Robotics: self-reproducing machines

Self-reproduction is central to biological life for long-term sustainability and evolutionary adaptation. Although these traits would also be desirable in many engineered systems, the principles of self-reproduction have not been exploited in machine design. Here we create simple machines that act as autonomous modular robots and are capable of physical self-reproduction using a set of cubes.     

Distinct epigenetic changes in the stromal cells of breast cancers

Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. Although epigenetic modifications of the neoplastic cells in tumors have been firmly implicated in tumorigenesis, it is not known whether epigenetic modifications occur in the non-neoplastic stromal cells. To address this question in an unbiased and genome-wide manner, we developed a new method, methylation-specific digital karyotyping, and applied it to epithelial and myoepithelial cells, stromal fibroblasts from normal breast tissue, and in situ and invasive breast carcinomas. Our analyses showed that distinct epigenetic alterations occur in all three cell types during breast tumorigenesis in a tumor stage- and cell type-specific manner, suggesting that epigenetic changes have a role in the maintenance of the abnormal cellular microenvironment in breast cancer.     

Clustering and isolation in the consensus problem for partitions

We examine the problem of aggregating several partitions of a finite set into a single consensus partition We note that the dual concepts of clustering and isolation are especially significant in this connection. The hypothesis that a consensus partition should respect unanimity with respect to either concept leads us to stress a consensus interval rather than a single partition. The extremes of this interval are characterized axiomatically. If a sufficient totality of traits has been measured, and if measurement errors are independent, then a true classifying partition can be expected to lie in the consensus interval. The structure of the partitions in the interval lends itself to partial solutions of the consensus problem Conditional entropy may be used to quantify the uncertainty inherent in the interval as a whole     

Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT₁ receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT₁ antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT₁ cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.     

Structure of the insulin receptor ectodomain reveals a folded-over conformation

The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding.     

Atom-by-atom analysis of global downhill protein folding

Protein folding is an inherently complex process involving coordination of the intricate networks of weak interactions that stabilize native three-dimensional structures. In the conventional paradigm, simple protein structures are assumed to fold in an all-or-none process that is inaccessible to experiment. Existing experimental methods therefore probe folding mechanisms indirectly. A widely used approach interprets changes in protein stability and/or folding kinetics, induced by engineered mutations, in terms of the structure of the native protein. In addition to limitations in connecting energetics with structure, mutational methods have significant experimental uncertainties and are unable to map complex networks of interactions. In contrast, analytical theory predicts small barriers to folding and the possibility of downhill folding. These theoretical predictions have been confirmed experimentally in recent years, including the observation of global downhill folding. However, a key remaining question is whether downhill folding can indeed lead to the high-resolution analysis of protein folding processes. Here we show, with the use of nuclear magnetic resonance (NMR), that the downhill protein BBL from Escherichia coli unfolds atom by atom starting from a defined three-dimensional structure. Thermal unfolding data on 158 backbone and side-chain protons out of a total of 204 provide a detailed view of the structural events during folding. This view confirms the statistical nature of folding, and exposes the interplay between hydrogen bonding, hydrophobic forces, backbone conformation and side-chain entropy. From the data we also obtain a map of the interaction network in this protein, which reveals the source of folding cooperativity. Our approach can be extended to other proteins with marginal barriers (less than 3RT), providing a new tool for the study of protein folding.     

二十一世纪的矿业仍是一个崭新的技术领域

针对人类社会发展与地下矿产资源相对短缺的矛盾，阐述了新千年的采矿业必须通过一场新的技术革命，彻底改变传统的生产工艺，合理、有效地利用地下资源，保护环境。同时在分析目前采矿业科技发展现状的基础上，论述了基础理论和实用技术的研究方向。     

Collecting airs and ideas: Priestley’s style of experimental reasoning

It has often been claimed that Priestley was a skilful experimenter who lacked the capacities to analyze his own experiments and bring them to a theoretical closure. In attempts to revise this view some scholars have alluded to Priestley’s ‘synoptic’ powers while others stressed the contextual role of British Enlightenment in understanding his chemical research. A careful analysis of his pneumatic reports, privileging the dynamics of his experimental practice, uncovers significant yet neglected aspects of Priestley’s science. By focusing on his early experimental conduct and writing on nitrous air, I demonstrate how his methodological and rhetorical devices, far from being consequences of compulsive writing or theoretical naïveté, were deeply entwined with his chemical research. I employ the notion of ‘style of experimental reasoning’ (SER)—derived from A. C. Crombie and I. Hacking—to shed light on the intersection at which Priestley’s unique method, literary style, and epistemology converged to generate scientific knowledge. Establishing Priestley’s SER advances a finer understanding of the interactive character of his pneumatic experimentalism, peculiar dimensions of which have evaded both traditional as well as revisionist scholarship, thus infusing the longstanding historiographic debate over his scientific merits.     

微波结构分析的奇异积分方程方法

上世纪70年代以来与微波结构有关的某些计算问题通常是借助共形映射解析解决，且限于一维或二维情形（近年来由于计算机的发展被扩充到三维的某些情形）。本书作者积30多年的经验创立了一种新的方法——基于奇异积分方程（SIE）理论，给出边值问题解的积分表示，从而确定某些二维和三维微波结构的电动力学特性。本书系统全面地论述了这种方法，包括理论基础、用于数值分析的一些算法、以及各种典型应用实例。