460 research outputs found

    The Book of Ruth: Solidarity, Kindness, and Peace

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    I propose a reading of The Book of Ruth that takes seriously the pastoral concern for refugees, migrants, and their families that was embodied in the life and teaching of Pope John Paul II.The Book of Ruth models virtues and practices that can help build up a society in solidarity, kindness, and peace. Ruth’s decision to stand beside Naomi demonstrates the value of solidarity in creating a hopeful future for families and communities. Naomi’s role in bringing Ruth and Boaz together shows prudence and a sense of responsibility for shaping the common good. As for Boaz, he is an exemplary model of generosity and kindness. With respect to peacemaking, The Book of Ruth shows how enmity and distrust between nations might be overcome, with God’s hel

    Reflections on a Lifetime of Reading

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    Here I give an account of my life as a reader. The first books I remember enjoying are those that were read aloud on Captain Kangaroo, such as Mike Mulligan and His Steam Shovel, The Story about Ping, and Stone Soup. When I was a little older, in school we learned about science and current events from the stories in Weekly Reader. This was followed by an interest in baseball and the sports page in the local newspaper. In high school, I was more interested in films than books, but “visual literacy” has it place in life, too. My reading in college reading included poems by Wendell Berry, short stories by Flannery O’Connor, and The Plague by Albert Camus. Today I am often called upon to search archival collections for primary documents and photographs that have a bearing on what students are studying in History classes, such as the military dispatches found in The War of the Rebellion, the diplomatic messages collected in Foreign Relations of the United States, and the photographs taken by The Farms Security Administration in the 1930’s. The growing complexities of meaning in the texts I discuss make perfect sense from the perspective of developmental psychology. But so does my renewed interest in reading the stories that my grandchildren love. I suspect that every librarian could tell a similar story about their life-long love for books

    Supporting NGO Intermediation with Internet Systems: Comparing Mobile and Web Examples for Reaching Low Income Urban Youth of Cape Town

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    Intermediaries are necessary to overcome challenges of Internet use for many users in the developing world. However the need for co-presence with intermediaries can be inconvenient for beneficiaries, and the process is time consuming for intermediaries. We work with an NGO programme called Link which wanted to expose high school students from low income urban communities of Cape Town to Internet career guidance content, but did not have the staff power for regular in-person meetings with all of the students they wanted to reach. We present Internet-supported intermediation, in which intermediaries create a source of content that is tailored to beneficiaries and is accessible using the most appropriate Internet technologies for the context. We discuss the use of two technologies, the web as accessed by conventional computers (preferred by the NGO), and the mobile Internet accessed through low end feature phones. In the target demographic the mobile Internet is very popular for entertainment, especially because of low cost for communication via instant messaging, but the web is more frequently used for tasks outside of entertainment. Using an Action Research approach we implement two Internet systems to support Link intermediation, one a conventional website and the other a text interface suitable for access through mobile instant messaging. We evaluate the systems to determine whether they increase the impact of Link intermediation, and compare the usage of each to determine relative adoption of the technologies for a task outside of entertainment. Students demonstrated capable but slow website use in controlled evaluations, but almost no use occurred outside of our presence. Most students were experienced mobile Internet users, and some began unsolicited use of the mobile system and demonstrated it to their peers. In eight months of simultaneous deployment website users demonstrated minimal engagement, while mobile system users made repeated visits at all hours of the day from varied locations such as homes spread across the city. Students’ most frequent use of computers took place at venues where many users competed, and they prioritised other activities over the website during that access. Mobile use could take place when these restrictions did not apply. The mobile system demonstrated the benefit of Internet support for intermediation: the number of students who viewed career guidance content through it no longer affected the Link team’s effort, while students no longer had to travel to a single meeting place to access content. The consistent higher use of the mobile system than the website shows that the mobile Internet is suitable for non-entertainment use cases by low income urban youth

    ASP-based Discovery of Semi-Markovian Causal Models under Weaker Assumptions

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    In recent years the possibility of relaxing the so-called Faithfulness assumption in automated causal discovery has been investigated. The investigation showed (1) that the Faithfulness assumption can be weakened in various ways that in an important sense preserve its power, and (2) that weakening of Faithfulness may help to speed up methods based on Answer Set Programming. However, this line of work has so far only considered the discovery of causal models without latent variables. In this paper, we study weakenings of Faithfulness for constraint-based discovery of semi-Markovian causal models, which accommodate the possibility of latent variables, and show that both (1) and (2) remain the case in this more realistic setting

    The role of TcdB and TccC subunits in secretion of the photorhabdus Tcd toxin complex

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    The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5:1:1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man

    Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

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    Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

    ?2-Microglobulin Amyloid Fibril-Induced Membrane Disruption Is Enhanced by Endosomal Lipids and Acidic pH

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    Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of ?2-microglobulin (?2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of anionic lipid bilayers in vitro. However, the effect of lipid composition and the chemical environment in which ?2m-lipid interactions occur have not been investigated previously. Here we examine membrane damage resulting from the interaction of ?2m monomers and fibrils with lipid bilayers. Using dye release, tryptophan fluorescence quenching and fluorescence confocal microscopy assays we investigate the effect of anionic lipid composition and pH on the susceptibility of liposomes to fibril-induced membrane damage. We show that ?2m fibril-induced membrane disruption is modulated by anionic lipid composition and is enhanced by acidic pH. Most strikingly, the greatest degree of membrane disruption is observed for liposomes containing bis(monoacylglycero)phosphate (BMP) at acidic pH, conditions likely to reflect those encountered in the endocytic pathway. The results suggest that the interaction between ?2m fibrils and membranes of endosomal origin may play a role in the molecular mechanism of ?2m amyloid-associated osteoarticular tissue destruction in DRA

    Robotic-assisted transoral removal of a bilateral floor of mouth ranulas

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    <p>Abstract</p> <p>Objective</p> <p>To describe the management of bilateral oral ranulas with the use of the da Vinci Si Surgical System and discuss advantages and disadvantages over traditional transoral resection.</p> <p>Study Design</p> <p>Case Report and Review of Literature.</p> <p>Results</p> <p>A 47 year old woman presented to our service with an obvious right floor of mouth swelling. Clinical evaluation and computerized tomography scan confirmed a large floor of mouth ranula on the right and an incidental asymptomatic early ranula of the left sublingual gland. After obtaining an informed consent, the patient underwent a right transoral robotic-assisted transoral excision of the ranula and sublingual gland with identification and dissection of the submandibular duct and lingual nerve. The patient had an excellent outcome with no evidence of lingual nerve paresis and a return to oral intake on the first postoperative day. Subsequently, the patient underwent an elective transoral robotic-assisted excision of the incidental ranula on the left sublingual gland.</p> <p>Conclusion</p> <p>We describe the first robotic-assisted excision of bilateral oral ranulas in current literature. The use of the da Vinci system provides excellent visualization, magnification, and dexterity for transoral surgical management of ranulas with preservation of the lingual nerve and Wharton's duct with good functional outcomes. However, the use of the robotic system for anterior floor of mouth surgery in terms of improved surgical outcomes as compared to traditional transoral surgery, long-term recurrence rates, and cost effectiveness needs further validation.</p

    The Pseudomonas Quinolone Signal (PQS) Balances Life and Death in Pseudomonas aeruginosa Populations

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    When environmental conditions deteriorate and become inhospitable, generic survival strategies for populations of bacteria may be to enter a dormant state that slows down metabolism, to develop a general tolerance to hostile parameters that characterize the habitat, and to impose a regime to eliminate damaged members. Here, we provide evidence that the pseudomonas quinolone signal (PQS) mediates induction of all of these phenotypes. For individual cells, PQS, an interbacterial signaling molecule of Pseudomonas aeruginosa, has both deleterious and beneficial activities: on the one hand, it acts as a pro-oxidant and sensitizes the bacteria towards oxidative and other stresses and, on the other, it efficiently induces a protective anti-oxidative stress response. We propose that this dual function fragments populations into less and more stress tolerant members which respond differentially to developing stresses in deteriorating habitats. This suggests that a little poison may be generically beneficial to populations, in promoting survival of the fittest, and in contributing to bacterial multi-cellular behavior. It further identifies PQS as an essential mediator of the shaping of the population structure of Pseudomonas and of its response to and survival in hostile environmental conditions
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