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Search Results: 1 - 10 of 28680 matches for " Robert Clarke "
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The Internet of Things and Next-generation Public Health Information Systems  [PDF]
Robert Steele, Andrew Clarke
Communications and Network (CN) , 2013, DOI: 10.4236/cn.2013.53B1002
Abstract: The Internet of things has particularly novel implications in the area of public health. This is due to (1) The rapid and widespread adoption of powerful contemporary Smartphone’s; (2) The increasing availability and use of health and fitness sensors, wearable sensor patches, smart watches, wireless-enabled digital tattoos and ambient sensors; and (3) The nature of public health to implicitly involve connectivity with and the acquisition of data in relation to large numbers of individuals up to population scale. Of particular relevance in relation to the Internet of Things (IoT) and public health is the need for privacy and anonymity of users. It should be noted that IoT capabilities are not inconsistent with maintaining privacy, due to the focus of public health on aggregate data not individual data and broad public health interventions. In addition, public health information systems utilizing IoT capabilities can be constructed to specifically ensure privacy, security and anonymity, as has been developed and evaluated in this work. In this paper we describe the particular characteristics of the IoT that can play a role in enabling emerging public health capabilities; we describe a privacy-preserving IoT-based public health information system architecture; and provide a privacy evaluation.
Cannibalism, cell survival, and endocrine resistance in breast cancer
Robert Clarke
Breast Cancer Research , 2011, DOI: 10.1186/bcr2870
Abstract: Approximately 70% of newly diagnosed breast cancers express detectable levels of estrogen receptor alpha (ERα). Patients with these tumors generally receive an endocrine-based intervention, usually in the form of an aromatase inhibitor or antiestrogen. While these interventions are associated with a significant increase in overall survival [1], many ERα-positive breast cancers recur.Breast cancer cells often respond to endocrine therapies by altering the expression of a subset of estrogen-responsive and nonresponsive genes and inducing autophagy [2-7]. Autophagy is a lysosomal self-digestion pathway, where selected subcellular components are first segregated into double membrane-bound structures called autophagosomes [8]. Subsequent fusion with lysosomes forms autolysosomes, which enables the materials sequestered therein to be digested by lysosomal hydrolases. Three primary forms of autophagy have been described: macroautophagy, microautophagy, and chaperone-mediated autophagy. The comments in this viewpoint relate primarily to macroautophagy.Autophagy can be prodeath or prosurvival and reflects an attempt by stressed cells to eliminate damaged or other organelles and recover the energy stored in their macromolecules to restore metabolic homeostasis. Autophagy can result from activation of the unfolded protein response (UPR) [9] in response to the metabolic stress of endocrine therapies [4]. In endocrine manipulated cells, prosurvival autophagy signaling is driven at least partly by UPR activation of the unconventional splicing of the estrogen-responsive XBP1 mRNA [3,10] and, downstream, increased expression of BCL2 family members including BCL2 and BCLW (BCL2L2) [11]. Prodeath signaling can involve induction of a caspasedependent apoptotic cell death (programmed cell death 1) [12] when there is adequate energy, and an autophagy-associated necrotic cell death that is probably energy independent [11]. An autophagic cell death, often referred to as programmed cell de
Complementary yet distinct roles for oestrogen receptor-α and oestrogen receptor-β in mouse mammary epithelial proliferation
Robert B Clarke
Breast Cancer Research , 2004, DOI: 10.1186/bcr795
Abstract: Ovariectomised mice were used to examine the proliferative effects for 48 hours following treatment with E2, TAM or BAG. The halogenated thymidine analogue bromodeoxyuridine (BrdU) was used to label cells in S-phase 0 and 24 hours into the treatment and tissues were collected at 48 hours. This permitted the number of proliferative mammary epithelial cells that accumulated over the 48-hour treatment period to be examined. Surprisingly, all three compounds induced similar numbers of BrdU-labelled cells suggesting that TAM acts as an agonist on the mammary glands of ovariectomised mice and that BAG can elicit proliferation via ERβ. The authors concluded that both ERα and ERβ can mediate the proliferative effects of E2 on the mouse mammary epithelium.Over the same time period, and also in mice treated continuously for 3 weeks, the effect of E2 and TAM on steroid receptor expression was examined using immunohistochemistry and Western blotting. ERα was clearly shown to be down-regulated by E2 in both wild type and ERβ KO animals, but little effect on ERβ or the E2-regulated gene, progesterone receptor (PR), expression could be demonstrated. Interestingly, TAM differed from E2 in that it had little effect on ERα expression, but reduced ERβ expression by about half. Over the 48 hours following injection of E2, the cell cycle-associated protein cyclin D1 accumulated and then disappeared from cell nuclei with similar kinetics to the loss and re-expression of ERα.These latter data provided the rationale for a reexamination of the relationship between proliferating cells and ERα or PR expression. When BrdU-labelling was carried out shortly before removing and processing the tissue for immunohistochemistry, no association between expression of either ERα or PR and BrdU uptake could be demonstrated. However, when labelling was carried out 2 days prior to analysis, about 20% of BrdU-positive cells were PR-positive. This result suggests that these dually labelled cells are daughter
Prefrontal inhibition of threat processing reduces working memory interference
Robert Clarke,Tom Johnstone
Frontiers in Human Neuroscience , 2013, DOI: 10.3389/fnhum.2013.00228
Abstract: Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference.
22nd Annual San Antonio Breast Cancer Symposium, 8-11 December 1999, San Antonio, Texas, USA
Robert B Clarke, Elizabeth Anderson
Breast Cancer Research , 2000, DOI: 10.1186/bcr46
Abstract: Barry Gusterson (Institute of Cancer Research, London, UK) outlined the current understanding of stem cells and the biology of human breast development. The location of stem cells in the human breast remains uncertain, but extrapolation of the results of studies on the mouse mammary gland suggests that 1 in 1000 cells can be classed as progenitors and must be regarded as targets for neoplastic transformation. Ablation of stem cells is an important goal of breast cancer prevention and treatment strategies, and it was good to hear that this area has been prioritized for funding by the US National Cancer Institute. The mouse mammary gland is becoming increasingly important as a model in which the effects of altering single genes on the biology of breast and breast tumour development can be studied. Jeff Rosen (Baylor College of Medicine, Houston, USA) described experiments that showed important interactions between the BRCA1 and TP53 tumour suppressor genes in breast tumour formation. Conditional deletion of the Brca1 gene from the mouse mammary gland resulted in developmental abnormalities and, eventually, the development of p53-null tumours. Crossing the conditional Brca1-knockout mice into a p53-null background greatly accelerated the formation of tumours that were strongly reminiscent of human ductal carcinoma in situ (DCIS). Other knockout studies described by Jeff Rosen have shown a key role for the transcription factor C/EBPβ in mouse mammary gland differentiation. The mammary glands from mice lacking c/ebpβ showed abnormalities in ductal morphogenesis and were unable to lactate. In another experiment, the introduction of a dominant-negative C/EBPβ transgene, liver inhibitory protein, enhanced proliferation and the formation of pre-neoplastic lesions. Interestingly, liver inhibitory protein was overexpressed in 23% of human invasive ductal carcinomas, in which it was associated with a poorer prognosis.The oestrogen receptor (ER) is a major target of current brea
Epithelial stem cells in the mammary gland: casting light into dark corners
Elizabeth Anderson, Robert B Clarke
Breast Cancer Research , 1999, DOI: 10.1186/bcr5
Abstract: Kordon and Smith [1] have refined a widely used model of transplanting mouse mammary epithelium into the cleared mammary fat pads of syngeneic or athymic nude mice [2], and have shown that just one cell can give rise to a complete and fully functional gland. To reach this remarkable conclusion, Kordon and Smith took advantage of the CzechII mouse strain. Like other strains, these mice become infected congenitally with the mouse mammary tumour virus (MMTV) through milk [3]. Unlike other strains, however, the CzechII mice have no endogenous MMTV-like sequences in their genome, so viral insertions can be detected by Southern analysis as long as a large enough number of cells contain the same insertion. The only way that this can happen is if the population being analyzed is clonal, and thus use of the CzechII mice represents an elegant advance on previous methods for detecting transplanted populations in cleared mammary fat pads.Accordingly, Kordon and Smith [1] took small fragments of mammary epithelium from CzechII MMTV-infected mice and transplanted them into cleared mammary fat pads of syngeneic hosts. These hosts were mated and 1 day after parturition about 80% of each of the reconstituted glands was removed for analysis, leaving the remainder intact for subsequent serial transplantation. As expected, most of the transplanted epithelial fragments expanded during pregnancy to become complete and functional mammary glands. If these glands had been derived from several different progenitors, no clear pattern of MMTV-insertional events would have been detected. If, on the other hand, the outgrowths were clonal a distinct and easily detected pattern of MMTV insertion sites would have been seen, as was the case in 20 of the 30 different outgrowths examined by Southern analysis. As a control, the intact contralateral glands of the host mice were analyzed in the same way and, as would be expected for a polyclonal tissue derived from several progenitors, no clear pattern o
Plasma dark matter direct detection
Jackson D. Clarke,Robert Foot
Physics , 2015,
Abstract: Dark matter in spiral galaxies like the Milky Way may take the form of a dark plasma. Hidden sector dark matter charged under an unbroken $U(1)'$ gauge interaction provides a simple and well defined particle physics model realising this possibility. The assumed $U(1)'$ neutrality of the Universe then implies (at least) two oppositely charged dark matter components with self-interactions mediated via a massless "dark photon" (the $U(1)'$ gauge boson). In addition to nuclear recoils such dark matter can give rise to keV electron recoils in direct detection experiments. In this context, the detailed physical properties of the dark matter plasma interacting with the Earth is required. This is a complex system, which is here modelled as a fluid governed by the magnetohydrodynamic equations. These equations are numerically solved for some illustrative examples, and implications for direct detection experiments discussed. In particular, the analysis presented here leaves open the intriguing possibility that the DAMA annual modulation signal is due primarily to electron recoils (or even a combination of electron recoils and nuclear recoils). The importance of diurnal modulation (in addition to annual modulation) as a means of probing this kind of dark matter is also emphasised.
Do early premalignant changes in normal breast epithelial cells predict cancer development?
Robert B Clarke, Nigel J Bundred
Breast Cancer Research , 2004, DOI: 10.1186/bcr967
Abstract: The aetiology of breast cancer is complex but involves selection of variant cells that develop a growth advantage over and above that of the surrounding normal epithelium. The growth advantage must be a combination of increased proliferation and decreased apoptosis to allow cell survival. Comparison of normal breast tissue around cancer with breast reduction derived epithelium [1] indicated that it is mainly decreased apoptosis rather than increased proliferation that is seen in the normal epithelium in malignant breasts. Bypassing senescence and inhibiting apoptosis permits the accumulation of genomic alterations that push a cell toward a malignant phenotype.A recent report from Crawford and coworkers [2] compared genes expressed in normal and variant human mammary epithelial cells (HMECs). It identified that, as well as silencing the INK4a gene through promoter methylation, the variant cells over-express cyclo-oxygenase (COX)-2.Primary culture of breast tissue from normal women yields HMECs, which senesce after 10–15 population doublings in culture. However, a subpopulation termed variant HMECs are capable of proliferating for an additional 30–50 generations, and reach a plateau of high proliferation and high apoptosis termed agonescence in which the cell population does not increase but sustains itself.Nearly 100% of these variant HMECs exhibit telomeric dysfunction and chromosomal defects as they approach agonescence. Many of these defects are similar to those seen in the earliest lesions of breast malignancy, and Crawford and coworkers have already described this variant HMEC population to contain cells with hypermethylated INK4a promoter sequences, which leads to loss of p16INK4A protein and allows increased cell cycling through cyclin D1. The variant HMECs also over-express the COX-2 protein.One limitation in relating variant HMECs to premalignant lesions in vivo is that there is no cell purification step during isolation of HMECs and it is well recognized th
Digital Narrative and the Humanities: An Evaluation of the Use of Digital Storytelling in an Australian Undergraduate Literary Studies Program
Robert Garth Hipkins Clarke,Sharon Thomas
Higher Education Studies , 2012, DOI: 10.5539/hes.v2n3p30
Abstract: A growing number of university teachers advocate the benefits of multimedia and digital technologies in their classrooms. Such technologies are promoted: as a means to ensure the relevance of subject disciplines; and, as tools of engagement to assist students to meet their learning outcomes. Digital storytelling or narration is one example of how educators can utilise technology to introduce innovative teaching methods. In its broadest sense, digital narration involves using digital resources in learning environments for the production by students of multimedia narratives. This paper reports on the results, over a two-year period, of an evaluation of the use of digital narratives in an advanced undergraduate unit on contemporary Australian literature in one Australian university. The evaluation explored students’ and the teacher’s experiences of digital storytelling. In particular, it examined participants’ satisfaction with and anxieties about the use of digital narratives. It also considered the issues that the use of digital narratives raises vis-à-vis the constructive alignment with the themes, aims, and objectives of the unit, as well as the kinds and levels of technical training and assistance required to support students and staff. The results of this evaluation will be of interest to academics considering the use of multimedia technologies in their undergraduate classes.
Habitat protection for sensitive species: Balancing species requirements and human constraints using bioindicators as examples  [PDF]
Joanna Burger, Michael Gochfeld, Charles W. Powers, Lawrence Niles, Robert Zappalorti, Jeremy Feinberg, James Clarke
Natural Science (NS) , 2013, DOI: 10.4236/ns.2013.55A007
Abstract: Vertebrates have particular habitat needs as a function of life cycle and reproductive stage. This paper uses four species as examples to illustrate a paradigm of environmental assessment that includes physical, biological, toxicological and human dimensions. Species used include Chinook salmon (Oncorhynchus tshawytscha), northern leopard frog (Rana pipiens), northern pine snake (Pituophis m. melanoleucus), and red knot (Calidris canutus rufa, a sandpiper). The life cycles of these species include reliance on habitats that are aquatic, terrestrial, aerial, or combinations of these. Two species (frog, snake) are sedentary and two (salmon, sandpiper) are long-distance migrants. While some measurement endpoints are similar for all species (reproductive success, longevity, contaminant loads), others vary depending upon life cycle and habitat. Salmon have a restricted breeding habitat requiring coarse sand, moderate current, and high oxygen levels for adequate egg incubation. Leopard frogs require still water of appropriate temperature for development of eggs. Pine snakes require sand compaction sufficient to sustain a nest burrow without collapsing, and full sun penetration to the sand to allow their eggs in underground nests to incubate and hatch. Red knots migrate to high Arctic tundra, but incubate their own eggs, so temperature is less of a constraint, but feedinging habitat is. These habitat differences suggest the measurement endpoints that are essential to assess habitat suitability and to manage habitats to achieve stable and sustainable populations. Habitat use and population stability have implications for human activities for some, but not all species. Salmon are important economically, recreationally, and as part of Native American culture and diet. Red knots are of interest to people mainly because of their long, intercontinental migrations and declining populations. Other measurement endpoints for these four species illustrate the differences and similarities in metrics necessary to assess habitat needs. The implications of these differences are discussed.
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