586 research outputs found
Cumulative Autoimmunity: T Cell Clones Recognizing Several Self-Epitopes Exhibit Enhanced Pathogenicity
T cell receptor (TCR) recognition is intrinsically polyspecific. In the field of autoimmunity, recognition of both self- and microbial peptides by a single TCR has led to the concept of molecular mimicry. However, findings made by our group and others clearly demonstrate that a given TCR can also recognize multiple distinct self-peptides. Based on experimental data we argue that recognition of several self-peptides increases the pathogenicity of an autoreactive T cell; a property we refer to as “cumulative autoimmunity.” The mechanisms of such increased pathogenicity, and the implications of cumulative autoimmunity regarding the pathophysiology of T cell-mediated autoimmune diseases will be discussed
Environmental Health Indicators: A review of initiatives worldwide
Purpose
– The extent to which research into the design and development of environmental health indicators (EHIs) has translated into operational programmes is unclear. The purpose of this paper is to identify EHI initiatives worldwide, distil the EHIs and draw lessons from the experience.
Design/methodology/approach
– A systematic internet-based review was undertaken. Programmes were selected for inclusion if they: first, had the ability to monitor both the physical environment and associated health outcomes; and second, the parent agency had the ability to influence policies related to the environment and health.
Findings
– The small number of eligible programmes indicates EHI initiatives are not yet well established, especially in developing countries. The use of indicators was also limited by uncertainties in the exposure-response relationships that they implied, and the consequent inability to translate the indicators into a common measure of health impact. In addition, there is no information on the extent to which the indicators have been applied in decision making, nor on the policy implications of using indicators.
Practical implications
– More effort is needed to encourage the development and use of more balanced and informative sets of indicators, and to evaluate their use and outcomes in terms of health benefits.
Originality/value
– The time is right for a substantial review paper on EHIs as they are now being used by a number of organisations and to the knowledge this is the first review of operational EHI programmes worldwide
Direct characterisation of tuneable few-femtosecond dispersive-wave pulses in the deep UV
Dispersive wave emission (DWE) in gas-filled hollow-core dielectric
waveguides is a promising source of tuneable coherent and broadband radiation,
but so far the generation of few-femtosecond pulses using this technique has
not been demonstrated. Using in-vacuum frequency-resolved optical gating, we
directly characterise tuneable 3fs pulses in the deep ultraviolet generated via
DWE. Through numerical simulations, we identify that the use of a pressure
gradient in the waveguide is critical for the generation of short pulses.Comment: 5 pages, 4 figure
Optimisation of Quantum Trajectories Driven by Strong-field Waveforms
Quasi-free field-driven electron trajectories are a key element of
strong-field dynamics. Upon recollision with the parent ion, the energy
transferred from the field to the electron may be released as attosecond
duration XUV emission in the process of high harmonic generation (HHG). The
conventional sinusoidal driver fields set limitations on the maximum value of
this energy transfer, and it has been predicted that this limit can be
significantly exceeded by an appropriately ramped-up cycleshape. Here, we
present an experimental realization of such cycle-shaped waveforms and
demonstrate control of the HHG process on the single-atom quantum level via
attosecond steering of the electron trajectories. With our optimized optical
cycles, we boost the field-ionization launching the electron trajectories,
increase the subsequent field-to-electron energy transfer, and reduce the
trajectory duration. We demonstrate, in realistic experimental conditions, two
orders of magnitude enhancement of the generated XUV flux together with an
increased spectral cutoff. This application, which is only one example of what
can be achieved with cycle-shaped high-field light-waves, has farreaching
implications for attosecond spectroscopy and molecular self-probing
Attosecond streaking of photoelectron emission from disordered solids
Attosecond streaking of photoelectrons emitted by extreme ultraviolet light
has begun to reveal how electrons behave during their transport within simple
crystalline solids. Many sample types within nanoplasmonics, thin-film physics,
and semiconductor physics, however, do not have a simple single crystal
structure. The electron dynamics which underpin the optical response of
plasmonic nanostructures and wide-bandgap semiconductors happen on an
attosecond timescale. Measuring these dynamics using attosecond streaking will
enable such systems to be specially tailored for applications in areas such as
ultrafast opto-electronics. We show that streaking can be extended to this very
general type of sample by presenting streaking measurements on an amorphous
film of the wide-bandgap semiconductor tungsten trioxide, and on
polycrystalline gold, a material that forms the basis of many nanoplasmonic
devices. Our measurements reveal the near-field temporal structure at the
sample surface, and photoelectron wavepacket temporal broadening consistent
with a spread of electron transport times to the surface
Gene gun-mediated DNA vaccination enhances antigen-specific immunotherapy at a late preclinical stage of type 1 diabetes in nonobese diabetic mice
Type 1 diabetes (T1D) is characterized by the T cell mediated destruction of the insulin producing β cells. Antigen-specific immunotherapies are used to selectively tolerize β cell-specific pathogenic T cells either directly, or indirectly through the induction of immunoregulatory T cells. A key concern of antigen-specific immunotherapy is exacerbating autoimmunity. We compared the T cell reactivity and efficacy induced by plasmid DNA (pDNA) encoding glutamic acid decarboxylase 65 (GAD65) administered via intramuscular versus gene gun vaccination in NOD mice at a late preclinical stage of T1D. Whereas intramuscular injection of pGAD65 promoted a predominant type 1 CD4+ T cell response and failed to suppress ongoing β cell autoimmunity, gene gun vaccination preferentially induced IL-4 secreting CD4+ T cells and significantly delayed the onset of diabetes. These findings demonstrate that gene gun delivery of autoantigen-encoding pDNA preferentially elicits immunoregulatory T cells and offers a safe, effective mode of pDNA vaccination for the treatment of T1D and other autoimmune diseases
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