In order to identify the infected individuals of a population, their samples are divided in equally sized groups called pools and a single laboratory test is applied to each pool. Individuals whose samples belong to pools that test negative are declared healthy, while each pool that tests positive is divided into smaller, equally sized pools which are tested in the next stage. In the$(k+1)$-th stage all remaining samples are tested. If$p< 1-3^{-1/3}$, we minimize the expected number of tests per individual as a function of the number$k+1$of stages, and of the pool sizes in the first$k$stages. We show that for each$p\in (0, 1-3^{-1/3})$the optimal choice is one of four possible schemes, which are explicitly described. We conjecture that for each$p$, the optimal choice is one of the two sequences of pool sizes$(3^{k} \text {or }3^{k-1}4,3^{k-1}, {\dots },3^{2},3)$, with a precise description of the range of$p$’s where each is optimal. The conjecture is supported by overwhelming numerical evidence for$p>2^{-51}$. We also show that the cost of the best among the schemes$(3^{k}, {\dots },3)$is of order$O\big (p\log (1/p)\big)$, comparable to the information theoretical lower bound$p\log _{2}(1/p)+(1-p)\log _{2}(1/(1-p))$, the entropy of a Bernoulli$(p)$random variable.

Many natural systems, especially biological ones, exhibit complex multivariate nonlinear dynamical behaviors that can be hard to capture by linear autoregressive models. On the other hand, generic nonlinear models such as deep recurrent neural networks often require large amounts of training data, not always available in domains such as brain imaging; also, they often lack interpretability. Domain knowledge about the types of dynamics typically observed in such systems, such as a certain type of dynamical systems models, could complement purely data-driven techniques by providing a good prior. In this work, we consider a class of ordinary differential equation (ODE) models known as van der Pol (VDP) oscil lators and evaluate their ability to capture a low-dimensional representation of neural activity measured by different brain imaging modalities, such as calcium imaging (CaI) and fMRI, in different living organisms: larval zebrafish, rat, and human. We develop a novel and efficient approach to the nontrivial problem of parameters estimation for a network of coupled dynamical systems from multivariate data and demonstrate that the resulting VDP models are both accurate and interpretable, as VDP's coupling matrix reveals anatomically meaningful excitatory and inhibitory interactions across different brain subsystems. VDP outperforms linear autoregressive models (VAR) in terms of both the data fit accuracy and the quality of insight provided by the coupling matrices and often tends to generalize better to unseen data when predicting future brain activity, being comparable to and sometimes better than the recurrent neural networks (LSTMs). Finally, we demonstrate that our (generative) VDP model can also serve as a data-augmentation tool leading to marked improvements in predictive accuracy of recurrent neural networks. Thus, our work contributes to both basic and applied dimensions of neuroimaging: gaining scientific insights and improving brain-based predictive models, an area of potentially high practical importance in clinical diagnosis and neurotechnology.

The gradient of Bicoid (Bcd) is key for the establishment of the anterior-posterior axis in Drosophila embryos. The gradient properties are compatible with the SDD model in which Bcd is synthesized at the anterior pole and then diffuses into the embryo and is degraded with a characteristic time. Within this model, the Bcd diffusion coefficient is critical to set the timescale of gradient formation. This coefficient has been measured using two optical techniques, Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS), obtaining estimates in which the FCS value is an order of magnitude larger than the FRAP one. This discrepancy raises the following questions: which estimate is "correct''; what is the reason for the disparity; and can the SDD model explain Bcd gradient formation within the experimentally observed times? In this paper, we use a simple biophysical model in which Bcd diffuses and interacts with binding sites to show that both the FRAP and the FCS estimates may be correct and compatible with the observed timescale of gradient formation. The discrepancy arises from the fact that FCS and FRAP report on different effective (concentration dependent) diffusion coefficients, one of which describes the spreading rate of the individual Bcd molecules (the messengers) and the other one that of their concentration (the message). The latter is the one that is more relevant for the gradient establishment and is compatible with its formation within the experimentally observed times.