## Archive for May, 2021

### From spectral to nonlinear instability, part 2

May 21, 2021

Here I want to extend the discussion of nonlinear instability in the previous post to the infinite-dimensional case. To formulate the problem fix a Banach space $X$. If the starting point is a system of PDE then finding the right $X$ might be a non-trivial task and the best choice might depend on which application we have in mind. We consider an abstract equation of the form $\frac{du}{dt}=Au+F(u)$. Here $t\mapsto u(t)$ is a mapping from an interval to $X$. $A$ is a linear operator which may be unbounded. In fact the case I am most interested in here is that where $A$ is the generator of a strongly continuous semigroup of linear operators on $X$. Hence $A$ may not be globally defined on $X$. It will be assumed that $F$ is globally defined on $X$. This is not a restriction in the applications I have in mind although it might be in other interesting cases. In this setting it is necessary to think about how a solution should be defined. In fact we will define a solution of the above equation with initial value $v$ to be a continuous solution of the integral equation $u(t)=e^{tA}v+\int_0^t e^{(t-\tau)A}F(u(\tau))d\tau$. Here $e^{tA}$ is not to be thought of literally as an exponential but as an element of the semigroup generated by $A$. When $A$ is bounded then $e^{tA}$ is really an exponential and the solution concept used here is equivalent to usual concept of solution for an ODE in a Banach space. Nonlinear stability can be defined just as in the finite-dimensional case, using the norm topology. In general the fact that a solution remains in a fixed ball as long as it exists may not ensure global existence, in contrast to the case of finite dimension. We are attempting to prove instability, i.e. to prove that solutions leave a certain ball. Hence it is convenient to introduce the convention that a solution which ceases to exist after finite time is deemed to have left the ball. In other words, when proving nonlinear instability we may assume that the solution $u$ being considered exists globally in the future. What we want to show is that there is an $\epsilon>0$ such that for any $\delta>0$ there are solutions which start in the ball of radius $\delta$ about $x_0$ and leave the ball of radius $\epsilon$ about that point.

The discussion which follows is based on a paper called ‘Spectral Condition for Instability’ by Jalal Shatah and Walter Strauss. At first sight their proof looks very different from the proof I presented in the last post and here I want to compare them, with particular attention to what happens in the finite-dimensional case. We want to show that the origin is nonlinearly unstable under the assumption that the spectrum of $A$ intersects the half of the complex plane where the real part is positive. In the finite-dimensional case this means that $A$ has an eigenvalue with positive real part. The spectral mapping theorem relates this to the situation where the spectrum of $e^A$ intersects the exterior of the unit disk. In the finite-dimensional case it means that there is an eigenvalue with modulus $\mu$ greater than one. We now consider the hypotheses of the Theorem of Shatah and Strauss. The first is that the linear operator $A$ occurring in the equation generates a strongly continuous semigroup. The second is that the spectrum of $e^A$ meets the exterior of the unit disk. The third is that in a neighbourhood of the origin the nonlinear term can be estimated by a power of the norm greater than one. The proof of nonlinear instability is based on three lemmas. We take $e^\lambda$ to be a point of the spectrum of $e^A$ whose modulus is equal to the spectral radius. In the finite-dimensional case this would be an eigenvalue and we would consider the corresponding eigenvector $v$. In general we need a suitable approximate analogue of this. Lemma 1 provides for this by showing that $e^\lambda$ belongs to the approximate point spectrum of $e^A$. Lemma 2 then shows that there is a $v$ whose norm grows at a rate no larger than $e^{{\rm Re}\lambda t}$ and is such that the norm of the difference between $e^Av$ and $e^{{\rm Re}\lambda t}v$ can be controlled. Lemma 3 shows that the growth rate of the norm of $e^A$ is close to $e^{{\rm Re}\lambda t}$. In the finite-dimensional case the proofs of Lemma 1 and Lemma 2 are trivial. In Lemma 3 the lower bound is trivial in the finite-dimensional case. To get the upper bound in that case a change of basis can be used to make the off-diagonal entries in the Jordan normal form as small as desired. This argument is similar to that used to treat $A_c$ in the previous post. In the theorem we choose a ball $B$ such that instability corresponds to leaving it. As long as a solution remains in that ball the nonlinearity is under good control. The idea is to show that as long as the norm of the initial condition is sufficiently small the contribution of the nonlinear term on the right hand side of the integral equation will remain small compared to that coming from the linearized equation, which is growing at a known exponential rate. The details are complicated and are of course the essence of the proof. I will not try to explain them here.

### My COVID-19 vaccination

May 14, 2021

In Germany vaccination against COVID-19 has been going slowly compared to some other places. One of the leading vaccines was developed by Biontech, a company based in Mainz, which is where I live. Due to this and my impression that that vaccine is very good my first choice would have been to get the Biontech vaccine. In the end things turned out differently. The Biontech vaccine is the one which has been given most often in Germany but the number of vaccinations have been limited by the available supply. The vaccine developed by AstraZenenca has also been used here but has acquired a bad reputation. There were several reasons for that. One is the bad relations of the company to the media. Another is the occurrence of rare side effects involving thromboses. A third is that the publicly quoted efficiency of preventing the illness is much less for AstraZeneca than for Biontech (80% compared to 95%). A fourth is that the waiting time between the first and second injections is longer for AstraZeneca (12 instead of 6 weeks). Despite these things my wife and I decided to get vaccinated with the product from AstraZeneca and had our first injections today. Here I want to explain why we did so and discuss some more general related issues.

I already mentioned that AstraZeneca became unpopular. In connection with the thromboses it was only recommended by the Paul Ehrlich Institute (the official body for such things in Germany) for people over sixty. The argument was that since people over sixty had a higher probability of serious consequences if they got infected the net benefit was positive for them. Doctors were having problems getting rid of their doses. However the situation is very dynamic. Although AstraZeneca is still not recommended for people under 60 (like myself) and it is not administered to them in the official vaccination centres doctors (GP’s and specialists) are allowed to vaccinate people under 60 with that product if they inform them about the risks. They are also allowed to reduce the waiting time between the injections. These political moves have led to many people (particularly young people) wanting to get vaccinated with AstraZeneca. The result is that now instead of being hard to get rid of the AstraZeneca vaccine is scarce. Thus now there is a lot of competition and the whole process is quite chaotic. We were lucky that my wife was offered a vaccination with AstraZeneca at a time when this seemed like asking for a favour rather than offering to do a favour. She asked if I could also be vaccinated by the same doctor and got a positive answer. This was our good fortune.

It was still not clear to us whether we should accept the offer. It is in the nature of the situation that many things concerning the disease and the vaccination are simply not known. On the other hand the amount of information available is huge. All this makes a rational decision difficult. From my point of view the thromboses were so rare that they did not influence my decision at all. The combination of the earlier availability of AstraZeneca for us with the longer waiting time meant that it was not clear which option (taking AstraZeneca now or waiting for Biontech) would lead to being fully immunized sooner. We did not want to shorten the interval for the AstraZeneca vaccination (which our doctor would have accepted) for a reason I will discuss later. A reason for making the choice we did was that this gave the feeling of finally making some progress. In the comparison of the efficiencies of the two products it is important to know that if the criterion considered is the risk of serious illness or hospitalization then according to the official figures AstraZeneca is at least as good as Biontech (both at least 95%). In any case, it was a good feeling to know that we had received one dose of the vaccine. A few hours later I have not noticed any side-effects whatsoever.

Let me return to the question of shortening the time between the injections for AstraZeneca. There is some evidence that this decreases the efficiency of the vaccinations and I have read about two possible mechanisms for this which seem to me at least plausible. The first is connected with the phenomenon of affinity maturation. The first B cells which are activated in response to a certain antigen can undergo somewhat random mutations. This means that the population of B cells becomes rather heterogeneous. The different variants then compete with each other in such a way that those which bind most strongly to the antigen come to dominate the population. In this way the quality of the antibodies is increased. If a second vaccination is given too soon it can interrupt the affinity maturation initiated by the first vaccination before the antibodies have been optimized. The second mechanism is as follows. The immune reponse against the antigen remains active for some time after the vaccination. If second vaccination is given while that is still the case then the antibodies generated in the first vaccination can bind to the vector viruses coming from the second vaccination and prevent them from achieving their intended purpose. These are not established facts but I prefer to have plausible hypotheses than a complete lack of a possible explanation.