
The germinal center (GC) is a self-organizing structure produced in the lymphoid follicle during the T-dependent immune response and is an important component of the humoral immune system. However, the impact of the special structure of GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC including the appearance of two specific zones: the dark zone (DZ) and the light zone (LZ), the development of which serves to maintain an effective competition among different cells and promote affinity maturation. A phase transition is discovered in this process, which determines the critical GC volume for a successful growth in both the stochastic and the deterministic model. Further increase of the volume does not make much improvement on the performance. It is found that the critical volume is determined by the distance between the activated B cell receptor (BCR) and the target epitope of the antigen in the shape space. The observation is confirmed in both 2D and 3D simulations and explains partly the variability of the observed GC size.
Citation: Zishuo Yan, Hai Qi, Yueheng Lan. The role of geometric features in a germinal center[J]. Mathematical Biosciences and Engineering, 2022, 19(8): 8304-8333. doi: 10.3934/mbe.2022387
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The germinal center (GC) is a self-organizing structure produced in the lymphoid follicle during the T-dependent immune response and is an important component of the humoral immune system. However, the impact of the special structure of GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC including the appearance of two specific zones: the dark zone (DZ) and the light zone (LZ), the development of which serves to maintain an effective competition among different cells and promote affinity maturation. A phase transition is discovered in this process, which determines the critical GC volume for a successful growth in both the stochastic and the deterministic model. Further increase of the volume does not make much improvement on the performance. It is found that the critical volume is determined by the distance between the activated B cell receptor (BCR) and the target epitope of the antigen in the shape space. The observation is confirmed in both 2D and 3D simulations and explains partly the variability of the observed GC size.
The rapid proliferation of cloud computing, the Internet of Things, and online video applications has led to an exponential surge in network traffic. This causes network capacity to quickly reach its limits, making congestion control a critical issue in ensuring efficient network operation. Since the birth of the Internet, the congestion problem of network transmission has received widespread attention[1,2,3,4,5]. For this reason, many methods to solve network congestion came into being. Traditional queue management policies adopt the "Drop-Tail" policy, which is easy to produce continuous full queue state, and even lead to data flow deadlock and global synchronization. Therefore, active queue management (AQM) has attracted the attention of many scholars[6]. It can effectively mitigates congestion, diminishes packet loss rates, enhances network utilization, and averts network crashes. The initial AQM algorithm introduced is Random Early Detection (RED), which computes the likelihood of packet loss based on the average queue length[7]. Although RED algorithm can effectively control the congestion in the network, the performance of RED algorithm can not adapt to the change of network load because it is sensitive to static parameters. In the following decades, many scholars have improved the RED algorithm[8,9], but these improved RED algorithms have high requirements for parameter tuning and are easily affected by the environment[10]. Due to the lack of systematic theory, the algorithm basically relies on intuition and inspiration, which leads to some problems in stability and robustness. To avoid this problem, Misra established a new TCP/AQM model based on fluid flow theory combined with stochastic differential equations, which laid the foundation for applying control theory to settle the corresponding congestion problem[11]. Due to the complexity of the network, scholars focus on different issues. Ren introduced an AQM algorithm grounded in linear control principles[12]. However, the AQM controller based on linear theory can not well compensate the nonlinearity of the network system, and is vulnerable to the disturbance of unresponsive flow and other factors, its robustness is poor, the stability of the algorithm is difficult to be guaranteed. [13] uses linear matrix inequality (LMI) to linearize the nonlinear model, and compensates the influence of uncertainty in the network through the designed sliding surface. These studies are based on linear systems, ignoring the nonlinear dynamic nature of TCP networks. Therefore, many scholars have proposed congestion control algorithms for nonlinear TCP networks. Liu applies the prescribed performance technology to the TCP/AQM congestion problem, and designs congestion control combined with H∞ control, which can estimate the unknown link capacity[14]. Considering the dynamic nature of the session count during network transmission, Chen adapted the TCP/AQM model into a switching model. Subsequently, a network congestion controller was devised, integrating prescribed performance technology. This designed controller adeptly manages the frequent fluctuations in the number of sessions[15]. Furthermore, certain studies also use intelligent control methods[16], data segmentation methods[17] and various other control methodologies to formulate network congestion controllers. The author develops an AQM algorithm using Neural Network (NN) approaches and fuzzy variable structure control respectively[18,19]. The output weight of radial basis function NN was obtained by particle swarm optimization, and then AQM controller was implemented in [20].
The dynamic nonlinear system of TCP network has saturation characteristics, which may deteriorate the performance of the network system and inducing instability of the system. Therefore, accounting for the saturation characteristics of the control input becomes imperative when designing AQM algorithm[21,22,23,24]. [21] considers the input constraint of the TCP network system, and replaces the non-differentiable saturation function with the smooth differentiable function, the designed AQM algorithm enables the system to obtain better asymptotic stability. [22] designs robust enhanced proportional derivatives affected by input saturation, and solves the controller design problem for linear systems with asymmetric constraints by the scaling small gain theorem. Considering the input saturation within the TCP/AQM system, Shen proposed a new AQM control combined with the prescribed performance control. Employing FLS, the approach effectively addresses error disturbances stemming from input saturation, thereby enhancing the overall control effectiveness of the system.[23]. Similarly, dead zone may exist in the actual dynamic system[25,26,27], although many scholars have noticed the input nonlinearity such as dead zone and saturation, have also proposed corresponding solutions, the existing researches on TCP network congestion control only consider the dynamic characteristics of a single characteristic. So the control problems of multi-type input nonlinearity, particularly those associated with uncertain nonlinearities, remain relatively scarce. In this paper, the effects of dead zone and saturation inputs concurrently on TCP network congestion control are considered at the same time, and the performance of the system is controlled effectively.
In the Internet, under the influence of the environment, there are always some uncertainties in practical TCP network, such as the uncertainty of network parameters and unresponsive User Datagram Protocol (UDP) flows. At present, the most effective solution is to learn the uncertain functions in the nonlinear systems with the neural networks or the fuzzy logical systems[28,29,30,31,32]. Based on the approximate characteristics of FLS, Liu et al. introduced an adaptive fuzzy control scheme to improve the robustness and convergence of nonlinear stochastic switching systems[33]. In the context of a nonlinear system characterized by uncertain function constraints, a fuzzy state observer is devised to estimate the unmeasurable state variables, so that the system state is no longer constrained by the function[34]. Based on the above analysis, the application of FLS in TCP/AQM system can effectively alleviate the congestion problem. Mohammadi et al. proposed a PID controller for TCP/AQM systems with saturated input delay, which reduces packet loss and improves network utilization. In the design process of the controller, fuzzy algorithm is used to approximate the optimal PID control gain[35]. In view of the time-varying number of sessions during network transmission, Chen modified the TCP/AQM model into a switching model and established a network congestion controller combined FLS with prescribed performance technology, the designed controller can cope with frequent changes in the number of sessions[36]. The incorporation of FLS is undertaken to address unknown elements, accompanied by the formulation of a novel practical control law. The designed adaptive tracking controller ensures the actual boundary of all signals in the TCP/AQM network system [37].
At present, in the big data environment, the number of network nodes and data traffic are very large, especially UDP flow represented by audio and video occupy a large amount of bandwidth. Therefore, Controlling traffic for a single node proves challenging in mitigating network congestion. Recognizing this, in the development of a congestion control algorithm, a holistic approach that considers the entire network becomes imperative to effectively avert congestion issues within the expansive realm of big data. Based on this, this paper studies delves into an exploration of an adaptive fuzzy control for AQM network nonlinear systems, incorporating considerations for both saturated input and dead zones. The principal contributions of this study can be summarized in the following three key points.
(1) Considering the unknown response flow and the interplay among network nodes, this paper takes the TCP network as a whole and builds a multi-bottleneck TCP/AQM network model, which can more accurately describe the real network and improve the window utilization.
(2) In this paper, for the first time, the dead zone and saturation input nonlinear characteristics of the network model are considered at the same time, by confining the input within the permissible range, this approach renders the model in this study notably more comprehensive and inclusive.
(3) Combined with the backstepping technique, this paper designs the adaptive fuzzy control algorithm, which guarantees the steady-state and transient performance of the tracking error, allowing the queue length of nodes to effectively track the desired queue length.
The subsequent sections of this paper are structured as follows: Section 2 provides the TCP network model and outlines the preliminaries. Section 3 presents the primary result. To illustrate the effectiveness of the proposed method, Section 4 conducts simulation experiments. Finally, Section 5 summarizes the conclusion.
Building upon Misra's fluid model in 2001, this paper considers the following multi-bottleneck TCP network
{˙Ws,i(t)=Ni(t)Ri(t)−W2s,i(t)2Ni(t)Ri(t)pi(t)˙qi(t)=−Ci(t)+Ws,i(t)Ri(t)−∑nj=1Ws,j(t)Nj(t)+ωi(t) | (2.1) |
where Ws,i(t) is the total congestion window size, Ri(t) is the round-trip delay, qi(t) is the queue length in the router, pi(t) is the probability of packet loss, Ni(t) and Ci(t) is the number of TCP sessions and available link capacity, respectively. ωi(t) is the external disturbance caused by unresponsive flows like UDP flows. i is the i-th network node.
Remark 1. A multi-bottleneck TCP/AQM network is different from a single-bottleneck network in that it contains multiple bottleneck nodes. In the transmission process, the upstream node acts as the sender of the downstream node, and its link capacity is affected by the adjustment of the downstream node to the size of the sender window. Hence, in formulating the network model, this paper takes into account how downstream nodes affect the link capacity of upstream nodes. It is worth noting that the queue capacity of each bottleneck node is usually not the same, making its transmission model different.
Due to the complexity of multi-bottleneck networks, the queue length in single-bottleneck networks is no longer suitable. Therefore, in the congestion control design, this paper considers tracking the queue usage rate qu,i. Assuming the known total number of queues that a single router can accommodate, denoted as qmax, and the queue usage rate of a single router as qu,i=qiqmax, model (2.1) can be reformulated as follows:
{˙Ws,i(t)=Ni(t)Ri(t)−W2s,i(t)2Ni(t)Ri(t)pi(t)˙qu,i(t)=˙qi(t)qmax,i=Ws,i(t)Ri(t)qmax,i−−Ci+∑nj=1aijWs,j(t)Nj(t)qmax,i+ωi(t). | (2.2) |
Let x1,i=qu,i, x2,i=Ws,i(t), Ni∈N+, The network dynamics model (2.2) can be written as
{˙x1,i=fi(x2,i)−−Ci+∑nj=1aijx2,j(t)Nj(t)qmax,i+ωi(t)˙x2,i=gσ(t),i(x2,i)+hσ(t),i(x2,i)ui(t)yi=x1,i | (2.3) |
where fi(x2,i)=x2,iRi(t)qmax,i, gσ(t),i=Nσ(t),i(t)Ri(t), hσ(t),i(x2,i)=−x22,i(t)2Nσ(t),i(t)Ri(t), ui(t)=pi(t), σ(t):[0,∞)→N=1,⋯,Nmax is switching signal.
Assumption 1. Suppose that the unknown disturbance ωi(t) is bounded, and 0≤ωi≤ωmax.
ui(t) is a nonsymmetric dead-zone input nonlinearity which is defined as follows:
D(u)={mr(u−ur),u≥ur0,ul<u<urml(u−ul),u≤ul | (2.4) |
where the parameters ur>0 and ul<0 represent the breakpoints of control signal nonlinearity. ml>0 and mr>0 denote the right slope and the left slope of the dead zone.
Given that the control signal ui(t) for TCP/AQM represents the marking probability, with a value range of [0,1], the system input is constrained by nonlinear saturation as defined by
sat(u)={umax,u>umaxu,−umin≤u≤umax−umin,u<−umin=℘(u)u | (2.5) |
where umax>0 and umin>0 are unknown constants, respectively.
Let's assume umax>mrur and umin>mlul. Defined ℘(u) as follows:
℘(u)={umaxu,u>umax1,−umin≤u≤umax−uminu,u<−umin. | (2.6) |
Obviously, ℘(u)∈R and η≤℘(u)≤1, where η>0 is an unknown constant.
Remark 2. Significantly, both the input dead zone and saturation characteristics of the network model are considered in this paper, which makes the application more extensive.
Thus, according to (2.4–2.6), sat(D(u)) can be characterized as
sat(D(u))={umaxD(u)D(u)=℘(D(u))mr(u−ur),u>umaxmr+urmr(u−ur),umaxmr+ur≥u>umax0,−umin≤u≤umaxml(u−ul),−uminml+ul≤u<−ul−uminD(u)D(u)=℘(D(u))ml(u−ul),u<−uminml+ul. | (2.7) |
Consider the jth IF-THEN rule of the following form:
Rℓ: IF x1 is Fℓ1 and … and xn is Fℓn.
Then y is Gℓ, l=1,2,…,N, where x=[x1,x2,…,xn]T∈Rn, and y∈R are input and output of the FLS, respectively. Fℓi and Gℓ are fuzzy sets in R. By using the singleton fuzzification, the product inference and the center-average defuzzification, the FLS can be given as
y(x)=∑Nℓ=1φℓ∏ni=1μFℓi(ˉxi)∑nℓ=1[∏ni=1μFℓi(ˉxi)] |
where N is the number of IF-THEN rules, ϖj is the point at which fuzzy membership function μPℓ(ϖℓ)=1.
Let
ζℓ(x)=∏ni=1μFℓi(xi)∑Nℓ=1[∏ni=1μFℓi(xi)] |
where ζ(x)=[ζ1(x),ζ2(x),…,ζN(x)]T Then the FLS can be described as
y=φTζ(x). | (2.8) |
Lemma 1. [38] Let f(x) be a continuous function defined on a compact set Ω. Then, for ∀ϵ>0, there exists a FLS (2.8) such that
supx∈Ω|f(x)−φTζ(x)|≤ϵ. | (2.9) |
Lemma 2. (Young's inequality) For ∀(x,y)∈R2, the following inequality holds:
xy≤αpp|x|p+1qαq|y|q, | (2.10) |
where α>0, p>1, q>1, and (p−1)(q−1)=1.
Lemma 3. For 1≤i≤n, there is an unknown constant b>0 that satisfies:
|hσ(t),i|≤b. | (2.11) |
This section introduces an adaptive fuzzy control scheme utilizing the backstepping method for system (2.3). The backstepping design scheme includes n steps. First of all, the transfer error of network nodes is given as follows:
{z1,i=∑nj=1aij(yi−yj)+(yi−yref)z2,i=x2,i−α1,i | (3.1) |
where α1,i is the virtual control law and yref is the tracking objective function.
Theorem 1. Under assumption 1, using virtual control law (3.2), adaptive law (3.3), (3.4) and control law (3.12), multi-bottleneck TCP/AQM system (2.2) exhibits the following characteristics:
(1) The queue length required for the output tracking of the system.
(2) All signals within the closed-loop system are semi-globally uniform and ultimately bounded.
(3) The tracking error of each bottleneck node converges to a small neighborhood near the origin.
Before designing the controller, it is necessary to establish the constants θk,i=‖Φ∗k,i‖2,k=1,2,⋯,n, where ˆθk,i represents the estimation of θk,i, with the estimation error denoted as ˜θk,i=θk,i−ˆθk,i.
Select the virtual control law and adaptive law as follows:
α1,i=Rqmax,idi(Ci+∑nj=1aijxi,jNjqmax,idi+˙qref−12a21z1,iˆθ1,iξT1,iξ1,i). | (3.2) |
˙ˆθ1,i=r12a21z21,iξT1,iξ1,i−τ1,iˆθ1,i. | (3.3) |
˙ˆθ2,i=r22a22z22,iξT2,iξ2,i−τ2,iˆθ2,i. | (3.4) |
Step 1. Consider the following Lyapunov function:
V1,i=12z21,i+12r1˜θ21,i. | (3.5) |
Then, differentiating V1,i with respect to time results in
˙V1,i=z1,i[n∑j=1,j≠iaij(yi−yj)+(yi−yref)]−1r1˜θ1,i˙ˆθ1,i=z1,i[n∑j=1,j≠iaij(fi(x2,i)−Ci+∑nj=1aijx2,jNjqmax,i+ωi(t))−n∑j=1,j≠iaij(fj(x2,j)−Cj+∑nk=1ajkx2,kNkqmax,j−ωi(t))+(fi(x2,i)−Ci+∑nj=1aijx2,jNjqmax,i+ωj(t)−˙qref)]−1r1˜θ1,i˙ˆθ1,i. | (3.6) |
Let ∑Nj=1aij+1=di, then (3.6) can be written as
˙V1,i=z1,i[di(fi(x2,i)−Ci+∑nj=1aijx2,jNjqmax,i)−˙qref−n∑j=1,j≠iaij(fj(x2,j)−Cj+∑nk=1ajkx2,kNkqmax,j+ωj(t))+diωi(t)]−1r1˜θ1,i˙ˆθ1,i. | (3.7) |
The following nonlinear functions are approximated by FLS. According to Lemma 1, there are fuzzy logic functions ΦT1,iξ1,i(X) that satisfy
F1,i(X)=−n∑j=1,j≠iaij(fj(x2,j)−Cj+∑nk=1ajkx2,kNkqmax,j+ωj(t))+diωi(t)=ΦT1,iξ1,i(X)+ϵ1,i(X),ϵ1,i(X)≤ε1,i. |
From young's inequality of Lemma 2
z1,iF1,i(X)=z1,iΦT1,iξ1,i(X)+z1,iϵ1,i(X)≤12a21z21,iθ1,iξT1,iξ1,i+12a21+12z21,i+12ε21,i. |
Therefore, (3.7) can be reformulated as
˙V1,i≤z1,i[di(fi(x2,i)−Ci+∑nj=1aijx2,jNjqmax,i)−˙qref]+12a21z21,iθ1,iξT1,iξ1,i+12a21+12z21,i+12ε21,i−1r1˜θ1,i˙ˆθ1,i. | (3.8) |
According to the (3.3), we have
1r1˜θ1,i˙ˆθ1,i=12a21z21,i˜θ1,iξT1,iξ1,i−τ1,ir1˜θ1,iˆθ1,i. |
It is noted that
τ1,ir1˜θ1,iˆθ1,i≤−τ1,i2r1˜θ21,i+τ1,i2r1θ21,i. |
Due to z2,i=x2,i−α1,i⇒x2,i=z2,i+α1,i. Substituting (3.2) into (3.8), the calculation of V1,i can be determined as:
˙V1,i≤diRqmax,iz1,iz2,i+12a21+12z21,i+12ε21,i−τ1,i2r1˜θ21,i+τ1,i2r1θ21,i. | (3.9) |
Step 2. Consider the following Lyapunov function:
V2,i=V1,i+12z22,i+12r2˜θ22,i. | (3.10) |
The computation of the derivative of V2,i is expressed as follows:
˙V2,i=˙V1,i+z2,i[gσ(t),i(x2,i)+hσ(t),i(x2,i)sat(D(ui))−˙α1,i]−1r2˜θ2,i˙ˆθ2,i. | (3.11) |
Define the following control laws:
ui={u′iˆθ2,i+ur,i,z2,i<0−u′iˆθ2,i+ul,i,z2,i≥0 | (3.12) |
where u′i≥0, θ2,i=hσ(t),iηimi and mi=min{mr,i,ml,i}.
We'll delve into the discussion of the following two cases:
Case 1:z2,i<0
Since z2,i<0, It follows from (3.12) that one has
ui=u′iˆθ2,i+ur,i. |
Since ui>ur,i, from (2.4), one has
D(u)=mr,i(ui−ur,i). |
For the analysis of sat(D(ui)), we have the following two cases:
(1) ui≤umax,imr,i+ur,i
From (2.7), it gives
sat(D(ui))=mr,i(ui−ur,i). | (3.13) |
According to Lemma 3 and combine (3.12) and (3.13), we have
z2,ihσ(t),isat(D(ui))≤z2,ibmr,i(ui−ur,i)=z2,ibmr,iu′iˆθ2,i. | (3.14) |
This case is based on z2,i<0 discussion, one has z2,i=−|z2,i|. Then, (3.14) can be rewritten as
z2,ihσ(t),isat(D(ui))≤z2,ibmr,iu′iˆθ2,i≤−|z2,i|ηibmr,iu′iˆθ2,i | (3.15) |
where 0<ηi≤℘(D(ui))≤1.
Substituting (3.15) into (3.11) yields
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibmr,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.16) |
(2) ui>umax,imr,i+ur,i
From (2.7), it gives
sat(D(ui))=umax,iD(ui)D(ui)=℘(D(ui))mr,i(ui−ur,i). | (3.17) |
According to Lemma 3 and combine (3.12), (3.17), we have
z2,ihσ(t),isat(D(ui))≤z2,ib℘(D(ui))mr,i(ui−ur,i)=z2,ib℘(D(ui))mr,iu′iˆθ2,i. | (3.18) |
Since 0<ηi<℘(D(ui))≤1, similar to (3.15), we have
z2,ihσ(t),isat(D(ui))≤−|z2,i|bηimr,iu′iˆθ2,i. | (3.19) |
Substituting (3.19) into (3.11) yields
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibmr,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.20) |
Based on the above discussion of (1) and (2), in Case 1, when subjected to the control law defined in (3.12), (3.11) can be formulated as
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibmr,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.21) |
Case 2:z2,i≥0
Since z2,i≥0, It follows from (3.12) that one has
ui=−u′iˆθ2,i+ul,i. |
Since ui≤ur,i, from (2.4), one has
D(u)=ml,i(ui−ul,i). |
For the analysis of sat(D(ui)), we have the following two cases:
(1) ui≥−umin,iml,i+ul,i
From (2.7), it gives
sat(D(ui)=ml,i(ui−ul,i). | (3.22) |
According to Lemma 3 and combine (3.12), (3.22), we have
z2,ihσ(t),isat(D(ui))≤z2,ibml,i(ui−ul,i)=z2,ibml,iu′iˆθ2,i. | (3.23) |
This case is based on z2,i<0 discussion, one has z2,i=−|z2,i|. Then, (3.23) can be rewritten as
z2,ihσ(t),isat(D(ui))≤z2,ibml,iu′iˆθ2,i≤−|z2,i|ηibml,iu′iˆθ2,i, | (3.24) |
where 0<ηi≤℘(D(ui))≤1.
Substituting (3.24) into (3.11) yields
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibml,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.25) |
(2) ui<−umin,iml,i+ul,i
From (2.7), it gives
sat(D(ui))=umax,iD(ui)D(ui)=℘(D(ui))ml,i(ui−ul,i). | (3.26) |
According to Lemma 3 and combine (3.12), (3.26), we have
z2,ihσ(t),isat(D(ui))≤z2,ib℘(D(ui))ml,i(ui−ul,i)=z2,ib℘(D(ui))ml,iu′iˆθ2,i. | (3.27) |
Since 0<ηi<℘(D(ui))≤1, similar to (3.24), we have
z2,ihσ(t),isat(D(ui))≤−|z2,i|bηiml,iu′iˆθ2,i. | (3.28) |
Substituting (3.28) into (3.11) yields
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibml,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.29) |
Based on the above discussion of (1) and (2), in Case 2, when subjected to the control law defined in (3.12), (3.11) can be formulated as
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|ηibml,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.30) |
Due to θ2,i=hσ(t),iηimi and mi=min{mr,i,ml,i}, the following inequalities are obtained:
−|z2,i|ηibmr,iu′iˆθ2,i≤−|z2,i|θ2,iu′iˆθ2,i−|z2,i|ηibml,iu′iˆθ2,i≤−|z2,i|θ2,iu′iˆθ2,i. |
Therefore, according to the discussions in Cases 1 and 2, from (3.20) and (3.29), we have
˙V2,i≤˙V1,i+z2,igσ(t),i(x2,i)−|z2,i|θ2,iu′iˆθ2,i−z2,i˙α1,i−1r2˜θ2,i˙ˆθ2,i. | (3.31) |
According to Lemma 1, we can approximate the unknown function F2,i(X) using fuzzy logic functions ΦT2,iξ2,i(X). Similarly, one easily obtains
−z2,i˙α1,i≤12a22z22,iθ2,iξT2,iξ2,i+12a22+12z22,i+12ε22,i. | (3.32) |
Following a procedure akin to Step 1, we can derive the subsequent inequality:
1r2˜θ2,i˙ˆθ2,i=12a22z22,i˜θ2,iξT2,iξ2,i−τ2,ir2˜θ2,iˆθ2,iτ2,ir2˜θ2,iˆθ2,i≤−τ2,i2r2,i˜θ22,i+τ2,i2r2θ22,i. | (3.33) |
It follows from the young's inequality that we have
z2,igσ(t),i=z2,iNσ(t),iR≤z22,iN2σ(t),i2R2+12. | (3.34) |
Applying (3.32)–(3.34), we have
˙V2,i≤˙V1,i−|z2,i|θ2,iu′iˆθ2,i+12z22,i(Nσ(t),iR)2+12a22z22,iθ2,iξT2,iξ2,i−12a22z22,i˜θ2,iξT2,iξ2,i+12a22+12z22,i+12ε22,i+12−τ2,i2r2˜θ22,i+τ2,i2r2θ22,i. | (3.35) |
Now, u′i in control law ui can be defined by
u′i=1θ2,iˆθ2,i[12(diRqmax,i)2z21,iz2,i+12z2,i(Nσ(t),iR)2−12a22z2,iˆθ2,iξT2,iξ2,i]. | (3.36) |
Substituting (3.9) and (3.36) into (3.35) yields
˙V2,i≤12z21,i+12a21+12ε21,i−τ1,i2r1˜θ21,i+τ1,i2r1θ21,i+12z22,i+12a22+12ε22,i−τ2,i2r2˜θ22,i+τ2,i2r2θ22,i≤KiV2,i+△i | (3.37) |
where Ki=min{1,−τ1,i,−τ2,i}, △i=∑2j=1(12a2j+12ε2j,i+τj,i2rjθ2j,i).
Consider the following Lyapunov function:
V=n∑i=1V2,i. | (3.38) |
Substitute V2,i, the derivative of (3.38) can be given by
˙V≤KV+△ | (3.39) |
where K=∑ni=1Ki, △=∑ni=1△i.
Obviously, V satisfies the following inequality
0≤V≤e−KtV(0)+△K. | (3.40) |
It is readily apparent from (3.40) that V is bounded. The demonstration of Theorem 1 is now concluded.
This chapter simulates the proposed AQM network congestion control algorithm and evaluates the efficiency and superiority of the controller. A multi-bottleneck network featuring three bottlenecks is examined, and its topology is illustrated in Figure 1. Matlab is used to simulate the presented method, the parameters of the TCP/AQM network system are set as follows:
c1,1=3;c1,2=3;c1,3=3;c2,1=15000;c2,2=9000;c2,3=9000;a1=1;a2=5;r1=1;r2=0.003;d1=1;d2=2;d3=2;R=0.08;N1=85;N2=85;N3=80;C=3500;qref=0.25;qmax,1=730;qmax,2=750;qmax,3=720;ω=cos(t). |
The initial state of the system is x0=[0.205,1,0.205,1,0.205,1,1,1,1,1, 1,1,1], and the results of the simulations are depicted in Figures 2–8.
In Figure 2, the dynamic evolution of the queue length for each node is illustrated. Notably, as the target queue length is set at 180, the queue length for each node converges to a stable state, demonstrating a rapid response and effective control. This underscores the robustness and superiority of the AQM scheme devised in this paper.
Figure 3 showcases the trajectory of the tracking error for each node. As depicted in the Figure 3, the tracking error remains stable, confined within the specified upper and lower bounds, and converges in close proximity to the origin. This observation underscores the superior transient performance of the controller devised in this paper.
In Figure 4, the packet loss probability is introduced, and it is obvious that the packet loss probability is always in p∈[0,1].
Figure 5 represents the variation of the adaptive law. After 1s, the adaptive law tends to be stable and bounded, indicating that the controller formulated in this paper can make good use of the adaptive law for precise estimation of link capacity.
In order to verify the effectiveness of the proposed algorithm, the tracking error and queue length are compared respectively. The comparison results are shown in Figures 6–11. The comparison objects are the proposed algorithm, single bottleneck network (different topographs)[31], EO-PID[39], PSO-PID, and RED.
In Figures 6-8, obviously, the single-bottleneck network and the multi-bottleneck network in this paper are the most stable in the experimental results. The single-bottleneck network tends to be stable at 0.88s, while the multi-bottleneck network in this paper tends to be stable at 1.56s. However, it is worth noting that the queue length of the multi-bottleneck network in this paper is 2.5 times that of the single bottleneck, so the multi-bottleneck network in this paper is more suitable for actual congestion control.
In Figures 6–8, the tracking error of the five algorithms tends to 0 stably, but EO-PID and PSO-PID have obvious jitter, while the tracking error of RED is stable but larger than that of other algorithms. Compared with other algorithms, the tracking error of the multi-bottleneck network and the single-bottleneck network in this paper is the most stable and the smallest. Careful comparison shows that the multi-bottleneck network in this paper is superior to the single-bottleneck network. It shows that the multi-bottleneck AQM algorithm in this paper has good robustness.
In this paper, a novel adaptive congestion control algorithm is developed specifically for multi-bottleneck TCP/AQM network system, considering both dead zone and saturated input interference for the first time. Combined with the approximation characteristics of the FLS and the backstepping technology, the algorithm regards the multi-bottleneck network as a cohesive entity. The adaptive fuzzy controller enhances the robustness of individual nodes within the multi-bottleneck network, and all the network nodes can track the required queue length according to different queue capacity. Finally, through simulation, the feasibility of the designed AQM network congestion control algorithm is verified.
The authors declare they have not used Artificial Intelligence (AI) tools in the creation of this article.
This project is funded by the National Natural Science Foundation of China, No. 61932005.
The authors have declared no conflicts of interest.
[1] |
A. K. Chakraborty, A. Kosmrlj, Statistical mechanical concepts in immunology, Annu. Rev. Phys. Chem., 61 (2010), 283–303. https://doi.org/10.1146/annurev.physchem.59.032607.093537 doi: 10.1146/annurev.physchem.59.032607.093537
![]() |
[2] |
P. Nieuwenhuis, D. Opstelten, Functional anatomy of germinal centers, Dev. Dynam., 170 (1984), 421–435. https://doi.org/10.1002/aja.1001700315 doi: 10.1002/aja.1001700315
![]() |
[3] |
D. M. Tarlinton, K. G. C. Smith, Dissecting affinity maturation: a model explaining selection of antibody-forming cells and memory b cells in the germinal centre, Immunol. Today, 21 (2000), 436–441. https://doi.org/10.1016/S0167-5699(00)01687-X doi: 10.1016/S0167-5699(00)01687-X
![]() |
[4] | I. C. Maclennan, Germinal centers, Annu. Rev. Immunol., 12 (1994), 117–139. https://doi.org/10.1146/annurev.immunol.12.1.117 |
[5] |
T. A. Schwickert, R. L. Lindquist, G. Shakhar, G. Livshits, M. C. Nussenzweig, in vivo imaging of germinal centres reveals a dynamic open structure, Nature, 446 (2007), 83–87. https://doi.org/10.1038/nature05573 doi: 10.1038/nature05573
![]() |
[6] |
Y. Natkunam, The biology of the germinal center, Hematology, 2007 (2007), 210–215. https://doi.org/10.1182/asheducation-2007.1.210 doi: 10.1182/asheducation-2007.1.210
![]() |
[7] |
C. D. C. Allen, T. Okada, H. Tang, J. G. Cyster, Imaging of germinal center selection events during affinity maturation, Science, 315 (2007), 528–531. https://doi.org/10.1126/science.1136736 doi: 10.1126/science.1136736
![]() |
[8] | G. D. Victora, M. C. Nussenzweig, Germinal centers, Annu. Rev. Immunol., 30 (2012), 429–457. https://doi.org/10.1146/annurev-immunol-020711-075032 |
[9] |
A. S. Perelson, G. F. Oster, Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination, J. Theor. Biol., 81 (1979), 645–670. https://doi.org/10.1016/0022-5193(79)90275-3 doi: 10.1016/0022-5193(79)90275-3
![]() |
[10] |
T. B. Kepler, A. S. Perelson, Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation, Immunol. Today, 14 (1993), 412–415. https://doi.org/10.1016/0167-5699(93)90145-B doi: 10.1016/0167-5699(93)90145-B
![]() |
[11] |
A. S. Perelson, G. Weisbuch, Immunology for physicists, Rev. Mod. Phys., 69 (1997), 1219–1267. https://doi.org/10.1103/RevModPhys.69.1219 doi: 10.1103/RevModPhys.69.1219
![]() |
[12] |
M. Oprea, Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts, J. Immunol., 158(1997), 5155–5162. https://doi.org/10.1016/S0165-2478(97)85162-0 doi: 10.1016/S0165-2478(97)85162-0
![]() |
[13] |
S. Erwin, S. M. Ciupe, Germinal center dynamics during acute and chronic infection, Math. Biosci. Eng., 14 (2017), 655–671. https://doi.org/10.3934/mbe.2017037 doi: 10.3934/mbe.2017037
![]() |
[14] |
M. Meyer-Hermann, M. T. Figge, K. M. Toellner, Germinal centres seen through the mathematical eye: B-cell models on the catwalk, Trends Immunol., 30 (2009), 157–164. https://doi.org/10.1016/j.it.2009.01.005 doi: 10.1016/j.it.2009.01.005
![]() |
[15] |
L. Buchauer, H. Wardemann, Calculating germinal centre reactions, Curr. Opin. Syst. Biol., 18 (2019), 1–8. https://doi.org/10.1016/j.coisb.2019.10.004 doi: 10.1016/j.coisb.2019.10.004
![]() |
[16] |
M. J. Shlomchik, F. Weisel, Germinal center selection and the development of memory B and plasma cells, Immunol. Rev., 247 (2012), 52–63. https://doi.org/10.1111/j.1600-065X.2012.01124.x doi: 10.1111/j.1600-065X.2012.01124.x
![]() |
[17] |
M. Meyer-Hermann, P. K. Maini, Interpreting two-photon imaging data of lymphocyte motility, Phys. Rev. E, 71 (2005), 061912. https://doi.org/10.1103/PhysRevE.71.061912 doi: 10.1103/PhysRevE.71.061912
![]() |
[18] |
M. T. Figge, A. Garin, M. Gunzer, M. Kosco-Vilbois, K. M. Toellner, M. Meyer-Hermann, Deriving a germinal center lymphocyte migration model from two-photon data, J. Exp. Med., 205 (2008), 3019–3029. https://doi.org/10.1084/jem.20081160 doi: 10.1084/jem.20081160
![]() |
[19] |
T. Beyer, M. Meyer-Hermann, G. Soff, A possible role of chemotaxis in germinal center formation, Int. Immunol., 14 (2003), 1369–1381. https://doi.org/10.1016/j.celrep.2012.05.010 doi: 10.1016/j.celrep.2012.05.010
![]() |
[20] |
M. Meyer-Hermann, A mathematical model for the germinal center morphology and affinity maturation, J. Theor. Biol., 216 (2002), 273–300. https://doi.org/10.1016/j.coisb.2019.10.004 doi: 10.1016/j.coisb.2019.10.004
![]() |
[21] |
M. Meyer-Hermann, A concerted action of b cell selection mechanisms, Adv. Complex. Syst., 10 (2007), 557–580. https://doi.org/10.1142/S0219525907001276 doi: 10.1142/S0219525907001276
![]() |
[22] |
S. Crotty, T follicular helper cell biology: A decade of discovery and diseases, Immunity, 50 (2019), 1132–1148. https://doi.org/10.1016/j.immuni.2019.04.011 doi: 10.1016/j.immuni.2019.04.011
![]() |
[23] |
M. Meyer-Hermann, P. K. Maini, A. D. Iber, An analysis of B cell selection mechanisms in germinal centres, Math. Med. Biol., 23 (2006), 255–277. https://doi.org/10.1007/s11538-009-9408-8 doi: 10.1007/s11538-009-9408-8
![]() |
[24] | M. J. Thomas, U. Klein, J. Lygeros, M. R. Martínez, A probabilistic model of the germinal center reaction, Front. Immunol., 10 (2019). https://doi.org/10.3389/fimmu.2019.00689 |
[25] |
M. Meyer-Hermann, E. Mohr, N. Pelletier, Y. Zhang, G. D. Victora, K. M. Toellner, A theory of germinal center B cell selection, division, and exit, Cell Rep., 2 (2012), 162–174. https://doi.org/10.1016/j.celrep.2012.05.010 doi: 10.1016/j.celrep.2012.05.010
![]() |
[26] |
P. A. Robert, A. L. Marschall, M. Meyer-Hermann, Induction of broadly neutralizing antibodies in germinal centre simulations, Curr. Opin. Biotechnol., 51 (2018), 137–145. https://doi.org/10.1016/j.copbio.2018.01.006 doi: 10.1016/j.copbio.2018.01.006
![]() |
[27] | M. Molari, K. Eyer, J. Baudry, S. Cocco, R. Monasson, Quantitative modeling of the effect of antigen dosage on b-cell affinity distributions in maturating germinal centers, Elife, 9 (2020). https://doi.org/10.7554/elife.55678 |
[28] | E. M. Tejero, D. Lashgari, R. García-Valiente, X. Gao, F. Crauste, P. A. Robert, et al., Multiscale modeling of germinal center recapitulates the temporal transition from memory B cells to plasma cells differentiation as regulated by antigen affinity-based tfh cell help, Front. Immunol., 11 (2021). https://doi.org/10.3389/fimmu.2020.620716 |
[29] |
S. Wang, J. Mata-Fink, B. Kriegsman, M. Hanson, D. Irvine, H. Eisen, et al., Manipulating the selection forces during affinity maturation to generate cross-reactive hiv antibodies, Cell, 160 (2015), 785–797. https://doi.org/10.1016/j.cell.2015.01.027 doi: 10.1016/j.cell.2015.01.027
![]() |
[30] |
N. Wittenbrink, T. S. Weber, A. Klein, A. A. Weiser, W. Zuschratter, M. Sibila, et al., Broad volume distributions indicate nonsynchronized growth and suggest sudden collapses of germinal center B cell populations, J. Immunol., 184 (2010), 1339–1347. https://doi.org/10.4049/jimmunol.0901040 doi: 10.4049/jimmunol.0901040
![]() |
[31] |
N. Wittenbrink, A. Klein, A. A. Weiser, J. Schuchhardt, M. Or-Guil, Is there a typical germinal center? a large-scale immunohistological study on the cellular composition of germinal centers during the hapten-carrier-driven primary immune response in mice, J. Immunol., 187 (2011), 6185–6196. https://doi.org/10.4049/jimmunol.1101440 doi: 10.4049/jimmunol.1101440
![]() |
[32] |
P. Wang, C. M. Shih, H. Qi, Y. H. Lan, A stochastic model of the germinal center integrating local antigen competition, individualistic T-B interactions, and B cell receptor signaling, J. Immunol., 197 (2016), 1169–1182. https://doi.org/10.4049/jimmunol.1600411 doi: 10.4049/jimmunol.1600411
![]() |
[33] |
D. T. Gillespie, Exact stochastic simulation of coupled chemical-reactions, J. Phys. Chem., 81 (1977), 2340–2361. https://doi.org/10.1021/j100540a008 doi: 10.1021/j100540a008
![]() |
[34] |
A. D. Gitlin, C. T. Mayer, T. Y. Oliveira, Z. Shulman, M. J. K. Jones, A. Koren, et al., T cell help controls the speed of the cell cycle in germinal center B cells, Science, 349 (2015), 643–646. https://doi.org/10.1126/science.aac4919 doi: 10.1126/science.aac4919
![]() |
[35] |
H. Qi, J. G. Egen, A. Y. C. Huang, R. N. Germain, Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells, Science, 312 (2006), 1672–1676. https://doi.org/10.1126/science.1125703 doi: 10.1126/science.1125703
![]() |
[36] |
H. Qi, J. L. Cannons, F. Klauschen, P. L. Schwartzberg, R. N. Germain, Sap-controlled T-B cell interactions underlie germinal centre formation, Nature, 455 (2008), 764–769. https://doi.org/10.1038/nature07345 doi: 10.1038/nature07345
![]() |
[37] |
J. G. Cyster, Chemokines and cell migration in secondary lymphoid organs, Science, 286 (1999), 2098–2102. https://doi.org/10.1126/science.286.5447.2098 doi: 10.1126/science.286.5447.2098
![]() |
[38] |
H. Qi, X. Chen, C. Chu, P. Lu, H. Xu, J. Yan, Follicular t-helper cells: controlled localization and cellular interactions, Immunol. Cell Biol., 92 (2014), 28–33. https://doi.org/10.1038/icb.2013.59 doi: 10.1038/icb.2013.59
![]() |
[39] |
H. Qi, W Kastenmüller, R. N. Germain, Spatiotemporal basis of innate and adaptive immunity in secondary lymphoid tissue, Annu. Rev. Cell Dev. Biol., 30 (2014), 141–167. https://doi.org/10.1146/annurev-cellbio-100913-013254 doi: 10.1146/annurev-cellbio-100913-013254
![]() |
[40] |
Z. Shulman, A. D. Gitlin, S. Targ, M. Jankovic, G. Pasqual, M. C. Nussenzweig, et al., T follicular helper cell dynamics in germinal centers, Science, 341 (2013), 673–677. https://doi.org/10.1126/science.1241680 doi: 10.1126/science.1241680
![]() |
[41] |
J. S. Shaffer, P. L. Moore, M. Kardar, A. K. Chakraborty, Optimal immunization cocktails can promote induction of broadly neutralizing abs against highly mutable pathogens, PNAS, 113 (2016), 7039–7048. https://doi.org/10.1073/pnas.1614940113 doi: 10.1073/pnas.1614940113
![]() |
[42] |
B. J. C. Quah, V. P. Barlow, V. Mcphun, K. I. Matthaei, M. D. Hulett, C. R. Parish, Bystander B cells rapidly acquire antigen receptors from activated B cells by membrane transfer, PNAS, 105 (2008), 4259–4264. https://doi.org/10.1073/pnas.0800259105 doi: 10.1073/pnas.0800259105
![]() |
[43] |
O. Bannard, R. Horton, C. C. Allen, J. An, T. Nagasawa, J. Cyster, Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection, Immunity, 39 (2013), 1182. https://doi.org/10.1016/j.immuni.2013.11.006 doi: 10.1016/j.immuni.2013.11.006
![]() |
[44] |
D. Liu, H. Xu, C. M. Shih, Z. Wan, X. P. Ma, W. Ma et al., T–B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction, Nature, 517 (2015), 214–218. https://doi.org/10.1038/nature13803 doi: 10.1038/nature13803
![]() |
[45] |
J. Shi, S. Hou, Q. Fang, X. Liu, X. Liu, H. Qi, Pd-1 controls follicular t helper cell positioning and function, Immunity, 49 (2018), 264–274. https://doi.org/10.1016/j.immuni.2018.06.012 doi: 10.1016/j.immuni.2018.06.012
![]() |
[46] |
J. Jacob, R. Ksssir, G. Kelsoe, In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl) acetyl. I. the architecture and dynamics of responding cell populations, J. Exp. Med., 173 (1991), 1165–1175. https://doi.org/10.1084/jem.173.5.1165 doi: 10.1084/jem.173.5.1165
![]() |
[47] |
F. Kroese, A. S. Wubbena, H. G. Seijen, P. Nieuwenhuis, Germinal centers develop oligoclonally, Eur. J. Immunol., 17 (1987), 1069–1072. https://doi.org/10.1002/eji.1830170726 doi: 10.1002/eji.1830170726
![]() |
[48] |
A. Lapedes, R. Farber, The geometry of shape space: application to influenza, J. Theor. Biol., 212 (2001), 57–69. https://doi.org/10.1006/jtbi.2001.2347 doi: 10.1006/jtbi.2001.2347
![]() |
[49] |
G. Kelsoe, The germinal center: a crucible for lymphocyte selection, Semin. Immunol., 8 (1996), 179–184. https://doi.org/10.1006/smim.1996.0022 doi: 10.1006/smim.1996.0022
![]() |
[50] |
M. J. Miller, S. H. Wei, I. Parker, M. D. Cahalan, Two-photon imaging of lymphocyte motility and antigen response in intact lymph node, Science, 296 (2002), 1869–1873. https://doi.org/10.1126/science.1070051 doi: 10.1126/science.1070051
![]() |
[51] |
S. H. Wei, I. Parker, M. J. Miller, M. D. Cahalan, A stochastic view of lymphocyte motility and trafficking within the lymph node, Immunol. Rev., 195 (2003), 136–159. https://doi.org/10.1034/j.1600-065x.2003.00076.x doi: 10.1034/j.1600-065x.2003.00076.x
![]() |
[52] |
Y. J. Liu, J. Zhang, P. J. L. Lane, Y. T. Chan, I. C. M. Maclennan, Sites of specific B cell activation in primary and secondary responses to T cell-dependent and T cell-independent antigens, Eur. J. Immunol., 21 (1991), 2951–2962. https://doi.org/10.1002/eji.1830211209 doi: 10.1002/eji.1830211209
![]() |
[53] |
S. Han, In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl) acetyl. IV. affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self-tolerance, J. Exp. Med., 182 (1995), 1635–1644. https://doi.org/10.1084/jem.173.5.1165 doi: 10.1084/jem.173.5.1165
![]() |
[54] |
C. D. C. Allen, T. Okada, J. G. Cyster, Germinal center organization and cellular dynamics, Immunity, 27 (2007), 190–202. https://doi.org/10.1016/j.immuni.2007.07.009 doi: 10.1016/j.immuni.2007.07.009
![]() |
[55] |
S. A. Camacho, M. H. Kosco-Vilbois, C. Berek, The dynamic structure of the germinal center, Immunol. Today, 19 (1998), 511–514. https://doi.org/10.1016/S0167-5699(98)01327-9 doi: 10.1016/S0167-5699(98)01327-9
![]() |
[56] |
N. S. De Silva, U. Klein, Dynamics of B cells in germinal centres, Nat. Rev. Immunol., 15 (2015), 137–148. https://doi.org/10.1038/nri3804 doi: 10.1038/nri3804
![]() |
[57] | C. T. Mayer, A. Gazumyan, E. E. Kara, A. D. Gitlin, J. Golijanin, C. Viant, et al., The microanatomic segregation of selection by apoptosis in the germinal center, Science, 358 (2017). https://doi.org/10.1126/science.aao2602 |
[58] |
J. M. J. Tas, L. Mesin, G. Pasqual, S. Targ, J. T. Jacobsen, Y. M. Mano, et al., Visualizing antibody affinity maturation in germinal centers, Science, 351 (2016), 1048–1054. https://doi.org/10.1126/science.aad3439 doi: 10.1126/science.aad3439
![]() |
[59] | R. Murugan, L. Buchauer, G. Triller, C. Kreschel, H. Wardemann, Clonal selection drives protective memory B cell responses in controlled human malaria infection, Sci. Immunol., 3 (2018). https://doi.org/10.1126/sciimmunol.aap8029 |
[60] | K. Kwak, N. Quizon, H. Sohn, A. Saniee, J. Manzella-Lapeira, P. Holla, et al., Intrinsic properties of human germinal center B cells set antigen affinity thresholds, Sci. Immunol., 3 (2018). https://doi.org/10.1126/sciimmunol.aau6598 |
[61] |
T. A. Schwickert, G. D. Victora, D. R. Fooksman, A. O. Kamphorst, M. R. Mugnier, A. D. Gitlin, et al., A dynamic t cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center, J. Exp. Med., 208 (2011), 1243–1252. https://doi.org/10.1084/jem.20102477 doi: 10.1084/jem.20102477
![]() |
[62] |
M. Meyer-Hermann, T. Beyer, Conclusions from two model concepts on germinal center dynamics and morphology, Dev. immunol., 9 (2002), 203–214. https://doi.org/10.1080/1044-6670310001597060 doi: 10.1080/1044-6670310001597060
![]() |
[63] |
P. A. Robert, T Arulraj, M. Meyer-Hermann, Ymir: A 3d structural affinity model for multi-epitope vaccine simulations, IScience, 24 (2021), 102979. https://doi.org/10.1016/j.isci.2021.102979 doi: 10.1016/j.isci.2021.102979
![]() |
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