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"Francis, David"
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Wedding Bush Road : a novel
\"A young lawyer in Los Angeles is called back to his family's farm in rural Australia and plunged into a complex struggle between past and present, town and country, and the secrets that haunt them all. When he learns of his mother's ailing health, Daniel Rawson must leave Los Angeles and travel half a world away to the family's horse farm on Wedding Bush Road, one hundred miles outside of Melbourne. Estranged from his parents, Daniel is hesitant to revisit their history: long divorced, his mother still maintains the farm having put out her cheating, rakish husband, and even in these later years her anger burns brightly. Daniel arrives at the farm in the heat of his parents' conflict with Sharen, an alluring tenant and ex-lover of his father now perched on family land. Sharen and her unstable son Reggie complicate an already difficult family dynamic while Daniel has to tend to his mother's condition, his father's contentious behavior, and the swell of memory that strikes whenever he visits the farm. As Daniel is increasingly drawn to Sharen, the various tensions across the farm will spark events that cannot help but change them all\"-- Provided by publisher.
Book
Material design for lymph node drug delivery
A significant fraction of the total immune cells in the body are located in several hundred lymph nodes, in which lymphocyte accumulation, activation and proliferation are organized. Therefore, targeting lymph nodes provides the possibility to directly deliver drugs to lymphocytes and lymph node-resident cells and thus to modify the adaptive immune response. However, owing to the structure and anatomy of lymph nodes, as well as the distinct localization and migration of the different cell types within the lymph node, it is difficult to access specific cell populations by delivering free drugs. Materials can be used as instructive delivery vehicles to achieve accumulation of drugs in the lymph nodes and to target specific lymph node-resident cell subtypes. In this Review, we describe the compartmental architecture of lymph nodes and the cell and fluid transport mechanisms to and from lymph nodes. We discuss the different entry routes into lymph nodes and how they can be explored for drug delivery, including the lymphatics, blood capillaries, high endothelial venules, cell-mediated pathways, homing of circulating lymphocytes and direct lymph node injection. We examine different nanoscale and microscale materials for the targeting of specific immune cells and highlight their potential for the treatment of immune dysfunction and for cancer immunotherapy. Finally, we give an outlook to the field, exploring how lymph node targeting can be improved by the use of materials.
Nanoscale and microscale materials can be used as drug delivery vehicles to target specific lymph node-resident cell subtypes for immunotherapy. In this Review, the authors discuss the transport mechanisms to and from lymph nodes and how they can be explored for drug delivery.
Journal Article
Thermosensitive hydrogel releasing nitric oxide donor and anti-CTLA-4 micelles for anti-tumor immunotherapy
Due to their autosynchronous roles in shaping the anti-tumor immune response, complex immune regulatory networks acting both locally within the tumor microenvironment as well as in its draining lymph nodes play critical roles in the cancer immunotherapy response. We describe herein a thermosensitive co-polymer hydrogel system formed from biocompatible polymers gelatin and Pluronic
®
F127 that are widely used in humans to enable the sustained release of a nitric oxide donor and antibody blocking immune checkpoint cytotoxic T-lymphocyte-associated protein-4 for efficient and durable anti-tumor immunotherapy. By virtue of its unique gel formation and degradation properties that sustain drug retention at the tumor tissue site for triggered release by the tumor microenvironment and formation of in situ micelles optimum in size for lymphatic uptake, this rationally designed thermosensitive hydrogel facilitates modulation of two orthogonal immune signaling networks relevant to the regulation of the anti-tumor immune response to improve local and abscopal effects of cancer immunotherapy.
Nitric oxide exerts a multitude of physiological functions and has also been exploited for anticancer therapies. Here the authors report the design of a micelle-releasing thermosensitive hydrogel system for the concomitant locoregional and lymphatic delivery of a nitric oxide donor and an anti-CTLA4 antibody, showing anti-tumor immune responses in preclinical cancer models.
Journal Article
Development of a Large SNP Genotyping Array and Generation of High-Density Genetic Maps in Tomato
The concurrent development of high-throughput genotyping platforms and next generation sequencing (NGS) has increased the number and density of genetic markers, the efficiency of constructing detailed linkage maps, and our ability to overlay recombination and physical maps of the genome. We developed an array for tomato with 8,784 Single Nucleotide Polymorphisms (SNPs) mainly discovered based on NGS-derived transcriptome sequences. Of the SNPs, 7,720 (88%) passed manufacturing quality control and could be scored in tomato germplasm. The array was used to generate high-density linkage maps for three interspecific F-2 populations: EXPEN 2000 (Solanum lycopersicum LA0925 x S. pennellii LA0716, 79 individuals), EXPEN 2012 (S. lycopersicum Moneymaker x S. pennellii LA0716, 160 individuals), and EXPIM 2012 (S. lycopersicum Moneymaker x S. pimpinellifolium LA0121, 183 individuals). The EXPEN 2000-SNP and EXPEN 2012 maps consisted of 3,503 and 3,687 markers representing 1,076 and 1,229 unique map positions (genetic bins), respectively. The EXPEN 2000-SNP map had an average marker bin interval of 1.6 cM, while the EXPEN 2012 map had an average bin interval of 0.9 cM. The EXPIM 2012 map was constructed with 4,491 markers (1,358 bins) and an average bin interval of 0.8 cM. All three linkage maps revealed an uneven distribution of markers across the genome. The dense EXPEN 2012 and EXPIM 2012 maps showed high levels of colinearity across all 12 chromosomes, and also revealed evidence of small inversions between LA0716 and LA0121. Physical positions of 7,666 SNPs were identified relative to the tomato genome sequence. The genetic and physical positions were mostly consistent. Exceptions were observed for chromosomes 3, 10 and 12. Comparing genetic positions relative to physical positions revealed that genomic regions with high recombination rates were consistent with the known distribution of euchromatin across the 12 chromosomes, while very low recombination rates were observed in the heterochromatic regions.
Journal Article
The devil's diary : Alfred Rosenberg and the stolen secrets of the Third Reich
A \"World War II narrative wrapped in a ... detective story, The Devil's Diary investigates the disappearance of a private diary penned by one of Adolf Hitler's top aides--Alfred Rosenberg, his chief philosopher--and mines its long-hidden pages to deliver [an] ... account of the Nazi rise to power and the genesis of the Holocaust\"--Amazon.com.
Book
Early Detection of Dyslexia Risk
Many states now mandate early screening for dyslexia, but vary in how they address these mandates. There is confusion about the nature of screening versus diagnostic assessments, risk versus diagnosis, concurrent versus predictive validity, and inattention to indices of classification accuracy as the basis for determining risk. To help define what constitutes a screening assessment, we summarize efforts to develop short (3–5 min), teacher-administered screens that used multivariate strategies for variable selection, item response theory to select items that are most discriminating at a threshold for predicting risk, and statistical decision theory. These methods optimize prediction and lower the burden on teachers by reducing the number of items needed to evaluate risk. A specific goal of these efforts was to minimize decision errors that would result in the failure to identify a child as at risk of dyslexia/reading problems (false negatives) despite the inevitable increase in identifications of children who eventually perform in the typical range (false positives). Five screens, developed for different periods during kindergarten, Grade 1, and Grade 2, predicted outcomes measured later in the same school year (Grade 2) or in the subsequent year (Grade 1). The results of this approach to development are applicable to other screening methods, especially those that attempt to predict those children at risk of dyslexia prior to the onset of reading instruction. Without reliable and valid early predictive screening measures that reduce the burden on teachers, early intervention and prevention of dyslexia and related reading problems will be difficult.
Journal Article
Birthplace, migration and crime : the Australian experience
Issues surrounding the migration of human beings are some of the most pressing of our time. Through both historical and contemporary material, this book builds on the author's previous work in the area to explore the landscape of crime and migration in Australia. Focusing primarily upon the Australian experience, but illuminated by studies in other countries and at other times, Professor Francis provides a comprehensive account of crime and migration, linking migration policy with criminality and mental health and arguing that it is birthplace, not race, which impacts upon crimes committed by migrants. Covering a diverse range of issues from the police, courts and prisons to victimology and immigration policy, this book will appeal to scholars across Criminology, Sociology, Law, Migration Studies and Politics.
Book
High-density SNP genotyping of tomato (Solanum lycopersicum L.) reveals patterns of genetic variation due to breeding
The effects of selection on genome variation were investigated and visualized in tomato using a high-density single nucleotide polymorphism (SNP) array. 7,720 SNPs were genotyped on a collection of 426 tomato accessions (410 inbreds and 16 hybrids) and over 97% of the markers were polymorphic in the entire collection. Principal component analysis (PCA) and pairwise estimates of F(st) supported that the inbred accessions represented seven sub-populations including processing, large-fruited fresh market, large-fruited vintage, cultivated cherry, landrace, wild cherry, and S. pimpinellifolium. Further divisions were found within both the contemporary processing and fresh market sub-populations. These sub-populations showed higher levels of genetic diversity relative to the vintage sub-population. The array provided a large number of polymorphic SNP markers across each sub-population, ranging from 3,159 in the vintage accessions to 6,234 in the cultivated cherry accessions. Visualization of minor allele frequency revealed regions of the genome that distinguished three representative sub-populations of cultivated tomato (processing, fresh market, and vintage), particularly on chromosomes 2, 4, 5, 6, and 11. The PCA loadings and F(st) outlier analysis between these three sub-populations identified a large number of candidate loci under positive selection on chromosomes 4, 5, and 11. The extent of linkage disequilibrium (LD) was examined within each chromosome for these sub-populations. LD decay varied between chromosomes and sub-populations, with large differences reflective of breeding history. For example, on chromosome 11, decay occurred over 0.8 cM for processing accessions and over 19.7 cM for fresh market accessions. The observed SNP variation and LD decay suggest that different patterns of genetic variation in cultivated tomato are due to introgression from wild species and selection for market specialization.
Journal Article