797 research outputs found

    ‘Capital’ City: Creating an Approach to Urban Development in a Monumental City

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    Washington DC is the political capital of the country, nestled within a working city. It is under international scrutiny everyday, acting as the face we show the world. A recent development in the center city showed the world our view on future urban development, as the historic Chinatown was completely demolished to make way for new condos and a convention center, leaving a single street for nostalgia. Is this how we should think about our cities futures? As architects, we often become obsessed with the details of our designs, forgetting the larger forces that impact these projects, or that they may have on the areas around them. Instead of being a part of a united system, they act as islands in a sea of infill, separate from the daily life of the people around them. This form of design is unacceptable. Design needs to be approached simultaneously from several different lenses in order to have a positive impact on its environment. Starting with the formation of Washington DC, the first planned city in the United States, I began to study the different forces that impact the development of a urban center. Washington DC is the result of two antagonistic forces pushing against each other in the form of private economic development and symbolic design. I contended that the best way to approach future development in the city, was to use both these forms of design together, creating a plan that was both financially viable and symbolically significant. To test this, I decided to look at an area in the Southeast of the District. Anacostia and Buena Vista are a larger neighborhood on the brink of development. Most current proposals are either too small to aid the area [ bringing some district offices ] or too insensitive to the current population [ the gentrification of a historically black and low income region ]. My particular site in the area is a large block of land which contains the existing metro station for the neighborhoods, as well as acting as a transportation hub for the Southeast. However, due to political issues, it was built a distance away from the actual neighborhood center. I chose to give look at this area, and gave the community something it lacks and needs no matter what income of people reside there, while also promoting both tourism and economic growth. A public market. It would act as both an attractor to the area, but would also act to feed and employ the current population in a place already easily accessible by metro and bus. It makes the area a destination, as well as a integral part of the daily life of its citizens. But while adding a market may solve the food desert issue facing the region, a single building, no matter how large it may be, cannot solve the issues of an area. Real and lasting change has to happen on all scales of development. To begin to think as a urban designer, I had to first understand the profession and its role in rethinking urban development. Then, using the knowledge gathered through research, I was able to finally think of how an urban designer would begin to approach the neighborhood beyond my particular site. This allowed me to consider how my project would act as just a small piece in a larger project to connect the surrounding areas to the rest of the city with the additions of civic structures, retail, and open space. Yet most importantly, the neighborhoods would still retain the very thing that makes them unique, their character. The end goal was to look at design from all different scales and lenses in order to create an approach to future urban development as cities continue to grow. And with this project, I believe I have created a viable answer

    Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia

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    Few studies have compared gene expression in paediatric and adult acute myeloid leukaemia (AML). In this study, we have analysed mRNA-sequencing data from two publicly accessible databases: (1) National Cancer Institute's Therapeutically Applicable Research to Generate Effective Treatments (NCI-TARGET), examining paediatric patients, and (2) The Cancer Genome Atlas (TCGA), examining adult patients with AML. With a particular focus on 144 known tumour antigens, we identified STEAP1, SAGE1, MORC4, SLC34A2 and CEACAM3 as significantly different in their expression between standard and low risk paediatric AML patient subgroups, as well as between poor and good, and intermediate and good risk adult AML patient subgroups. We found significant differences in event-free survival (EFS) in paediatric AML patients, when comparing standard and low risk subgroups, and quartile expression levels of BIRC5, MAGEF1, MELTF, STEAP1 and VGLL4. We found significant differences in EFS in adult AML patients when comparing intermediate and good, and poor and good risk adult AML patient subgroups and quartile expression levels of MORC4 and SAGE1, respectively. When examining Kyoto Encyclopedia of Genes and Genomes (KEGG) (2016) pathway data, we found that genes altered in AML were involved in key processes such as the evasion of apoptosis (BIRC5, WNT1) or the control of cell proliferation (SSX2IP, AML1-ETO). For the first time we have compared gene expression in paediatric AML patients with that of adult AML patients. This study provides unique insights into the differences and similarities in the gene expression that underlies AML, the genes that are significantly differently expressed between risk subgroups, and provides new insights into the molecular pathways involved in AML pathogenesis

    The structure of calomel, Hg2C12, derived from neutron powder data

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    Powder structure / Mercur

    The structure of calomel, Hg2C12, derived from neutron powder data

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    Powder structure / Mercur

    Capacity to Elicit Cytotoxic CD8 T Cell Activity Against Mycobacterium avium subsp. paratuberculosis Is Retained in a Vaccine Candidate 35 kDa Peptide Modified for Expression in Mammalian Cells

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    Studies focused on development of an attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of paratuberculosis (Ptb) in cattle and other species, revealed that deletion of relA, a global gene regulator, abrogates the ability of Map to establish a persistent infection. In the absence of relA, cattle develop CD8 cytotoxic T cells (CTL) with the ability to kill intracellular bacteria. Analysis of the recall response to a relA mutant, Map/relA, with cells from a vaccinated steer demonstrated that a 35-kDa membrane peptide (MMP) is one of the targets of the response. This observation suggested that it might be possible to develop a peptide-based vaccine. As reported here, the gene encoding the hypothetical MMP ORF, MAP2121c, was modified for expression in mammalian cells as a first step in developing an expression cassette for incorporation into a mammalian expression vector. The modified sequence of MMP, tPA-MMP, was mutated to generate two additional sequences for the study, one with substitutions to replace five potential residues that could be glycosylated, tPA-MMP-5mut, and one with substitutions to replace the first two potential residues that could be glycosylated, tPA-MMP-2mut. The sequences were placed in an expression cassette to produce peptides for analysis. An ex vivo platform was used with flow cytometry and a bacterium viability assay to determine if modifications in the gene encoding MMP for expression in mammalian cells altered its capacity to elicit development of CD8 CTL, essential for its use in a peptide-based vaccine. Monocyte-depleted PBMC (mdPBMC) were stimulated with antigen-presenting cells (APC) pulsed with different MMP constructs. CD4 and CD8 T cells proliferated in response to stimulation with MMP (control) expressed in Escherichia coli (eMMP), tPA-MMP, and tPA-MMP-2mut. CD8 T cells retained the capacity to kill intracellular bacteria. The tPA-MMP-5mut failed to elicit a proliferative response and was not included in further studies. The data show that the expression cassettes containing MMP and MMP-2mut can be used to screen and select a mammalian expression vector for the development of an efficacious peptide-based vaccine against Ptb

    Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group

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    PURPOSE: To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. PATIENTS AND METHODS: Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. RESULTS: Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). CONCLUSION: Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults

    Comparing composite likelihood methods based on pairs for spatial Gaussian random fields

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    In the last years there has been a growing interest in proposing methods for estimating covariance functions for geostatistical data. Among these, maximum likelihood estimators have nice features when we deal with a Gaussian model. However maximum likelihood becomes impractical when the number of observations is very large. In this work we review some solutions and we contrast them in terms of loss of statistical efficiency and computational burden. Specifically we focus on three types of weighted composite likelihood functions based on pairs and we compare them with the method of covariance tapering. Asymptotic properties of the three estimation methods are derived. We illustrate the effectiveness of the methods through theoretical examples, simulation experiments and by analyzing a data set on yearly total precipitation anomalies at weather stations in the United States.In the last years there has been a growing interest in proposing methods for estimating covariance functions for geostatistical data. Among these, maximum likelihood estimators have nice features when we deal with a Gaussian model. However maximum likelihood becomes impractical when the number of observations is very large. In this work we review some solutions and we contrast them in terms of loss of statistical efficiency and computational burden. Specifically we focus on three types of weighted composite likelihood functions based on pairs and we compare them with the method of covariance tapering. Asymptotic properties of the three estimation methods are derived. We illustrate the effectiveness of the methods through theoretical examples, simulation experiments and by analyzing a data set on yearly total precipitation anomalies at weather stations in the United States

    Capacity to Elicit Cytotoxic CD8 T Cell Activity Against Mycobacterium avium subsp. paratuberculosis Is Retained in a Vaccine Candidate 35 kDa Peptide Modified for Expression in Mammalian Cells

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    Studies focused on development of an attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of paratuberculosis (Ptb) in cattle and other species, revealed that deletion of relA, a global gene regulator, abrogates the ability of Map to establish a persistent infection. In the absence of relA, cattle develop CD8 cytotoxic T cells (CTL) with the ability to kill intracellular bacteria. Analysis of the recall response to a relA mutant, Map/relA, with cells from a vaccinated steer demonstrated that a 35-kDa membrane peptide (MMP) is one of the targets of the response. This observation suggested that it might be possible to develop a peptide-based vaccine. As reported here, the gene encoding the hypothetical MMP ORF, MAP2121c, was modified for expression in mammalian cells as a first step in developing an expression cassette for incorporation into a mammalian expression vector. The modified sequence of MMP, tPA-MMP, was mutated to generate two additional sequences for the study, one with substitutions to replace five potential residues that could be glycosylated, tPA-MMP-5mut, and one with substitutions to replace the first two potential residues that could be glycosylated, tPA-MMP-2mut. The sequences were placed in an expression cassette to produce peptides for analysis. An ex vivo platform was used with flow cytometry and a bacterium viability assay to determine if modifications in the gene encoding MMP for expression in mammalian cells altered its capacity to elicit development of CD8 CTL, essential for its use in a peptide-based vaccine. Monocyte-depleted PBMC (mdPBMC) were stimulated with antigen-presenting cells (APC) pulsed with different MMP constructs. CD4 and CD8 T cells proliferated in response to stimulation with MMP (control) expressed in Escherichia coli (eMMP), tPA-MMP, and tPA-MMP-2mut. CD8 T cells retained the capacity to kill intracellular bacteria. The tPA-MMP-5mut failed to elicit a proliferative response and was not included in further studies. The data show that the expression cassettes containing MMP and MMP-2mut can be used to screen and select a mammalian expression vector for the development of an efficacious peptide-based vaccine against Ptb

    Investigation of the Chaotic Dynamics of an Electron Beam with a Virtual Cathode in an External Magnetic Field

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    The effect of the strength of the focusing magnetic field on chaotic dynamic processes occurring inan electron beam with a virtual cathode, as well as on the processes whereby the structures form in the beamand interact with each other, is studied by means of two-dimensional numerical simulations based on solving a self-consistent set of Vlasov-Maxwell equations. It is shown that, as the focusing magnetic field is decreased,the dynamics of an electron beam with a virtual cathode becomes more complicated due to the formation andinteraction of spatio-temporal longitudinal and transverse structures in the interaction region of a vircator. The optimum efficiency of the interaction of an electron beam with the electromagnetic field of the vircator isachieved at a comparatively weak external magnetic field and is determined by the fundamentally two-dimensional nature of the motion of the beam electrons near the virtual cathode.Comment: 12 pages, 8 figure

    Simulation of dimensionality effects in thermal transport

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    The discovery of nanostructures and the development of growth and fabrication techniques of one- and two-dimensional materials provide the possibility to probe experimentally heat transport in low-dimensional systems. Nevertheless measuring the thermal conductivity of these systems is extremely challenging and subject to large uncertainties, thus hindering the chance for a direct comparison between experiments and statistical physics models. Atomistic simulations of realistic nanostructures provide the ideal bridge between abstract models and experiments. After briefly introducing the state of the art of heat transport measurement in nanostructures, and numerical techniques to simulate realistic systems at atomistic level, we review the contribution of lattice dynamics and molecular dynamics simulation to understanding nanoscale thermal transport in systems with reduced dimensionality. We focus on the effect of dimensionality in determining the phononic properties of carbon and semiconducting nanostructures, specifically considering the cases of carbon nanotubes, graphene and of silicon nanowires and ultra-thin membranes, underlying analogies and differences with abstract lattice models.Comment: 30 pages, 21 figures. Review paper, to appear in the Springer Lecture Notes in Physics volume "Thermal transport in low dimensions: from statistical physics to nanoscale heat transfer" (S. Lepri ed.
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