1,215 research outputs found

    A Framework for Guaranteed Maximum Price and Contingency Development for Integrated Delivery of Transportation Projects

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    This paper discusses the components of a guaranteed maximum price (GMP) and proposes a framework for the development of GMPs as contract payment provisions for construction manager-at-risk (CMR) and design-build (DB) contracts for transportation projects. The framework is the synthesis of a comprehensive literature review, a content analysis of CMR and DB solicitation documents and contracts, and case study project output from twelve projects in nine states worth $3.1 billion. The research also discusses the development of three common types of contingencies that are often utilized in projects with GMPs. The study concludes that owners should specify the structure of the GMP and its components to enhance clarity and understanding of the GMP’s composition. It recommends that this structure be included in the CMR and DB solicitation documents so that pricing proposals can be formulated in a manner that is consistent with the contract payment provisions that will be useful to practitioners that need to implement GMP-based contracts

    Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)

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    The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org

    A Multidimensional Model of Project Leadership

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    Critical Analysis of in situ Performance of Glass Fiber Core VIPs in Extreme Cold Climate

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    Glass fiber core vacuum insulation panels (VIPs) are becoming an increasingly attractive option for building envelope construction due to lower cost and availability around the world. Although fumed silica core VIPs have shown superior long-term performance under accelerated aging tests compared to glass fiber core VIPS, these laboratory test results have yet to be verified with long-term field performance data. In 2011, glass fiber core VIPs were installed in a commercial building retrofit project in Yukon, Canada (one of Canada's most northern territories), and have been continuously monitored since. This paper summarizes the thermal performance of the glass fiber core VIPs over the period of 2011–2018 in an extreme cold climate. Findings from this study provided data to validate glass fiber core VIP accelerated aging test results and the aging rate of VIPs in a cold and dry climate was determined. These results will help developing a better understanding of the long-term performance of glass fiber core VIPs in a real-world context

    Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

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    E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

    Competing biosecurity and risk rationalities in the Chittagong poultry commodity chain, Bangladesh

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    This paper anthropologically explores how key actors in the Chittagong live bird trading network perceive biosecurity and risk in relation to avian influenza between production sites, market maker scenes and outlets. They pay attention to the past and the present, rather than the future, downplaying the need for strict risk management, as outbreaks have not been reported frequently for a number of years. This is analysed as ‘temporalities of risk perception regarding biosecurity’, through Black Swan theory, the idea that unexpected events with major effects are often inappropriately rationalized (Taleb in The Black Swan. The impact of the highly improbable, Random House, New York, 2007). This incorporates a sociocultural perspective on risk, emphasizing the contexts in which risk is understood, lived, embodied and experienced. Their risk calculation is explained in terms of social consent, practical intelligibility and convergence of constraints and motivation. The pragmatic and practical orientation towards risk stands in contrast to how risk is calculated in the avian influenza preparedness paradigm. It is argued that disease risk on the ground has become a normalized part of everyday business, as implied in Black Swan theory. Risk which is calculated retrospectively is unlikely to encourage investment in biosecurity and, thereby, points to the danger of unpredictable outlier events

    The Angular Correlation Function of Galaxies from Early SDSS Data

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    The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local Universe. In this Letter we present some of the initial results on the angular 2-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18<r*<22, is shown to be consistent with results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1 arcminute and 1 degree the correlation function is well described by a power-law with an exponent of ~ -0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analyses from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1-2 degrees. On small scales, < 1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'< theta <0.5 deg data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high precision measurements of the power-law angular correlation function on angular scales 1' < theta < 1 deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small and large scale regimes, measurements of higher-order correlations, and studies of angular clustering as a function of redshift and galaxy type

    Epidemiology, prehospital care and outcomes of patients arriving by ambulance with dyspnoea: An observational study

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    Background: This study aimed to determine epidemiology and outcome for patients presenting to emergency departments (ED) with shortness of breath who were transported by ambulance. Methods: This was a planned sub-study of a prospective, interrupted time series cohort study conducted at three time points in 2014 and which included consecutive adult patients presenting to the ED with dyspnoea as a main symptom. For this sub-study, additional inclusion criteria were presentation to an ED in Australia or New Zealand and transport by ambulance. The primary outcomes of interest are the epidemiology and outcome of these patients. Analysis was by descriptive statistics and comparisons of proportions. Results: One thousand seven patients met inclusion criteria. Median age was 74 years (IQR 61-68) and 46.1 % were male. There was a high rate of co-morbidity and chronic medication use. The most common ED diagnoses were lower respiratory tract infection (including pneumonia, 22.7 %), cardiac failure (20.5%) and exacerbation of chronic obstructive pulmonary disease (19.7 %). ED disposition was hospital admission (including ICU) for 76.4 %, ICU admission for 5.6 % and death in ED in 0.9 %. Overall in-hospital mortality among admitted patients was 6.5 %. Discussion: Patients transported by ambulance with shortness of breath make up a significant proportion of ambulance caseload and have high comorbidity and high hospital admission rate. In this study, >60 % were accounted for by patients with heart failure, lower respiratory tract infection or COPD, but there were a wide range of diagnoses. This has implications for service planning, models of care and paramedic training. Conclusion: This study shows that patients transported to hospital by ambulance with shortness of breath are a complex and seriously ill group with a broad range of diagnoses. Understanding the characteristics of these patients, the range of diagnoses and their outcome can help inform training and planning of services

    BST2/Tetherin Enhances Entry of Human Cytomegalovirus

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    Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV

    Multi-wavelength lens construction of a Planck and Herschel-detected star-bursting galaxy

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    We present a source-plane reconstruction of a Herschel and Planck-detected gravitationally lensed dusty star-forming galaxy (DSFG) at z = 1.68 using Hubble, Submillimeter Array (SMA), and Keck observations. The background submillimeter galaxy (SMG) is strongly lensed by a foreground galaxy cluster at z = 0.997 and appears as an arc with a length of ∼15″ in the optical images. The continuum dust emission, as seen by SMA, is limited to a single knot within this arc. We present a lens model with source-plane reconstructions at several wavelengths to show the difference in magnification between the stars and dust, and highlight the importance of multi-wavelength lens models for studies involving lensed DSFGs. We estimate the physical properties of the galaxy by fitting the flux densities to model spectral energy distributions leading to a magnification-corrected starformation rate (SFR) of 390 ± 60 M yr−1 and a stellar mass of 1.1 ± 0.4 10 x 11 M. These values are consistent with high-redshift massive galaxies that have formed most of their stars already. The estimated gas-to-baryon fraction, molecular gas surface density, and SFR surface density have values of 0.43 ± 0.13, 350 ± 200 M pc−2, and ~ 12 7 M yr−1 kpc−2, respectively. The ratio of SFR surface density to molecular gas surface density puts this among the most star-forming systems, similar to other measured SMGs and local ULIRGs
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