Continuous Acquisition of MHC:Peptide Complexes by Recipient Cells Contributes to the Generation of Anti-Graft CD8+ T Cell Immunity

Understanding the evolution of the direct and indirect pathways of allorecognition following tissue transplantation is essential in the design of tolerance‐promoting protocols. On the basis that donor bone marrow–derived antigen‐presenting cells are eliminated within days of transplantation, it has been argued that the indirect response represents the major threat to long‐term transplant survival, and is consequently the key target for regulation. However, the detection of MHC transfer between cells, and particularly the capture of MHC:peptide complexes by dendritic cells (DCs), led us to propose a third, semidirect, pathway of MHC allorecognition. Persistence of this pathway would lead to sustained activation of direct‐pathway T cells, arguably persisting for the life of the transplant. In this study, we focused on the contribution of acquired MHC‐class I on recipient DCs during the life span of a skin graft. We observed that MHC‐class I acquisition by recipient DCs occurs for at least 1 month following transplantation and may be the main source of alloantigen that drives CD8(+) cytotoxic T cell responses. In addition, acquired MHC‐class I:peptide complexes stimulate T cell responses in vivo, further emphasizing the need to regulate both pathways to induce indefinite survival of the graft

Potential sinks for geologic storage of carbon dioxide generated by power plants in North and South Carolina

Duke Energy Progress Energy Santee Cooper Power SCANA CorporationBureau of Economic Geolog

Potential Sinks for Geologic Storage of CO2 Generated in the Carolinas

This document summarizes a scoping study of the current state of knowledge of carbon storage options for our geographic area. The focus is on one aspect of carbon capture and storage—identification of deep saline aquifers in which carbon dioxide (CO2 ) generated in the Carolinas might be stored. The study does not address other aspects of CO2 storage projects, such as capture and compression of the gas, well construction and development, or injection. Transport of CO2 is touched upon in this study but has not been fully addressed. The information contained in this document is primarily from review of published geologic literature and unpublished data. No field data collection has been completed as part of this study. Further work will be necessary to increase confidence in the suitability of the potential CO2 storage sites identified in this report. This study does not address the regulatory, environmental, or public policy issues associated with carbon storage, which are under development at this time.Duke Energy, Progress Energy, Santee Cooper Power, South Carolina Electric and Gas, Electric Power Research Institute (EPRI), Southern States Energy Board (SSEB)Bureau of Economic Geolog

Markers of apoptosis: Methods for elucidating the mechanism of apoptotic cell death from the nervous system

Apoptosis is a highly conserved energy-requiring program for non-inflammatory cell death that is important in both normal physiology and disease. Numerous techniques have been used to study apoptosis. In the nervous system, apoptosis is necessary for normal development, but it also occurs in many acute and chronic pathologic conditions. This review places commonly used markers of apoptosis and their detection in the context of what is now known about the process of apoptosis. We review the potential role of apoptosis in nervous system and neurodegenerative disorders (Alzheimer\u27s disease, Parkinson\u27s disease, and amyotrophic lateral sclerosis). We then describe important morphological, immunocytochemical, and molecular genetic markers for apoptosis, including proteases, signal transduction molecules, and mitochondrial proteins. The possibility of manipulating apoptosis therapeutically in conditions of too many or too few cells is under active investigation

The in vitro and in vivo anti-tumour activity of N-AcMEL-(Fab')2 conjugates.

To increase the accessibility of drug-antibody complexes to tumours and to decrease non-specific binding via Fc receptors N-acetyl-melphalan (N-AcMEL) was conjugated to F(ab')2 fragments. These fragments were synthesised by pepsin degradation of IgG MoAb. Up to 20 molecules of N-AcMEL could be successfully coupled to each F(ab')2 fragment (compared with 25 molecules/intact IgG) with retention of both drug and antibody activity. The N-AcMEL-F(ab')2 conjugates demonstrated specific cytotoxicity in vitro however despite the absence of non specific Fc receptor binding and greater permeability when using F(ab')2 fragments, the N-AcMEL-F(ab')2 and N-AcMEL-IgG conjugates had similar anti-tumour activity in vivo. Conjugates made with whole IgG and F(ab')2 were equally effective in eradicating subcutaneous solid tumours in mice when injected intravenously. The lower immunogenicity of F(ab')2 fragments compared with whole IgG and the similar cytotoxicity of their conjugates, suggests that the F(ab')2 conjugate has greater clinical utility

ENDOCRINE FUNCTION OF THE SURGICALLY REDUCED PANCREAS

The pancreas reduced to 4 or 10 gm. weeks or months previously by partial resection, is able to maintain a normal glycemic level in dogs of about 10 kilos in good condition. When the pancreas is reduced to 4 gm. the capacity for secreting insulin under certain conditions of strain is diminished whereas a pancreas reduced to 10 gm. may have a normal or decreased capacity. This decreased functional capacity is shown: (1) by a longer hyperglycemic curve after the intravenous injection of 1 gm. of glucose per kilo; (2) by the requirement of smaller doses of extract of anterior hypophysis to produce diabetes; and (3) by the longer time required to correct the diabetic hyperglycemia if reduced pancreas is grafted in the neck of pancreatectomized animals. The time to recover is in inverse ratio to the weight of the transplanted pancreatic tissue

Unsteady undular bores in fully nonlinear shallow-water theory

We consider unsteady undular bores for a pair of coupled equations of Boussinesq-type which contain the familiar fully nonlinear dissipationless shallow-water dynamics and the leading-order fully nonlinear dispersive terms. This system contains one horizontal space dimension and time and can be systematically derived from the full Euler equations for irrotational flows with a free surface using a standard long-wave asymptotic expansion. In this context the system was first derived by Su and Gardner. It coincides with the one-dimensional flat-bottom reduction of the Green-Naghdi system and, additionally, has recently found a number of fluid dynamics applications other than the present context of shallow-water gravity waves. We then use the Whitham modulation theory for a one-phase periodic travelling wave to obtain an asymptotic analytical description of an undular bore in the Su-Gardner system for a full range of "depth" ratios across the bore. The positions of the leading and trailing edges of the undular bore and the amplitude of the leading solitary wave of the bore are found as functions of this "depth ratio". The formation of a partial undular bore with a rapidly-varying finite-amplitude trailing wave front is predicted for ``depth ratios'' across the bore exceeding 1.43. The analytical results from the modulation theory are shown to be in excellent agreement with full numerical solutions for the development of an undular bore in the Su-Gardner system.Comment: Revised version accepted for publication in Phys. Fluids, 51 pages, 9 figure

The Effect of low Momentum Quantum Fluctuations on a Coherent Field Structure

In the present work the evolution of a coherent field structure of the Sine-Gordon equation under quantum fluctuations is studied. The basic equations are derived from the coherent state approximation to the functional Schr\"odinger equation for the field. These equations are solved asymptotically and numerically for three physical situations. The first is the study of the nonlinear mechanism responsible for the quantum stability of the soliton in the presence of low momentum fluctuations. The second considers the scattering of a wave by the Soliton. Finally the third problem considered is the collision of Solitons and the stability of a breather. It is shown that the complete integrability of the Sine-Gordon equation precludes fusion and splitting processes in this simplified model. The approximate results obtained are non-perturbative in nature, and are valid for the full nonlinear interaction in the limit of low momentum fluctuations. It is also found that these approximate results are in good agreement with full numerical solutions of the governing equations. This suggests that a similar approach could be used for the baby Skyrme model, which is not completely integrable. In this case the higher space dimensionality and the internal degrees of freedom which prevent the integrability will be responsable for fusion and splitting processes. This work provides a starting point in the numerical solution of the full quantum problem of the interaction of the field with a fluctuation.Comment: 15 pages, 9 (ps) figures, Revtex file. Some discussion expanded but conclusions unchanged. Final version to appear in PR