Immunoincompetence after allogeneic hematopoietic stem cell transplantation (HSCT) affects in particular the T-cell lineage and is associated with an increased risk for infections, graft failure and malignant relapse. To generate large numbers of T-cell precursors for adoptive therapy, we cultured mouse hematopoietic stem cells (HSCs) in vitro on OP9 mouse stromal cells expressing the Notch-1 ligand Delta-like-1 (OP9-DL1). We infused these cells, together with T-cell-depleted mouse bone marrow or purified HSCs, into lethally irradiated allogeneic recipients and determined their effect on T-cell reconstitution after transplantation. Recipients of OP9-DL1-derived T-cell precursors showed increased thymic cellularity and substantially improved donor T-cell chimerism (versus recipients of bone marrow or HSCs only). OP9-DL1-derived T-cell precursors gave rise to host-tolerant CD4+ and CD8+ populations with normal T-cell antigen receptor repertoires, cytokine secretion and proliferative responses to antigen. Administration of OP9-DL1-derived T-cell precursors increased resistance to infection with Listeria monocytogenes and mediated significant graft-versus-tumor (GVT) activity but not graft-versus-host disease (GVHD). We conclude that the adoptive transfer of OP9-DL1-derived T-cell precursors markedly enhances T-cell reconstitution after transplantation, resulting in GVT activity without GVHD.
Small satellite systems enable whole new class of missions for navigation, communications, remote sensing and scientific research for both civilian and military purposes. As individual spacecraft are limited by the size, mass and power constraints, mass-produced small satellites in large constellations or clusters could be useful in many science missions such as gravity mapping, tracking of forest fires, finding water resources, etc. The proliferation of small satellites will enable a better understanding of the near-Earth environment and provide an efficient and economical means to access the space through the use of multi-satellite solution. Constellation of satellites provide improved spatial and temporal resolution of the target. Small satellite constellations contribute innovative applications by replacing a single asset with several very capable spacecraft which opens the door to new applications. Future space missions are envisioned to become more complex and operate farther from Earth which will need to support autonomous operations with minimal human intervention. With increasing levels of autonomy, there will be a need for remote communication networks to enable communication between spacecraft. These space based networks will need to configure and maintain dynamic routes, manage intermediate nodes, and reconfigure themselves to achieve mission objectives. Hence, inter-satellite communication is a key aspect when satellites fly in formation. In this paper, we present the various researches being conducted in the small satellite community for implementing inter-satellite communications based on the Open System Interconnection (OSI) model. This paper also reviews the various design parameters applicable to the first three layers of the OSI model, i.e., physical, data link and network layer. Based on the survey, we also present a comprehensive list of design parameters useful for achieving inter-satellite communications for multiple small satellite missions. Specific topics include proposed solutions for some of the challenges faced by small satellite systems, enabling operations using a network of small satellites, and some examples of small satellite missions involving formation flying aspects.
Peritoneal dialysis (PD) penetration in India remains low despite the huge chronic kidney disease burden and unmet need for renal replacement therapy (RRT). In order to understand the socioeconomic reasons that govern patients' preference for hemodialysis (HD), we carried out an opinion survey among prevalent in-center HD patients at our institution using a multiple response questionnaire that was verbally administered to them at the dialysis facility by the investigators. Close to 80% were self-financed and 49.5% were on twice weekly HD. Despite the majority (95%) receiving RRT education from a nephrologist, 43.4% were not aware of PD as an RRT modality. The treating nephrologist's recommendation was the most important reason given for choosing HD (77.8%) and not choosing PD (69.7%). Other reasons for not choosing PD included lack of a dedicated caregiver or "clean area" at home (15.1%), fear of infection (15.1%), disruption of work (14.1%), and the high cost of PD (7%). The perceived advantages of HD over PD were greater convenience because of need for only twice or thrice weekly sessions (61%), supervised care received in a hospital setting (28.8%), and less disruption of the patient's and family's routine (22%). We discuss the implications of these findings and what policy makers and nephrologists in India and other developing countries can do to improve PD penetration and utilization.
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