Determination of Moisture Diffusion Coefficient at Low Suctions Using Thermal Conductivity Sensors

The main aim of this research is to determine the drying and wetting moisture coefficients in unsaturated soils at low suctions using thermal conductivity sensors. The performance of a geotechnical structure can be strongly influenced by the moisture conditions in the soil. The movement of water in unsaturated soils can be described by determining the diffusion coefficient of the soil. The diffusion coefficient can be determined by the analysis of suction changes with time in the soil. The suction measurements can be made using different techniques. In this research study, the suction measurements were conducted using thermal conductivity sensors and thermocouple psychrometers. Mitchell (1979) proposed an approach to determine the diffusion coefficient of the soil. Mitchell's proposal of one dimensional analysis using rate of moisture flow through soil provides a simple, economical and reliable framework for determining the drying and wetting diffusion coefficients in a geotechnical laboratory. The calibration and the operation of the thermal conductivity sensors and the thermocouple psychrometers are explained in detail in this research study. Using the two devices, the drying and wetting diffusion coefficients were determined and the comparison study has been conducted between the two approaches. With the reliable estimate of the diffusion coefficient, the moisture movement can be predicted in a soil massCivil Engineerin

DRYING SHRINKAGE PROBLEMS IN HIGH PI SUBGRADE SOILS

The main objective of this study was to investigate the longitudinal cracking in pavements due to drying shrinkage of high PI subgrade soils. The study involved laboartory soil testing and modeling. The shrinkage cracks usually occur within the vicinity of the edge of the pavement where moisture boundary conditions play a significant role in the behavior of expansive subgrade soils. The study investigated the shrinkage problems in pavement subgrade soils at four sites in Oklahoma. The soil specimens collected from the sites were tested for the basic index properties as well as soil suction and unsaturated diffusivity measurements. Various ranges of the test results have been implemented in suction profile and tensile stress prediction models for evaluating the typical suction changes and the corresponding tensile stresses in subgrade soils.Final report, October 2011-December 2013N

Gene correction for SCID-X1 in long-term hematopoietic stem cells.

Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system. Here we describe an approach for X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration of a cDNA into the endogenous start codon to functionally correct disease-causing mutations throughout the gene. Using a CRISPR-Cas9/AAV6 based strategy, we achieve up to 20% targeted integration frequencies in LT-HSCs. As measures of the lack of toxicity we observe no evidence of abnormal hematopoiesis following transplantation and no evidence of off-target mutations using a high-fidelity Cas9 as a ribonucleoprotein complex. We achieve high levels of targeting frequencies (median 45%) in CD34+ HSPCs from six SCID-X1 patients and demonstrate rescue of lymphopoietic defect in a patient derived HSPC population in vitro and in vivo. In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl

Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells.

The original version of this Article omitted the following from the Acknowledgements: G.B. acknowledges the support from the Cancer Prevention and Research Institute of Texas (RR140081 and RR170721).This has now been corrected in both the PDF and HTML versions of the Article

In vivo visualization and molecular targeting of the cardiac conduction system

Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against the CCS, allowing for the visualization of the CCS in vivo following a single intravenous injection in mice. These optical imaging tools showed high sensitivity, specificity, and resolution, with no adverse effects on CCS function. Further, with the goal of creating a viable prototype for human use, we generated a fully human monoclonal Fab that similarly targets the CCS with high specificity. We demonstrate that, when conjugated to an alternative cargo, this Fab can also be used to modulate CCS biology in vivo, providing a proof of principle for targeted cardiac therapeutics. Finally, in performing differential gene expression analyses of the entire murine CCS at single-cell resolution, we uncovered and validated a suite of additional cell surface markers that can be used to molecularly target the distinct subcomponents of the CCS, each prone to distinct life-threatening arrhythmias. These findings lay the foundation for translational approaches targeting the CCS for visualization and therapy in cardiothoracic surgery, cardiac imaging, and arrhythmia management

Gene correction for SCID-X1 in long-term hematopoietic stem cells

Gene correction in hematopoietic stem cells could be a powerful way to treat monogenic diseases of the blood and immune system. Here the authors develop a strategy using CRISPR-Cas9 and an aAdeno-Associated vVirus(AAV)-delivered IL2RG cDNA to correct X-linked sSevere Ccombined iImmunodeficiency (SCID-X1) with a high success rate

Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells

The original version of this Article omitted the following from the Acknowledgements: “G.B. acknowledges the support from the Cancer Prevention and Research Institute of Texas (RR140081 and RR170721).”This has now been corrected in both the PDF and HTML versions of the Article

Gene correction for SCID-X1 in long-term hematopoietic stem cells.

Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system. Here we describe an approach for X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration of a cDNA into the endogenous start codon to functionally correct disease-causing mutations throughout the gene. Using a CRISPR-Cas9/AAV6 based strategy, we achieve up to 20% targeted integration frequencies in LT-HSCs. As measures of the lack of toxicity we observe no evidence of abnormal hematopoiesis following transplantation and no evidence of off-target mutations using a high-fidelity Cas9 as a ribonucleoprotein complex. We achieve high levels of targeting frequencies (median 45%) in CD34+ HSPCs from six SCID-X1 patients and demonstrate rescue of lymphopoietic defect in a patient derived HSPC population in vitro and in vivo. In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl

The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans

Molecular characterization of cell types using single-cell transcriptome sequencing is revolutionizing cell biology and enabling new insights into the physiology of human organs. We created a human reference atlas comprising nearly 500,000 cells from 24 different tissues and organs, many from the same donor. This atlas enabled molecular characterization of more than 400 cell types, their distribution across tissues, and tissue-specific variation in gene expression. Using multiple tissues from a single donor enabled identification of the clonal distribution of T cells between tissues, identification of the tissue-specific mutation rate in B cells, and analysis of the cell cycle state and proliferative potential of shared cell types across tissues. Cell type-specific RNA splicing was discovered and analyzed across tissues within an individual