T cell therapies have demonstrated long-term efficacy and curative potential for the treatment of some cancers. However, their use is limited by damage to bystander tissues, as seen in ...graft-versus-host disease after donor lymphocyte infusion, or "on-target, off-tumor" toxicities incurred in some engineered T cell therapies. Nonspecific immunosuppression and irreversible T cell elimination are currently the only means to control such deleterious responses, but at the cost of abrogating therapeutic benefits or causing secondary complications. On the basis of the physiological paradigm of immune inhibitory receptors, we designed antigen-specific inhibitory chimeric antigen receptors (iCARs) to preemptively constrain T cell responses. We demonstrate that CTLA-4- or PD-1-based iCARs can selectively limit cytokine secretion, cytotoxicity, and proliferation induced through the endogenous T cell receptor or an activating chimeric receptor. The initial effect of the iCAR is temporary, thus enabling T cells to function upon a subsequent encounter with the antigen recognized by their activating receptor. iCARs thus provide a dynamic, self-regulating safety switch to prevent, rather than treat, the consequences of inadequate T cell specificity.
Recent progress in wave packet dynamics based on the insight of Berry pertaining to adiabatic evolution of quantum systems has led to the need for a new property of a Bloch state, the Berry ...curvature, to be calculated from first principles. We report here on the response to this challenge by the ab initio community during the past decade. First we give a tutorial introduction of the conceptual developments we mentioned above. Then we describe four methodologies which have been developed for first-principle calculations of the Berry curvature. Finally, to illustrate the significance of the new developments, we report some results of calculations of interesting physical properties such as the anomalous and spin Hall conductivity as well as the anomalous Nernst conductivity and discuss the influence of the Berry curvature on the de Haas-van Alphen oscillation.
We show that the N(1440) Roper resonance naturally appears in the nuclear model with explicit mesons as a structure in the continuum spectrum of the physical proton, which in this calculation is made ...of a bare nucleon dressed with a pion cloud.
In one dimension, the study of magnetism dates back to the dawn of quantum mechanics when Bethe solved the famous Heisenberg model that describes quantum behaviour in magnetic systems. In the last ...decade, one-dimensional (1D) systems have become a forefront area of research driven by the realization of the Tonks-Girardeau gas using cold atomic gases. Here we prove that 1D fermionic and bosonic systems with strong short-range interactions are solvable in arbitrary confining geometries by introducing a new energy-functional technique and obtaining the full spectrum of energies and eigenstates. As a first application, we calculate spatial correlations and show how both ferro- and antiferromagnetic states are present already for small system sizes that are prepared and studied in current experiments. Our work demonstrates the enormous potential for quantum manipulation of magnetic correlations at the microscopic scale.
A nuclear model is proposed where the nucleons interact by emitting and absorbing mesons, and where the mesons are treated explicitly. A nucleus in this model finds itself in a quantum superposition ...of states with different number of mesons. Transitions between these states hold the nucleus together. The model—in its simplest incarnation—is applied to the deuteron, where the latter becomes a superposition of a neutron-proton state and a neutron-proton-meson state. Coupling between these states leads to an effective attraction between the nucleons and results in a bound state with negative energy, the deuteron. The model is able to reproduce the accepted values for the binding energy and the charge radius of the deuteron. The model, should it work in practice, has several potential advantages over the existing non-relativistic few-body nuclear models: the reduced number of model parameters, natural inclusion of few-body forces, and natural inclusion of mesonic physics.
We apply the nuclear model with explicit mesons to photoproduction of neutral pions off protons at the threshold. In this model the nucleons do not interact with each other via a potential but rather ...emit and absorb mesons that are treated explicitly on equal footing with the nucleons. We calculate the total cross section of the reaction for energies close to threshold and compare the calculations with available experimental data. We show that the model is able to reproduce the experimental data and determine the range of the parameters where the model is compatible with the experiment.
We consider the first initial–boundary value problem for homogeneous second-order parabolic systems with Dini continuous coefficients in a semibounded domain
on the plane with a curvilinear lateral ...boundary that is nonsmooth at
. The existence of a solution of this problem in the class
is proved by the method of boundary integral equations.
We investigate the emergence of halos and Efimov states in nuclei by use of a newly designed model that combines self-consistent mean-field and three-body descriptions. Recent interest in neutron ...heavy calcium isotopes makes ^{72}Ca (^{70}Ca+n+n) an ideal realistic candidate on the neutron dripline, and we use it as a representative example that illustrates our broadly applicable conclusions. By smooth variation of the interactions we simulate the crossover from well-bound systems to structures beyond the threshold of binding, and find that halo configurations emerge from the mean-field structure for three-body binding energy less than ∼100 keV. Strong evidence is provided that Efimov states cannot exist in nuclei. The structure that bears the most resemblance to an Efimov state is a giant halo extending beyond the neutron-core scattering length. We show that the observable large-distance decay properties of the wave function can differ substantially from the bulk part at short distances, and that this evolution can be traced with our combination of few- and many-body formalisms. This connection is vital for interpretation of measurements such as those where an initial state is populated in a reaction or by a beta decay.
The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC
) targets at ISOLDE, CERN. This study focuses on the release ...curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per
C are presented for
Ac, several Ra and Fr isotopes in the mass ranges 214
A
233 and 205
A
231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.
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