Design from Recycling

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Functional analysis of P53 negative regulators in Bombyx mori

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Long-Term Pavement Performance Indicators for Failed Materials

State Transportation Agencies (STAs) use quality control/quality assurance (QC/QA) specifications to guide the testing and inspection of road pavement construction. Although failed materials of pavement rarely occur in practice, it is critical to have a sound decision framework to assist in making data-driven, informed decisions regarding failed materials because such decisions have profound impacts on the long-term performance of the pavement and the operation and maintenance costs of the responsible highway agencies. A performance-related specification (PRS) is a quality acceptance (QA) specification that specifies the acceptable levels of key acceptance quality characteristics (AQCs) that are directly related to fundamental engineering properties, which in turn, determine the long-term performance of the constructed end products. Two PRS tools, PaveSpec for Portland Cement Concrete Pavement (PCCP) and Quality Related Specification Software (QRSS) for QC/QA Hot Mixed Asphalt (HMA) pavement, were investigated in this study to develop decision frameworks for PCCP and HMA pavement to assist the decision-making regarding failed materials at INDOT. A large number of simulations of various scenarios in the context of INDOT pavement construction were conducted to fully develop and implement the decision framework. For PCCP, the newly developed decision framework based on PaveSpec was validated using data from an INDOT construction project. The framework is readily implementable to assist INDOT in making informed decision regarding failed materials for PCCP. For QC/QA pavement, it was found that QRSS is not an appropriate PRS tool to estimate the long-term performance because of its limitations, the misalignment between QRSS process and INDOT practice, and erroneous simulation results

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.National Institutes of Health (U.S.) (Grant P01 CA066996)National Institutes of Health (U.S.) (Grant R01 HL082945)National Cancer Institute (U.S.) (Grant P30-CA14051

Trisomy of a Down Syndrome Critical Region Globally Amplifies Transcription via HMGN1 Overexpression

Down syndrome (DS, trisomy 21) is associated with developmental abnormalities and increased leukemia risk. To reconcile chromatin alterations with transcriptome changes, we performed paired exogenous spike-in normalized RNA and chromatin immunoprecipitation sequencing in DS models. Absolute normalization unmasks global amplification of gene expression associated with trisomy 21. Overexpression of the nucleosome binding protein HMGN1 (encoded on chr21q22) recapitulates transcriptional changes seen with triplication of a Down syndrome critical region on distal chromosome 21, and HMGN1 is necessary for B cell phenotypes in DS models. Absolute exogenous-normalized chromatin immunoprecipitation sequencing (ChIP-Rx) also reveals a global increase in histone H3K27 acetylation caused by HMGN1. Transcriptional amplification downstream of HMGN1 is enriched for stage-specific programs of B cells and B cell acute lymphoblastic leukemia, dependent on the developmental cellular context. These data offer a mechanistic explanation for DS transcriptional patterns and suggest that further study of HMGN1 and RNA amplification in diverse DS phenotypes is warranted. How trisomy 21 contributes to Down syndrome phenotypes, including increased leukemia risk, is not well understood. Mowery et al. use per-cell normalization approaches to reveal global transcriptional amplification in Down syndrome models. HMGN1 overexpression is sufficient to induce these alterations and promotes lineage-associated transcriptional programs, signaling, and B cell progenitor phenotypes

Pavement Acceptance Testing: Risk-Controlled Sampling Strategy

Acceptance testing is a critical aspect of the quality control and quality assurance (QC/QA) program to ensure the reliable long-term performance of pavement. A typical acceptance testing specification includes acceptable quality characteristics (AQCs), testing methods, number of samples, sample locations, and acceptance criteria. In the current practice, Indiana Department of Transportation (INDOT) accepts pavement by sampling and testing materials with a pre-determined, very low frequency at random locations, leading to a significant problem: testing results are not truly “representative” of the project because sampling is neither based on a statistical foundation, nor on the reliability concept. This study developed a systematic guideline that has addressed the aforementioned problem of material acceptance testing in four aspects: identifying key material properties for testing, selecting sample locations, designing acceptance criteria, and determining optimal sample size. Key material properties that are critical to the pavement long-term performance are identified by comparing with sensitive material properties in MEPDG. A random sampling mechanism was devised based on two spatial indices to control the spatial pattern of samples to minimize the influence from spatial autocorrelation. Risk-based acceptance criteria was proposed based on statistical methods to control the agency’s risk at a desired level given a specific sampling and testing strategy, based on which optimal sample size is determined from a risk perspective. Cost analysis approaches were developed to estimate the total cost of acceptance testing by integrating the risk of making incorrect decision and enable the determination of optimal sample size from a cost perspective. Additionally, quality control chart was exploited as a complementary tool to ensure the consistency of the pavement quality of a project. The results of this study were validated using real data from INDOT projects, and a web tool that incorporates the newly created methods in this study was developed to assist the field pavement QA practice

Intelligent Compaction of Soils—Data Interpretation and Role in QC/QA Specifications

This report describes a study of intelligent compaction (IC) technologies, within the context of actual construction projects, for its potential as a component of INDOT’s QC/QA for soils. The output from an IC-equipped roller compaction equipment is a real-time area mapping of the compacted lift stiffness as captured by the IC measure. Data was collected to evaluate the correlation between each of two IC measures—compaction meter value (CMV) and machine drive power (MDP)—and in situ embankment quality test measures, the chief in situ test being the dynamic cone penetrometer (DCP) test which INDOT uses for soil embankment acceptance testing. Researchers sought to understand how well the IC measures might assess embankment quality as currently evaluated by the in situ measures. Window-averaged IC measures were compared with the in situ DCP test points. For CMV, a variable correlation was found between the average CMV and DCP values from 74 in situ locations. Also, a limited head-to-head comparison of CMV and MDP with the in situ measures provided some indication that MDP should be studied further. Lessons were learned regarding the elimination of bias in future correlation studies, critical provisions to facilitate best data quality, and important aspects of data management. IC technology holds promise for monitoring the consistency of the soil compaction effort and flagging weak areas in real time during compaction operations. However, further insight is needed regarding the correlation of the DCP measure with both types of IC measures for various soil characterizations and field moisture conditions