202 research outputs found

    Soil Stabilization Manual 2014 Update

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    Soil Stabilization is used for a variety of activities including temporary wearing curses, working platforms, improving poor subgrade materials, upgrading marginal materials, dust control, and recycling old roads containing marginal materials. There are a number methods of stabilizing soils including modifying the gradation, the use of asphalt or cement stabilizers, geofiber stabilization and chemical stabilization. Selection of the method depends on the soil type, environment and application. This manual provide tools and guidance in the selection of the proper stabilization method and information on how to apply the method. A major portion of this manual is devoted to the use of stabilizing agents. The methods described here are considered best practices for Alaska.State of Alaska, Alaska Dept. of Transportation and Public Facilitie

    Manual for Thin Asphalt Overlays

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    This manual presents best practices on project selection, mix design, and construction to ensure a superior product when constructing thin asphalt overlays. Experience shows these treatments provide excellent performance when placed on pavements in fair to good condition using proper construction techniques. Though sometime referred to by other names, thin asphalt overlays have been widely used for pavement preservation throughout the world for over 50 years. Limited infrastructure funding at the local, state, and federal levels has resulted in greater emphasis on the use of pavement preservation techniques to extend pavement life and reduce maintenance costs. Thin asphalt overlays are one of many preventative maintenance treatments. Thin asphalt overlays are placed directly on existing pavement and can range from 1/2 inch to 1 1/2 inches in thickness. Thin asphalt overlays have proven to be an economical means for maintaining and improving the functional condition of an existing pavement since the 1960s. Specifically, this manual provides guidance for engineers regarding where and when to use thin asphalt overlays including: (1) Types and variations of thin overlays; (2) Materials and the design process; (3) Construction; (4) Quality Assurance; and (5) Troubleshooting. This chapter by chapter guidance enables an Agency’s engineers to design and construct a successful thin asphalt overlay project to completion. This manual is one of four new manuals prepared by the California Pavement Preservation Center (CP2Center) using funding from California Senate Bill 1 (SB-1), passed in April 2017. The other three manuals provide detailed design and construction information for (1) chip seals, (2) slurry surfacing, and (3) Cape seals. The creation of these manuals was a task funded entirely from SB-1 monies for the purpose of disseminating training and technical information on highway pavement preservation to local agencies throughout California

    Precision Measurement of the Weak Mixing Angle in Moller Scattering

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    We report on a precision measurement of the parity-violating asymmetry in fixed target electron-electron (Moller) scattering: A_PV = -131 +/- 14 (stat.) +/- 10 (syst.) parts per billion, leading to the determination of the weak mixing angle \sin^2\theta_W^eff = 0.2397 +/- 0.0010 (stat.) +/- 0.0008 (syst.), evaluated at Q^2 = 0.026 GeV^2. Combining this result with the measurements of \sin^2\theta_W^eff at the Z^0 pole, the running of the weak mixing angle is observed with over 6 sigma significance. The measurement sets constraints on new physics effects at the TeV scale.Comment: 4 pages, 2 postscript figues, submitted to Physical Review Letter

    Independent Prognostic Significance of Monosomy 17 and Impact of Karyotype Complexity in Monosomal Karyotype/Complex Karyotype Acute Myeloid Leukemia: Results from Four ECOG-ACRIN Prospective Therapeutic Trials

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    The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+ AML is not well defined. We analyzed data from 1,592 AML patients age 17–93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having β‰₯5 clonal abnormalities (CKβ‰₯ 5). MK+ patients with karyotype complexity ≀4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≀4 (p < 0.001), whereas no OS difference was seen in MK+ vs. MK- patients with CKβ‰₯ 5 (p = 0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p = 0.95). Monosomy 7 demonstrated no impact on OS in patients with CKβ‰₯ 5 (p = 0.39) or CK ≀ 4 (p = 0.44). Monosomy 17 appeared in 43% (68/158) of CKβ‰₯ 5 patients and demonstrated statistically significant worse OS (0.4y) compared to CKβ‰₯ 5 patients without monosomy 17 (0.5y; p = 0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML

    Synthesis and Investigation of a Radioiodinated F3 Peptide Analog as a SPECT Tumor Imaging Radioligand

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    A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[125I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [125I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C5 maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C2 maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [125I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [125I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [125I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques

    Increasing value and reducing waste in stroke research

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    Stroke represents a major burden to patients and society, and resources spent on stroke research must be used efficiently and produce good value in terms of improvements in human health. However, there are many examples of poor value from stroke research funding, which result from the way in which stroke research has been chosen, designed, conducted, analysed, regulated, managed, disseminated, or reported. In a project including a survey and a symposium and involving stroke researchers in the European Stroke Organisation we have sought to identify sources of inefficiency and waste, recommended approaches to increase value, and highlighted examples of best practice in stroke research. Recent evidence suggests that progress has been made, but there is room for much improvement, and stroke researchers, funders and other stakeholders might consider our recommendations when planning new research

    Loss of the Urothelial Differentiation Marker FOXA1 Is Associated with High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation

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    Approximately 50% of patients with muscle-invasive bladder cancer (MIBC) develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001), and loss of FOXA1 is associated with high histologic grade (p<0.001). Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC) exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes of MIBC and urothelial cell proliferation, and suggest an important role for FOXA1 in the malignant phenotype of MIBC

    The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

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    The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure
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