984 resultados para Northop, Philip M.
Resumo:
MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.
Resumo:
Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.
Resumo:
[book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.
Resumo:
Objective Australia has one of the highest skin cancer incidence and mortality rates in the world. Outdoor workers are a high risk group. Australian workplaces are undergoing large scale safety related changes, yet the mandate to provide specific sun safe practices remains absent. With much of the previous research aiming to improve sun safety in the workplace being quantitative in nature, relatively little is known about why certain sun safe strategies will or will not be successful in workplaces. Methods This qualitative article explores the enablers and barriers identified during an 18-month mixed methods project conducted in Queensland, Australia which aimed to improve workplace sun safe interventions. Results A variety of key enablers and barriers to implementing sun safe interventions in the workplace were identified, including presence of an engaged workplace champion, ownership and innovation by the workers. Conclusions These findings were part of a broader integration of interlinked qualitative and quantitative methods to yield a more complete picture of the determinants of the issue, implementation process and likelihood of changes at the workplace. Implications The paper provides guidance for public and occupational health practitioners on the selection of the most promising strategies when assisting workplaces to become sun safe.
Resumo:
A promotional brochure celebrating the completion of the Seagram Building in spring 1957 features on its cover intense portraits of seven men bisected by a single line of bold text that asks, “Who are these Men?” The answer appears on the next page: “They Dreamed of a Tower of Light” (Figures 1, 2). Each photograph is reproduced with the respective man’s name and project credit: architects, Mies van der Rohe and Philip Johnson; associate architect, Eli Jacques Kahn; electrical contractor, Harry F. Fischbach; lighting consultant, Richard Kelly; and electrical engineer, Clifton E. Smith. To the right, a rendering of the new Seagram Tower anchors the composition, standing luminous against a star-speckled night sky; its glass walls and bronze mullions are transformed into a gossamer skin that reveals the tower’s structural skeleton. Lightolier, the contract lighting manufacturer, produced the brochure to promote its role in the lighting of the Seagram Building, but Lightolier’s promotional copy was not far from the truth.
Resumo:
[Book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.
Resumo:
[Book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.
Resumo:
[Book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.
Resumo:
[Book] The potential of electric light as a new building “material” was recognized in the 1920s and became a useful design tool by the mid-century. Skillful lighting allowed for theatricality, narrative, and a new emphasis on structure and space. The Structure of Light tells the story of the career of Richard Kelly, the field’s most influential figure. Six historians, architects, and practitioners explore Kelly’s unparalleled influence on modern architecture and his lighting designs for some of the 20th century’s most iconic buildings: Philip Johnson’s Glass House; Louis Kahn’s Kimbell Art Museum; Eero Saarinen’s GM Technical Center; and Mies van der Rohe’s Seagram Building, among many others. This beautifully illustrated history demonstrates the range of applications, building types, and artistic solutions he employed to achieve a “nocturnal modernity” that would render buildings evocatively different at night. The survival of Kelly’s rich correspondence and extensive diaries allows an in-depth look at the triumphs and uncertainties of a young profession in the making. The first book to focus on the contributions of a master in the field of architectural lighting, this fascinating volume celebrates the practice’s significance in modern design.
Resumo:
We have studied the nonlinear optical properties of nanolayered Se/As2S3 film with a modulation period of 10 nm and a total thickness of 1.15 mu m at two [1064 nm (8 ns) and 800 nm (20 ps)] wavelengths using the standard Z-scan technique. Three-photon absorption was observed at off-resonant excitation and saturation of two-photon absorption at quasiresonant excitation. The observation of the saturation of two-photon absorption is because the pulse duration is shorter than the thermalization time of the photocreated carriers in their bands and three-photon absorption is due to high excitation irradiance. (c) 2007 American Institute of Physics.
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This paper investigates the association between board characteristics and the company’s corporate social responsibility (CSR) assurance decision in China. By examining 2054 firm-years of Chinese listed companies with CSR reports from 2008 to 2012, we find that firms with a large board size, more female directors, and separation of CEO and chairman positions are more likely to engage in CSR assurance. Gender diversity also influences the CSR assurance provider choice. However, board independence and overseas background of the CEO do not affect the CSR assurance decision. Inconsistent with our prediction, firms with foreign directors are less likely to engage in voluntary CSR assurance. In summary, this research provides in-depth insights into the determinants of Chinese firms’ voluntary CSR assurance.
Resumo:
The Australasian Society for Computers in Learning in Tertiary Education (ascilite) has recently completed research to inform development of the ALTC Exchange, a new online service for learning and teaching in Australia. The research investigated resource identification and contribution, engagement with the repository and user community, and associated peer review and commentary processes. This article focuses on the data obtained and recommendations developed for engagement of potential end users. It reports a literature review and findings, including an international perspective on the ALTC Exchange, with specific focus on prospective user needs, contexts of use and policies necessary to facilitate engagement of the higher education sector with the ALTC Exchange
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A discursive article examining the proposition that provisions for young people in care should be formally extended beyond their 18th birthday when care normally ends. Debate exists as to whether this should include a legislative extension to Care as has happened in some overseas jurisdictions or whether it is more appropriate to simply extend access to dedicated support provisions. The article concludes that both may have a place as long as the complexity of young people's situations is adequately responded to.
Resumo:
A diversity of programs oriented to young people seek to develop their capacities and their connection to the communities in which they live. Some focus on ameliorating a particular issue or ‘deficit’ whilst others, such as sporting, recreation and youth groups are more grounded in the community. This article reports a qualitative study undertaken in three remote Indigenous communities in Central Australia. Sixty interviews were conducted with a range of stakeholders involved in a diversity of youth programs. A range of critical challenges for and characteristics of remote Indigenous youth programs are identified if such programs are to be ‘fit for context’. ‘Youth centred-context specific’ provides a positive frame for the delivery of youth programs in remote Central Australia, encouraging an explicit focus on program logic; program content and processes; and relational, temporal, and, spatial aspects of the practice context. These provide lenses with which youth program planning and delivery may be enhanced in remote communities. Culturally safe service planning and delivery suggests locally determined processes for decision-making and community ownership. In some cases, this may mean a community preference for all ages to access the service to engage in culturally relevant activities. Where activities are targeted at young people, yet open to and inclusive of all ages, they provide a medium for cross-generational interaction that requires a high degree of flexibility on the part of staff and funding programs. Although the findings are focused in Central Australia, they may be relevant to similar contexts elsewhere.
Resumo:
While significant research has been undertaken exploring the pedagogical benefits of undertaking lengthy social work and human services field placements, there has been very little consideration regarding the potential financial stress involved for students. This study has addressed this knowledge gap. Research was conducted in 2014 using quantitative and qualitative methods with students, academic and professional staff from six Queensland Universities. The findings show a significant relationship between unpaid placements and financial hardship creating considerable stress for students and at times a compromised learning experience whilst on placement. The limited flexibility in the requirements of professional bodies and universities for how placements are undertaken has been identified as a key contributor to financial hardship. Addressing the complexities inherent in this issue requires a collaborative effort from multiple stakeholders and should not be regarded as a problem for students to endure and manage.