Investigation into the variations of moisture content of two buildings constructed with light earth walls

This paper briefly describes the background to light earth buildings and details a series of moisture measurements undertaken upon the clay and straw, (light earth) constructed walls of two UK based buildings. The methodology of measurement that was based upon previous studies undertaken on walls made from straw bales is described. A novel ‘in-wall’ wet heating system used in one of the two buildings allows the investigation of the effects of direct wall heating upon the distribution of moisture in the walls. The influence of exterior and interior temperature and humidity are described as are the variations in moisture migration introduced by the in-wall heating system. It was concluded that both buildings have exterior wall moisture content readings that indicate little risk of degradation due to interior wall moisture levels (although the Studio walls do exhibit higher and if suffered over long time periods, dangerous moisture readings for part of the measurement period)

Immunomodulation in Osteosarcoma: From Therapy to Diagnostics

Osteosarcoma (OS) is a rare pediatric bone malignancy. Those who develop advanced disease, often in the form of metastasis to the lung, experience poor five-year survival rates near approximately 25%. Considering minimal-to-no therapeutic breakthroughs have occurred for treatment of this disease since the 1980s, efforts to develop new therapeutics are underway. The goal of this dissertation was to initiate the preclinical efforts necessary to reinvigorate the use of immunostimulatory cytokine therapy for the treatment of OS and other solid tumors. This effort would not only include the development of the immunotherapeutic known as IL12ns, but also the clinical diagnostic tools that would be necessary for safe and efficacious use of this therapy in future clinical practice. This work first details the extensive efforts made to develop IL-12-loaded poly (lactic-co-glycolic acid) (PLGA) nanospheres, IL12ns, hypothesized to limit the previous side effects and immunotoxicity observed in human clinical trials of bolus IL-12 therapy through the improved pharmacodynamics of a vector delivery platform. Through use of the double-emulsion solvent evaporation (DESE) method with homogenization, we successfully encapsulated and delivered IL12ns in a murine model, achieving systemic delivery to peripheral tissues while generating desirable peripheral immune responses associated with IL-12 therapeutic efficacy. Next, to improve the likelihood of future commercialization of IL12ns, extensive efforts were made to increase both encapsulation efficiency and fabrication yield by using both synthesis modifiers (surfactants and carrier proteins) and ultrasonication. An optimized IL12ns was then examined in a preclinical model of murine metastatic OS, exhibiting preliminary therapeutic efficacy. Furthermore, efforts to shift the treatment paradigm of OS toward the use of immunostimulatory therapies will likely necessitate the concomitant development of immune diagnostic platforms capable of monitoring disease progression and therapeutic response. Clinical tools to stratify patients by likely responder status before the initiation of alternative therapies will help best optimize patient care in a future data-oriented clinical practice driven by patient-specific immunological insights. To do so, we initiated the development of an immune diagnostic platform capable of assessing changes in the systemic immune proteome and transcriptome with IL12ns therapy through repeated blood sampling. Markers of beneficial and maladaptive immune responses to IL-12 therapy, measured by the platform, will be critical assessments utilized in future human clinical trials to prevent overt clinical toxicity while best modulating the delivery of this therapy. Additionally, both a retrospective analysis of common clinical laboratory measures (such as a complete blood count) and spatial multiplexed immunofluorescence analysis of tumor specimens revealed peripheral and local immunological patterns associated with sarcoma disease that could help identify candidates for alternative immunotherapies, as opposed to the current standard of care. Finally, through efforts to characterize the systemic proteomic profile of OS patients, apo-transcobalamin-II (APO-TCN2) was identified as a novel biomarker of overall survival in this disease. Considering its likely role in the lymphoproliferation of B and plasma cells, this circulatory protein should be considered a novel immunotherapy candidate that necessitates further preclinical examination. Ultimately, these data lay the foundation for the future of OS treatment including the deployment of alternative immunotherapeutic strategies alongside data-driven diagnostic platforms that convey patient-specific immunological insights for optimal clinical decision making, robust therapeutic responses, and better patient outcomes

Automated, Reliable, and Efficient Continental-Scale Replication of 7.3 Petabytes of Climate Simulation Data: A Case Study

We report on our experiences replicating 7.3 petabytes (PB) of Earth System Grid Federation (ESGF) climate simulation data from Lawrence Livermore National Laboratory (LLNL) in California to Argonne National Laboratory (ANL) in Illinois and Oak Ridge National Laboratory (ORNL) in Tennessee. This movement of some 29 million files, twice, undertaken in order to establish new ESGF nodes at ANL and ORNL, was performed largely automatically by a simple replication tool, a script that invoked Globus to transfer large bundles of files while tracking progress in a database. Under the covers, Globus organized transfers to make efficient use of the high-speed Energy Sciences network (ESnet) and the data transfer nodes deployed at participating sites, and also addressed security, integrity checking, and recovery from a variety of transient failures. This success demonstrates the considerable benefits that can accrue from the adoption of performant data replication infrastructure

Proteomic and transcriptomic analyses identify apo-transcobalamin-II as a biomarker of overall survival in osteosarcoma

BackgroundThe large-scale proteomic platform known as the SomaScan® assay is capable of simultaneously measuring thousands of proteins in patient specimens through next-generation aptamer-based multiplexed technology. While previous studies have utilized patient peripheral blood to suggest serum biomarkers of prognostic or diagnostic value in osteosarcoma (OSA), the most common primary pediatric bone cancer, they have ultimately been limited in the robustness of their analyses. We propose utilizing this aptamer-based technology to describe the systemic proteomic milieu in patients diagnosed with this disease.MethodsTo determine novel biomarkers associated with overall survival in OSA, we deployed the SomaLogic SomaScan® 7k assay to investigate the plasma proteomic profile of naive primary, recurrent, and metastatic OSA patients. Following identification of differentially expressed proteins (DEPs) between 2-year deceased and survivor cohorts, publicly available databases including Survival Genie, TIGER, and KM Plotter Immunotherapy, among others, were utilized to investigate the significance of our proteomic findings.ResultsApo-transcobalamin-II (APO-TCN2) was identified as the most DEP between 2-year deceased and survivor cohorts (Log2 fold change = 6.8, P-value = 0.0017). Survival analysis using the Survival Genie web-based platform indicated that increased intratumoral TCN2 expression was associated with better overall survival in both OSA (TARGET-OS) and sarcoma (TCGA-SARC) datasets. Cell-cell communication analysis using the TIGER database suggested that TCN2+ Myeloid cells likely interact with marginal zone and immunoglobin-producing B lymphocytes expressing the TCN2 receptor (CD320) to promote their proliferation and survival in both non-small cell lung cancer and melanoma tumors. Analysis of publicly available OSA scRNA-sequencing datasets identified similar populations in naive primary tumors. Furthermore, circulating APO-TCN2 levels in OSA were then associated with a plasma proteomic profile likely necessary for robust B lymphocyte proliferation, infiltration, and formation of intratumoral tertiary lymphoid structures for improved anti-tumor immunity.ConclusionsOverall, APO-TCN2, a circulatory protein previously described in various lymphoproliferative disorders, was associated with 2-year survival status in patients diagnosed with OSA. The relevance of this protein and apparent immunological function (anti-tumor B lymphocyte responses) was suggested using publicly available solid tumor RNA-sequencing datasets. Further studies characterizing the biological function of APO-TCN2 and its relevance in these diseases is warranted

Experiences Building Globus Genomics: A Next-Generation Sequencing Analysis Service using Galaxy, Globus, and Amazon Web Services

ABSTRACT We describe Globus Genomics, a system that we have developed for rapid analysis of large quantities of next-generation sequencing (NGS) genomic data. This system achieves a high degree of end-to-end automation that encompasses every stage of data analysis including initial data retrieval from remote sequencing centers or storage (via the Globus file transfer system); specification, configuration, and reuse of multi-step processing pipelines (via the Galaxy workflow system); creation of custom Amazon Machine Images and on-demand resource acquisition via a specialized elastic provisioner (on Amazon EC2); and efficient scheduling of these pipelines over many processors (via the HTCondor scheduler). The system allows biomedical researchers to perform rapid analysis of large NGS datasets in a fully automated manner, without software installation or a need for any local computing infrastructure. We report performance and cost results for some representative workloads

Preparing Low-Income Middle and Secondary Students to Participate Effectively in Academic Discourse Through Writing

Students from low-income families often perform poorly on formal assessments in language arts. Examining data using the 2008-2009 State of New Jersey Department of Education School Report Cards, a comparison was made between low-income districts and affluent districts in three areas: High School Proficiency Assessment Language Arts Literacy Scores, SAT Verbal Scores and SAT Essay Scores. Students from low-income districts performed significantly lower in these areas than students from the higher income districts and from the average performance rates for the State of New Jersey. This lag in performance affects students’ choices for higher education, for job opportunities, as well as their abilities to communicate in writing, which is necessary in daily life. Factors that impact this disparity in achievement include that students may not speak Standard English either because they or their parents are from another country or because few, if any, in the family have had formal education, which also affects vocabulary development. There may be a lack of resources available to them at home such as print material, technology and enrichment opportunities. The type and quality of writing instruction students receive and the demands and expectations that are presented to them by the schools they attend may not reflect high standards or rigor. Indicators of this include large class sizes and students being placed in lower track classes where the content of instruction may be less than in other settings. To address the needs of underprepared students, a comprehensive review was made of the available research on writing instruction to determine effective teaching methods that can help improve the skills of low-income middle and secondary students. An analysis of strategies was undertaken to find those practices that should be incorporated into a program of writing instruction. From my experience and from the research I reviewed, if middle and secondary students who are from low-income backgrounds are to be prepared to participate effectively in academic discourse through writing, they need to be exposed to writing instruction that takes into account their backgrounds, skill levels and social and emotional needs. Authentic writing assignments from which students can understand their purpose help to develop students’ competencies, as does the critical thinking needed in learning to present cohesive arguments. Direct instruction in writing helps build proficiency, along with the writing process when it is explicitly taught in steps. Teacher questioning and feedback are among the most powerful ways to improve student writing but these are skills that must be developed. The practices that should be incorporated into an effective program of writing instruction according to Delpit, Hull, Tompkins and others include designing quality assignments which offer students meaningful ways to practice discourse, making instruction explicit through teaching skills, not in isolation, but as part of purposeful writing, providing comprehensive feedback on students’ writing which goes beyond surface errors to address structure and content and ongoing professional development for teachers in best practices in writing instruction. Finally, teachers must be aware of their attitudes toward the students they teach, realizing that poor grammar, lack of spelling skills or use of Non-standard English do not mean that students are lacking in intelligence or do not have valuable things to say. Therefore, a writing program that offers explicit instruction in conjunction with process writing, has assignments grounded in purpose and meaning as its foundation, aids teachers with professional development and recognizes the innate abilities of the novice writers would provide low-income students with the educational experiences necessary to advance their performance with academic discourse

ASYMPTOTIC MODELS OF THE HEAT TRANSFER IN LAMINATED CONDUCTORS

International audienceLaminated materials play an important role in civil engineering. The contribution is focused on the modelling of heat conduction in these materials. The analysis is carried out in the framework of the tolerance averaging technique, [1]. A new asymptotic procedure for finding solutions to the specific heat conduction problems is proposed. General results are illustrated by some numerical examples and compared with those derived from homogenization technique, [2]

The Defense Department and innovation : an assessment of the technical and policy challenges of airborne boost-phase intercept

Thesis: S.M. in Technology and Policy, Massachusetts Institute of Technology, School of Engineering, Institute for Data, Systems, and Society, Technology and Policy Program, 2017.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 97-102).Technological innovation broadly is one of the major sources societal advance. In the realm of defense, it is of prime importance to the strategic interests of a nation. Defense innovation policy is the culmination of a variety of factors, including considerations of the future strategic environment, bureaucratic and organizational politics between military services and civilian agencies, and domestic politics. The differing degrees of influence of these inputs often helps to explain the resultant systems. A case study of particular interest in United States' defense innovation is the modern evolution of missile defense systems. Such evolution principally began under the Reagan administration in response to the threat from the Soviet Union and continues today to meet emerging missile threats. With the emergence of the North Korean ballistic missile threat, a new capability using unmanned aerial vehicles to intercept missiles during boost phase may increase capability to defend the United States from missile attack. To assess why such a system does not currently exist, the viability of such a system, and understand how to field such a system, the following framework is developed: 1. A historical analysis of the origins of current missile defense systems and the implications of its legacy; 2. The establishment of a policy consensus of a shift in missile defense towards North Korea and the identification of a technological opportunity in boost-phase intercept; 3. Building a political coalition to support the new boost-phase intercept system; 4. Case studies on previous missile defense efforts to develop a good product. This thesis identifies concurrency in acquisitions to provide rapid capability against emerging third-world missile threats as a prime reason for the lack of a current boost-phase intercept capability. Next, it shows that a system based on the MQ-9 Reaper could provide the capability to intercept notional intercontinental- and intermediate-range ballistic missiles from representative geographies in the near-term. Finally, it suggests a political coalition incorporating the combatant commands and the United States Navy due to operational and organizational interests to champion the development of such a system, incorporating recommendations to improve the acquisitions process.by Samuel S. Lacinski.S.M. in Technology and Polic