade another cell, thus perpetuating infection. Ca(2+)-mediated signaling events modulate key steps required for host cell egress, invasion and motility, including secretion of microneme organelles and activation of the force-generating actomyosin-based motor. Here we show that a plant-like Calcium-Dependent Protein Kinase (CDPK) in T. gondii, TgCDPK3, which localizes to the inner side of the plasma membrane, is not essential to the parasite but is required for optimal in vitro growth. We demonstrate that TgCDPK3, the orthologue of Plasmodium PfCDPK1, regulates Ca(2+) ionophore- and DTT-induced host cell egress, but not motility or invasion. Furthermore, we show that targeting to the inner side of the plasma membrane by dual acylation is required for its activity. Interestingly, TgCDPK3 regulates microneme secretion when parasites are intracellular but not extracellular. Indeed, the requirement for TgCDPK3 is most likely determined by the high K(+) concentration of the host cell. Our results therefore suggest that TgCDPK3's role differs from that previously hypothesized, and rather support a model where this kinase plays a role in rapidly responding to Ca(2+) signaling in specific ionic environments to upregulate multiple processes required for gliding motility.This work was supported by the National Health and Medical Research Council (NHMRC) Project Grant APP1025598. JMM is supported by a Australian Postgraduate Award, GGvD is supported by an Australian Research Council QEII Fellowship and CJT is supported by an NHMRC Career Development Award. This work was also made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Reconstruction of former glacier surface topography from archive oblique aerial images

Archive oblique aerial imagery offers the potential to reconstruct the former geometry of valley glaciers and other landscape surfaces. Whilst the use of Structure-from-Motion (SfM) photogrammetry with multiview stereopsis (MVS) to process small-format imagery is now well established in the geosciences, the potential of the technique for extracting topographic data from archive oblique aerial imagery is unclear. Here, SfM-MVS is used to reconstruct the former topography of two high-Arctic glaciers (Midtre and Austre Lovénbreen, Svalbard, Norway) using three archive oblique aerial images obtained by the Norwegian Polar Institute in 1936. The 1936 point cloud was produced using seven LiDAR-derived ground control points located on stable surfaces in proximity to the former piedmont glacier termini. To assess accuracy, the 1936 data set was compared to a LiDAR data set using the M3C2 algorithm to calculate cloud-to-cloud differences. For stable areas (such as nonglacial surfaces), vertical differences were detected between the two point clouds (RMS M3C2 vertical difference of 8.5 m), with the outwash zones adjacent to the assessed glacier termini showing less extensive vertical discrepancies (94% of M3C2 vertical differences between ±5 m). This research highlights that historical glacier surface topography can be extracted from archive oblique aerial imagery, but accuracy is limited by issues including the lack of camera calibration, the quality and resolution of the archive imagery, and by the identification of suitable ground control. To demonstrate the value of historical glacier surfaces produced using oblique archive imagery, the reconstructed glacier surface topography is used to investigate evidence of a potential former surge front at the high-Arctic valley glacier, Austre Lovénbreen - a glacier identified to have potentially exhibited surge-type behaviour during the Neoglacial. A surface bulge of ~15–20 m is resolved on the 1936 model; however, when compared with the now deglaciated former subglacial topography, a surge origin for the surface feature becomes unclear. The processed 1936 oblique imagery was also used to produce orthorectified nadir aerial imagery, from which structural mapping was undertaken: this adds to the existing 1948–1995 structural map series for these glaciers. This research demonstrates the potential of SfM-MVS for reconstructing historical glacier surfaces, which is important for aiding our understanding of former glacier dynamics and enabling the rapid assessment of glacier change over time

RCandy: an R package for visualizing homologous recombinations in bacterial genomes

SUMMARY: Homologous recombination is an important evolutionary process in bacteria and other prokaryotes, which increases genomic sequence diversity and can facilitate adaptation. Several methods and tools have been developed to detect genomic regions recently affected by recombination. Exploration and visualization of such recombination events can reveal valuable biological insights, but it remains challenging. Here, we present RCandy, a platform-independent R package for rapid, simple and flexible visualization of recombination events in bacterial genomes. AVAILABILITY AND IMPLEMENTATION: RCandy is an R package freely available for use under the MIT license. It is platform-independent and has been tested on Windows, Linux and MacOSX. The source code comes together with a detailed vignette available on GitHub at https://github.com/ChrispinChaguza/RCandy. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online