Induction of Graft-Versus-Leukaemia Activity Following Bone Marrow Transplantation for Chronic Myeloid Leukaemia

This thesis describes the induction of in vitro graft-versus-leukaemia (GVL) activity following bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML)

The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier.

TRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in what is likely an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the leak K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. We speculate on why nodes of Ranvier contain a mechanosensitive K+ channel

Reduced Intensity Conditioning for Allogeneic Hematopoietic Cell Transplantation: Current Perspectives

AbstractAllogeneic HCT after myeloablative conditioning is an effective therapy for patients with hematologic malignancies. In an attempt to extend this therapy to older patients or those with comorbidities, reduced intensity or truly nonmyeloablative regimens have been developed over the past decade. The principle underlying reduced intensity regimens is to provide some tumor kill with lessened regimen-related morbidity and mortality and then rely on graft-versus-tumor (GVT) effects to eradicate remaining malignant cells, whereas nonmyeloablative regimens rely primarily on GVT effects. In this article, 3 representative approaches are described, demonstrating the clinical application for hematopoietic and nonhematopoietic malignancies. Current challenges include controlling GVHD while allowing GVT to occur. In the future, clinical trials using reduced intensity and nonmyeloablative conditioning will be compared with myeloablative conditioning in selected malignancies to extend the application to standard-risk patients

On the conservation of helicity in a chiral medium

We consider the energy and helicity densities of circularly polarised light within a lossless chiral medium, characterised by the chirality parameter β. A form for the helicity density is introduced, valid to first order in β, that produces a helicity of ±\hbar per photon for right and left circular polarisation, respectively. This is in contrast to the result obtained if we use the form of the helicity density employed for linear media. We examine the helicity continuity equation, and show that this modified form of the helicity density is required for consistency with the dual symmetry condition of a chiral medium with a constant value of ε/μ. Extending the results to arbitrary order in β establishes an exact relationship between the energy and helicity densities in a chiral medium

On the conservation of helicity in a chiral medium

We consider the energy and helicity densities of circularly polarised light within a lossless chiral medium, characterised by the chirality parameter β. A form for the helicity density is introduced, valid to first order in β, that produces a helicity of ±\hbar per photon for right and left circular polarisation, respectively. This is in contrast to the result obtained if we use the form of the helicity density employed for linear media. We examine the helicity continuity equation, and show that this modified form of the helicity density is required for consistency with the dual symmetry condition of a chiral medium with a constant value of ε/μ. Extending the results to arbitrary order in β establishes an exact relationship between the energy and helicity densities in a chiral medium

Optical helicity and chirality: conservation and sources

We consider the helicity and chirality of the free electromagnetic field, and advocate the former as a means of characterising the interaction of chiral light with matter. This is in view of the intuitive quantum form of the helicity density operator, and of the dual symmetry transformation generated by its conservation. We go on to review the form of the helicity density and its associated continuity equation in free space, in the presence of local currents and charges, and upon interaction with bulk media, leading to characterisation of both microscopic and macroscopic sources of helicity

Continuous Symmetries and Conservation Laws in Chiral Media

Locally conserved quantities of the electromagnetic field in lossless chiral media are derived from Noether's theorem, including helicity, chirality, momentum, and angular momentum, as well as the separate spin and orbital components of this last quantity. We discuss sources and sinks of each in the presence of current densities within the material, and in some cases, as also generated by inhomogeneity of the medium. A previously obtained result connecting sources of helicity and energy within chiral materials is explored, revealing that association between the two quantities is not restricted to chiral media alone. Rather, it is analogous to the connection between the momentum, and the spin and orbital components of the total angular momentum. The analysis reveals a new quantity, appearing as the "orbital" counterpart of the helicity density in classical electromagnetism

Strengthening the global system of protected areas post-2020: A perspective from the IUCN World Commission on Protected Areas

Protected areas are the cornerstones of biodiversity conservation and have never been more relevant than at the present time when the world is facing both a biodiversity and a climate change crisis. The International Union for Conservation of Nature (IUCN) World Commission on Protected Areas (WCPA) has been helping to set global standards and best practice guidelines in protected area planning and management for 60 years. Following this guidance, many countries have made significant progress toward their Aichi Target 11 commitments under the Convention on Biological Diversity (CBD). The global community will be coming together at the 15th Conference of the Parties of the CBD to set new biodiversity conservation targets for the next decade, as milestones to 2050 and a vision of “a world living in harmony with nature.” This paper lays out the WCPA perspective on priorities for supporting effective protected and conserved areas for the post-2020 era