There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Machine Learning is the study of methods for programming computers to learn. Computers are applied to a wide range of tasks, and for most of these it is relatively easy for programmers to design and implement the necessary software. However, there are many tasks for which this is difficult or impossible. These can be divided into four general categories. First, there are problems for which there exist no human experts. For example, in modern automated manufacturing facilities, there is a need to predict machine failures before they occur by analyzing sensor readings. Because the machines are new, there are no human experts who can be interviewed by a programmer to provide the knowledge necessary to build a computer system. A machine learning system can study recorded data and subsequent machine failures and learn prediction rules. Second, there are problems where human experts exist, but where they are unable to explain their expertise. This is the case in many perceptual tasks, such as speech recognition, hand-writing recognition, and natural language understanding. Virtually all humans exhibit expert-level abilities on these tasks, but none of them can describe the detailed steps that they follow as they perform them. Fortunately, humans can provide machines with examples of the inputs and correct outputs for these tasks, so machine learning algorithms can learn to map the inputs to the outputs. Third, there are problems where phenomena are changing rapidly. In finance, for example, people would like to predict the future behavior of the stock market, of consumer purchases, or of exchange rates. These behaviors change frequently, so that even if a programmer could construct a good predictive computer program, it would need to be rewritten frequently. A learning program can relieve the programmer of this burden by constantly modifying and tuning a set of learned prediction rules. Fourth, there are applications that need to be customized for each computer user separately. Consider, for example, a program to filter unwanted electronic mail messages. Different users will need different filters. It is unreasonable to expect each user to program his or her own rules, and it is infeasible to provide every user with a software engineer to keep the rules up-to-date. A machine learning system can learn which mail messages the user rejects and maintain the filtering rules automatically. Machine learning addresses many of the same research questions as the fields of statistics, data mining, and psychology, but with differences of emphasis. Statistics focuses on understanding the phenomena that have generated the data, often with the goal of testing different hypotheses about those phenomena. Data mining seeks to find patterns in the data that are understandable by people. Psychological studies of human learning aspire to understand the mechanisms underlying the various learning behaviors exhibited by people (concept learning, skill acquisition, strategy change, etc.).

Machine learning

In this paper, we discuss consensus problems for networks of dynamic agents with fixed and switching topologies. We analyze three cases: 1) directed networks with fixed topology; 2) directed networks with switching topology; and 3) undirected networks with communication time-delays and fixed topology. We introduce two consensus protocols for networks with and without time-delays and provide a convergence analysis in all three cases. We establish a direct connection between the algebraic connectivity (or Fiedler eigenvalue) of the network and the performance (or negotiation speed) of a linear consensus protocol. This required the generalization of the notion of algebraic connectivity of undirected graphs to digraphs. It turns out that balanced digraphs play a key role in addressing average-consensus problems. We introduce disagreement functions for convergence analysis of consensus protocols. A disagreement function is a Lyapunov function for the disagreement network dynamics. We proposed a simple disagreement function that is a common Lyapunov function for the disagreement dynamics of a directed network with switching topology. A distinctive feature of this work is to address consensus problems for networks with directed information flow. We provide analytical tools that rely on algebraic graph theory, matrix theory, and control theory. Simulations are provided that demonstrate the effectiveness of our theoretical results.

/pdf/consensus-problems-in-networks-of-agents-with-switching-25c3hqvtd8.pdf

Consensus problems in networks of agents with switching topology and time-delays

Single-cell bacterial sensors have numerous applications in human health monitoring, environmental chemical detection, and materials biosynthesis. Such bacterial devices need not only the capability to differentiate between combinations of inputs, but also the ability to process signal timing and duration. In this work, we present a two-input temporal logic gate that can sense and record the order of the inputs, the timing between inputs, and the duration of input pulses. The temporal logic gate design relies on unidirectional DNA recombination with bacteriophage integrases to detect and encode sequences of input events. When implemented in a chromosomally-modified E. coli strain, we can utilize stochastic single cell responses to predict overall heterogeneous population behavior. We show that a stochastic model can be used to predict final population distributions of this E. coli strain, and thus that final differentiated sub populations can be used to deduce the timing and duration of transient chemical events.

https://www.biorxiv.org/content/biorxiv/early/2015/10/27/029967.full.pdf

A population-based temporal logic gate for timing and recording chemical events

On a stochastic algorithm for sensor scheduling

The fact that genes compete for shared cellular resources poses a fundamental challenge when identifying parameters of genetic parts. A recently developed model of gene expression tackles this problem by explicitly accounting for resource competition. In addition to accurately describing experimental data, this model only depends on a small number of easily identifiable parameters with clear physical interpretation. Based on this model, we outline a procedure to select the optimal set of experiments to characterize biomolecular parts in synthetic biology. Additionally, we reveal the role competition for shared resources plays, provide guidelines how to minimize its detrimental effects, and how to leverage this phenomenon to extract the most information about unknown parameters. To illustrate the results, we consider the case of part characterization in cell-free extracts, treat plasmid DNA concentrations as decision variables, and demonstrate the significant performance difference between naive and optimal experiment design.

/pdf/optimal-experiment-design-and-leveraging-competition-for-30yeamgidn.pdf

Optimal Experiment Design and Leveraging Competition for Shared Resources in Cell-Free Extracts

The control programs of complex autonomous systems that have conditional branching can be modeled as linear hybrid systems. When the state knowledge is perfect, linear hybrid systems with state- based transition conditions can be verified against a specified unsafe set using existing model checking software. This paper introduces a formal method for calculating the failure probability due to state estimation uncertainty of these sensor-driven hybrid systems. Problem complexity is described and some reduction techniques for the failure probability calculation are given. An example goal-based control program is given and the failure probability for that system is calculated.

Probabilistic Safety Analysis of Sensor-Driven Hybrid Automata

It has been an ongoing scientific debate whether biological parameters are conserved across experimental setups with different media, pH values, and other experimental conditions. Our work explores this question using Bayesian probability as a rigorous framework to assess the biological context of parameters in a model of the cell growth controller in You et al. When this growth controller is uninduced, the E. coli cell population grows to carrying capacity; however, when the circuit is induced, the cell population growth is regulated to remain well below carrying capacity. This growth control controller regulates the E. coli cell population by cell to cell communication using the signaling molecule AHL and by cell death using the bacterial toxin CcdB. 

To evaluate the context dependence of parameters such as the cell growth rate, the carrying capacity, the AHL degradation rate, the leakiness of AHL, the leakiness of toxin CcdB, and the IPTG induction factor, we collect experimental data from the growth control circuit in two different media, at two different pH values, and with several induction levels. We define a set of possible context dependencies that describe how these parameters may differ with the experimental conditions and we develop mathematical models of the growth controller across the different experimental contexts. We then determine whether these parameters are shared across experimental contexts or whether they are context dependent. For each of these possible context dependencies, we use Bayesian inference to assess its plausibility and to estimate the parameters of the growth controller. Ultimately, we find that there is significant experimental context dependence in this circuit. Moreover, we also find that the estimated parameter values are sensitive to our assumption of a context relationship.

/pdf/context-dependence-of-biological-circuits-ijqlzepq21.pdf

Richard M. Murray

Papers

A population-based temporal logic gate for timing and recording chemical events

On a stochastic algorithm for sensor scheduling

Optimal Experiment Design and Leveraging Competition for Shared Resources in Cell-Free Extracts

Probabilistic Safety Analysis of Sensor-Driven Hybrid Automata

Context Dependence of Biological Circuits