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

Tree boosting is a highly effective and widely used machine learning method. In this paper, we describe a scalable end-to-end tree boosting system called XGBoost, which is used widely by data scientists to achieve state-of-the-art results on many machine learning challenges. We propose a novel sparsity-aware algorithm for sparse data and weighted quantile sketch for approximate tree learning. More importantly, we provide insights on cache access patterns, data compression and sharding to build a scalable tree boosting system. By combining these insights, XGBoost scales beyond billions of examples using far fewer resources than existing systems.

/pdf/xgboost-a-scalable-tree-boosting-system-48ocu6x4c7.pdf

XGBoost: A Scalable Tree Boosting System

In this paper, we present Google, a prototype of a large-scale search engine which makes heavy use of the structure present in hypertext. Google is designed to crawl and index the Web efficiently and produce much more satisfying search results than existing systems. The prototype with a full text and hyperlink database of at least 24 million pages is available at http://google.stanford.edu/. To engineer a search engine is a challenging task. Search engines index tens to hundreds of millions of web pages involving a comparable number of distinct terms. They answer tens of millions of queries every day. Despite the importance of large-scale search engines on the web, very little academic research has been done on them. Furthermore, due to rapid advance in technology and web proliferation, creating a web search engine today is very different from three years ago. This paper provides an in-depth description of our large-scale web search engine -- the first such detailed public description we know of to date. Apart from the problems of scaling traditional search techniques to data of this magnitude, there are new technical challenges involved with using the additional information present in hypertext to produce better search results. This paper addresses this question of how to build a practical large-scale system which can exploit the additional information present in hypertext. Also we look at the problem of how to effectively deal with uncontrolled hypertext collections where anyone can publish anything they want.

/pdf/the-anatomy-of-a-large-scale-hypertextual-web-search-engine-496poj789d.pdf

The anatomy of a large-scale hypertextual Web search engine

The importance of a Web page is an inherently subjective matter, which depends on the readers interests, knowledge and attitudes. But there is still much that can be said objectively about the relative importance of Web pages. This paper describes PageRank, a mathod for rating Web pages objectively and mechanically, effectively measuring the human interest and attention devoted to them. We compare PageRank to an idealized random Web surfer. We show how to efficiently compute PageRank for large numbers of pages. And, we show how to apply PageRank to search and to user navigation.

The PageRank Citation Ranking : Bringing Order to the Web

Texture synthesis techniques based on matching the Gram matrix of feature activations in neural networks have achieved spectacular success in the image domain. In this paper we extend these techniques to the audio domain. We demonstrate that synthesizing diverse audio textures is challenging, and argue that this is because audio data is relatively low-dimensional. We therefore introduce two new terms to the original Grammian loss: an autocorrelation term that preserves rhythm, and a diversity term that encourages the optimization procedure to synthesize unique textures. We quantitatively study the impact of our design choices on the quality of the synthesized audio by introducing an audio analogue to the Inception loss which we term the VGGish loss. We show that there is a trade-off between the diversity and quality of the synthesized audio using this technique. We additionally perform a number of experiments to qualitatively study how these design choices impact the quality of the synthesized audio. Finally we describe the implications of these results for the problem of audio style transfer.

Synthesizing Diverse, High-Quality Audio Textures.

Aspects of the present disclosure are directed to methods and compositions for the production of heterogeneous tissue from human induced pluripotent stem (hiPS) cells.

Engineering a heterogeneous tissue from pluripotent stem cells

Microrobots have many potential uses in microbiology since they can be remotely actuated and precisely manipulated in biochemical fluids. Cellular function and response depends on biochemicals. Therefore, various delivery methods have been developed for delivering biologically relevant cargo using microrobots. However, localized targeting without payload leakage during transport is challenging. Here, we design a microrobotic platform capable of on-demand delivery of signaling molecules in biological systems. The on-demand delivery method is based on a light-responsive photolabile linker which releases a cell-to-cell signaling molecule when exposed to light, integrated on the surface of microrobots. Successful delivery of the signaling molecules and subsequent gene regulation is also demonstrated. This proposed method can be used for multiple applications, especially in biology, engineering, and medicine where on-demand delivery of chemical cargo at targeted locations is important.

/pdf/cellular-expression-through-morphogen-delivery-by-light-2ns2xxg57u.pdf

Cellular expression through morphogen delivery by light activated magnetic microrobots

Control system theory provides convenient tools and concepts for describing and analyzing complex cell functions. In this paper we demonstrate the use of control theory to forward-engineer a complex synthetic gene network constructed from several modular components. Specifically, we present the design and simulation of a synthetic multi-cellular maze-solving system. Here, bacterial cells are programmed to use artificial cell-to-cell communication and regulatory feedback in order to illuminate the correct path in a user-defined maze of cells arranged on a surface. Simulations were used to analyze the system's spatiotemporal dynamics and sensitivity to various kinetic parameters. Experiments with Escherichia coli were carried out to characterize the diffusion properties of artificial cell-to-cell communication based on bacterial quorum sensing systems. The rational design process and simulation tools employed in this study provide an example for future engineering of complex synthetic gene networks comprising multiple control system motifs.

Dynamic control in a coordinated multi-cellular maze solving system

Proteins can function as biomarkers of pathological conditions, such as neurodegenerative diseases, infections or metabolic syndromes. Engineering cells to sense and respond to these biomarkers may help the understanding of molecular mechanisms underlying pathologies, as well as to develop new cell-based therapies. While several systems that detect extracellular proteins have been developed, a modular framework that can be easily re-engineered to sense different intracellular proteins was missing.
Here, we describe a protocol to implement a modular genetic platform that senses intracellular proteins and activates a specific cellular response. The device operates on intracellular antibodies or small peptides to sense with high specificity the protein of interest, triggering the transcriptional activation of output genes, through a TEV protease (TEVp)-based actuation module. TEVp is a viral protease that selectively cleaves short cognate peptides and is widely used in biotechnology and synthetic biology for its high orthogonality to the cleavage site. Specifically, we engineered devices that recognize and respond to protein-biomarkers of viral infections and genetic diseases, including mutated huntingtin, NS3 serine-protease, Tat and Nef proteins to detect Huntington’s disease, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections, respectively. Importantly, the system can be hand tailored for the desired input-output functional outcome, such as fluorescent readouts for biosensors, stimulation of antigen presentation for immune response, or initiation of apoptosis to eliminate unhealthy cells.

Ron Weiss

Papers

Synthesizing Diverse, High-Quality Audio Textures.

Engineering a heterogeneous tissue from pluripotent stem cells

Cellular expression through morphogen delivery by light activated magnetic microrobots

Dynamic control in a coordinated multi-cellular maze solving system

Engineering Intracellular Protein Sensors in Mammalian Cells