Retroviral insertions in the VISION database identify molecular pathways in mouse lymphoid leukemia and lymphoma

AKXD recombinant inbred (RI) strains develop a variety of leukemias and lymphomas due to somatically acquired insertions of retroviral DNA into the genome of hematopoetic cells that can mutate cellular proto-oncogenes and tumor suppressor genes. We generated a new set of tumors from nine AKXD RI strains selected for their propensity to develop B-cell tumors, the most common type of human hematopoietic cancers. We employed a PCR technique called viral insertion site amplification (VISA) to rapidly isolate genomic sequence at the site of provirus insertion. Here we describe 550 VISA sequence tags (VSTs) that identify 74 common insertion sites (CISs), of which 21 have not been identified previously. Several suspected proto-oncogenes and tumor suppressor genes lie near CISs, providing supportive evidence for their roles in cancer. Furthermore, numerous previously uncharacterized genes lie near CISs, providing a pool of candidate disease genes for future research. Pathway analysis of candidate genes identified several signaling pathways as common and powerful routes to blood cancer, including Notch, E-protein, NFκB, and Ras signaling. Misregulation of several Notch signaling genes was confirmed by quantitative RT-PCR. Our data suggest that analyses of insertional mutagenesis on a single genetic background are biased toward the identification of cooperating mutations. This tumor collection represents the most comprehensive study of the genetics of B-cell leukemia and lymphoma development in mice. We have deposited the VST sequences, CISs in a genome viewer, histopathology, and molecular tumor typing data in a public web database called VISION (Viral Insertion Sites Identifying Oncogenes), which is located at http://www.mouse-genome.bcm.tmc.edu/vision

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Challenges in Rheological Characterization of Cement Pastes using a Parallel-Plates Geometry

Cement-based materials are characterized as complex suspensions that may experience a thixotropic behavior caused by physical and chemical phenomena. The characterization and understanding of the rheological properties of cement-based materials have become essential with the introduction of 3D printing in field of civil engineering. Therefore, there is a need to accurately measure such properties to obtain repeatable and consistent results. To measure the rheological properties, different geometries are available, such as vane, parallel-plates, or coaxial cylinders: These are the most used for cement-based materials. Although, there are no specific guidelines on how to select the appropriate geometry for the material that will be tested. Proper understanding of the advantages and disadvantages as well as the limitations of each geometry should be taken into account. Since parallel-plates is a common tool used to evaluate fresh cement-based materials, due to its simplicity, the small sample volume required and the variable gap that can simulate the distance between the aggregates. This paper discusses the major challenges and issues encountered when using parallel-plates geometry to measure the rheological properties of cement-based suspensions under shear. Some issues such as wall slip, sample spill, dryness, particles sedimentation, non-uniform shear rate applied, etc. can be prevented but the user should be aware of these problems

Organizations Behaving Badly: When Are Discreditable Actions Likely to Damage Organizational Reputation?

discreditable action, misconduct, organization, reputation, stigma,