Viral evolution under the pressure of an adaptive immune system - optimal mutation rates for viral escape

Based on a recent model of evolving viruses competing with an adapting immune system [1], we study the conditions under which a viral quasispecies can maximize its growth rate. The range of mutation rates that allows viruses to thrive is limited from above due to genomic information deterioration, and from below by insufficient sequence diversity, which leads to a quick eradication of the virus by the immune system. The mutation rate that optimally balances these two requirements depends to first order on the ratio of the inverse of the virus' growth rate and the time the immune system needs to develop a specific answer to an antigen. We find that a virus is most viable if it generates exactly one mutation within the time it takes for the immune system to adapt to a new viral epitope. Experimental viral mutation rates, in particular for HIV (human immunodeficiency virus), seem to suggest that many viruses have achieved their optimal mutation rate. [1] C.Kamp and S. Bornholdt, Phys. Rev. Lett., 88, 068104 (2002)Comment: 5 pages RevTeX including 3 figure

Ponderomotive manipulation of cold subwavelength plasmas

Ponderomotive forces (PFs) induced in cold subwavelength plasmas by an externally applied electromagnetic wave are studied analytically. To this end, the plasma is modeled as a sphere with a radially varying permittivity, and the internal electric fields are calculated by solving the macroscopic Maxwell equations using an expansion in Debye potentials. It is found that the PF is directed opposite to the plasma density gradient, similarly to large-scale plasmas. In case of a uniform density profile, a residual spherically symmetric compressive PF is found, suggesting possibilities for contactless ponderomotive manipulation of homogeneous subwavelength objects. The presence of a surface PF on discontinuous plasma boundaries is derived. This force is essential for a microscopic description of the radiation-plasma interaction consistent with momentum conservation. It is shown that the PF integrated over the plasma volume is equivalent to the radiation pressure exerted on the plasma by the incident wave. The concept of radiative acceleration of subwavelength plasmas, proposed earlier, is applied to ultracold plasmas. It is estimated that these plasmas may be accelerated to keV ion energies, resulting in a neutralized beam with a brightness comparable to that of current high-performance ion sources.Comment: 16 pages, 6 figure

Classical formulations of the electromagnetic self-force of extended charged bodies

Several noncovariant formulations of the electromagnetic self-force of extended charged bodies, as have been developed in the context of classical models of charged particles, are compared. The mathematical equivalence of the various dissimilar self-force expressions is demonstrated explicitly by deriving these expressions directly from one another. The applicability of the self-force formulations and their significance in the wider context of classical charged particle models are discussed.Comment: 21 pages, 1 figur

The staircase method: integrals for periodic reductions of integrable lattice equations

We show, in full generality, that the staircase method provides integrals for mappings, and correspondences, obtained as traveling wave reductions of (systems of) integrable partial difference equations. We apply the staircase method to a variety of equations, including the Korteweg-De Vries equation, the five-point Bruschi-Calogero-Droghei equation, the QD-algorithm, and the Boussinesq system. We show that, in all these cases, if the staircase method provides r integrals for an n-dimensional mapping, with 2r<n, then one can introduce q<= 2r variables, which reduce the dimension of the mapping from n to q. These dimension-reducing variables are obtained as joint invariants of k-symmetries of the mappings. Our results support the idea that often the staircase method provides sufficiently many integrals for the periodic reductions of integrable lattice equations to be completely integrable. We also study reductions on other quad-graphs than the regular 2D lattice, and we prove linear growth of the multi-valuedness of iterates of high-dimensional correspondences obtained as reductions of the QD-algorithm.Comment: 40 pages, 23 Figure

Carotid arterial remodeling - A maladaptive phenomenon in type 2 diabetes but not in impaired glucose metabolism: The Hoorn Study

Background and Purpose-Deteriorating glucose tolerance is associated with an increased cardiovascular disease (CVD) risk. The underlying mechanisms remain unclear. Arterial remodeling is the change in structural properties through time in response to atherogenic and/or hemodynamic alterations and aims to maintain circumferential wall stress constant (

Nebivolol: haemodynamic effects and clinical significance of combined beta-blockade and nitric oxide release.

Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta-blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it causes vasodilatation via interaction with the endothelial L-arginine/nitric oxide (NO) pathway. This dual mechanism of action underlies many of the haemodynamic properties of nebivolol, which include reductions in heart rate and blood pressure (BP), and improvements in systolic and diastolic function. With respect to BP lowering, the NO-mediated effects cause a reduction in peripheral vascular resistance and an increase in stroke volume with preservation of cardiac output. Flow-mediated dilatation and coronary flow reserve are also increased during nebivolol administration. Other haemodynamic effects include beneficial effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity and left ventricular ejection fraction. In addition, nebivolol does not appear to have adverse effects on lipid metabolism and insulin sensitivity like traditional beta-blockers. The documented beneficial haemodynamic effects of nebivolol are translated into improved clinical outcomes in patients with hypertension or heart failure. In patients with hypertension, the incidence of bradycardia with nebivolol is often lower than that with other currently available beta-blockers. This, along with peripheral vasodilatation and NO-induced benefits such as antioxidant activity and reversal of endothelial dysfunction, should facilitate better protection from cardiovascular events. In addition, nebivolol has shown an improved tolerability profile, particularly with respect to events commonly associated with beta-blockers, such as fatigue and sexual dysfunction. Data from SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with Heart Failure) showed that significantly fewer nebivolol versus placebo recipients experienced the primary endpoint of all-cause mortality or cardiovascular hospitalization. The benefits of nebivolol therapy were shown to be cost effective. Thus, nebivolol is an effective and well tolerated agent with benefits over and above those of traditional beta-blockade because of its effects on NO release, which give it unique haemodynamic effects, cardioprotective activity and a good tolerability profile

Development of high-speed directly-modulated DFB and DBR lasers with surface gratings

The conventional distributed feedback and distributed Bragg reflector edge-emitting lasers employ buried gratings, which require two or more epitaxial growth steps. By using lateral corrugations of the ridge-waveguide as surface gratings the epitaxial overgrowth is avoided, reducing the fabrication complexity, increasing the yield and reducing the fabrication cost. The surface gratings are applicable to different materials, including Al-containing ones and can be easily integrated in complex device structures and photonic circuits. Single-contact and multiple contact edge-emitting lasers with laterally-corrugated ridge waveguide gratings have been developed both on GaAs and InP substrates with the aim to exploit the photon-photon resonance in order to extend their direct modulation bandwidth. The paper reports on the characteristics of such surface-grating-based lasers emitting both at 1.3 and 1.55 μm and presents the photon-photon resonance extended small-signal modulation bandwidth (> 20 GHz) achieved with a 1.6 mm long single-contact device under direct modulation. Similarly structured devices, with shorter cavity lengths are expected to exceed 40 GHz smallsignal modulation bandwidth under direct modulatio

Explainable AI for higher cognitive functions: How to provide explanations in the face of increasing complexity

Since the introduction of the term explainable artificial intelligence (XAI), many contrasting definitions and methods have been proposed. This lack of a common framework impedes not only further progress in the field but also the realization of existing regulations, such as the EU’s general data protection regulation on the ‘right to an explanation’ (Goodman & Flaxman, 2017). While some researchers use interpretation algorithms as post-hoc explanations (Samek et al., 2021; Ribeiro, 2016), others argue that we should use models which are interpretable in the first place (Rudin, 2019). Although the latter is important, developers are not always willing to sacrifice accuracy by choosing a less complex interpretable model. Here, we propose a working definition of what explaining an AI model means, focusing on robustness, representativeness, and comprehensibility as central properties, and on the importance of causal links (Miller, 2019). In addition, we suggest starting with simple models and gradually scaling up the level of complexity if necessary, whilst setting a case-specific threshold for its trade-off with accuracy and ensuring that we obtain explanations that meet the requirements of our working definition

Heating mechanisms in radio frequency driven ultracold plasmas

Several mechanisms by which an external electromagnetic field influences the temperature of a plasma are studied analytically and specialized to the system of an ultracold plasma (UCP) driven by a uniform radio frequency (RF) field. Heating through collisional absorption is reviewed and applied to UCPs. Furthermore, it is shown that the RF field modifies the three body recombination process by ionizing electrons from intermediate high-lying Rydberg states and upshifting the continuum threshold, resulting in a suppression of three body recombination. Heating through collisionless absorption associated with the finite plasma size is calculated in detail, revealing a temperature threshold below which collisionless absorption is ineffective.Comment: 14 pages, 7 figure