Initial genome sequencing and analysis of multiple myeloma

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.     

Downregulation of enkephalin-mediated inflammatory responses by CD10/neutral endopeptidase 24.11.

The antigen CD10 (common acute lymphoblastic leukaemia antigen), which is the zinc metalloprotease, neutral endopeptidase 24.11 (also known as NEP or 'enkephalinase'), is expressed by acute lymphoblastic leukaemias, normal lymphoid progenitors, mature polymorphonuclear leukocytes and certain nonhaematopoietic cells. CD10/NEP hydrolyses several naturally occurring peptides, including the endogenous opioid pentapeptides Met- and Leu-enkephalin. In invertebrate organisms such as the mollusc Mytilus edulis, Met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration and aggregation of haemocytes. We report here that a structure related to CD10/NEP is expressed by M. edulis haemocytes and that abrogation of CD10/NEP enzymatic activity reduces the amount of Met-enkephalin required for haemocyte activation by five orders of magnitude. Similar results are obtained with CD10+ human polymorphonuclear leukocytes, indicating that CD10/NEP related structures regulate enkephalin-mediated inflammatory responses in organisms whose ancestors diverged approximately 500 million years ago.     

Femtosecond time-delay X-ray holography

Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging can be used to achieve high resolution, beyond radiation damage limits for biological samples. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.     

行星着陆——推进下降过程的建模与控制(英文)

登陆火星或月球时,释放降落伞后进入推进阶段,通过轴向推力倾斜实现水平方向运动,能够与速度矢量(重力)的相反方向一致或与需要的加速度方向保持一致.后一种策略能实现精确着陆,在该策略下,倾斜角(俯仰角和偏转角)与水平加速度成正比.这种策略并未采用以水平加速度为姿态控制目标的递阶导航与控制方案,而是基于角加速度对位置作用的四阶动力学特性设计了一个独特的控制系统.除去倾斜角的非线性因素(垂直制动规定的轴向推力)后,系统综合动力学方程能够实现(准)输入-状态线性化.论文同时表明:一方面,基于参考轨迹(倾斜角和位置)的控制器设计仅能实现部分输入-状态线性化;另一方面,系统的内部稳定性可以证明.即使存在不可镇定的外部干扰动力学模态时,仍能确保系统稳定性.蒙特卡洛仿真验证了闭环控制策略的有效性.     

Feyerabend,truth, and relativisms: Footnotes to the Italian debate

There is a substantial literature on Feyerabend's relativism—including a few papers in this collection—but fewer specific studies of the ways that his writings and ideas have been taken up among the non-academic public. This is odd, given his obvious interest in the lives and concerns of persons who were not ‘intellectuals’—a term that, for him, had a pejorative ring to it. It is also odd, given the abundance of evidence of how Feyerabend's relativism played a role in a specific national and cultural context—namely, contemporary Italian debates about relativism. This paper offers a study of how Feyerabend's ideas have been deployed by Italian intellectuals and cultural commentators—including the current Pope—and critically assesses them.     

Scalarolbutenolide,a new sesterterpenoid from the marine spongeSpongia nitens

Summary A new sesterterpenoid, scalarolbutenolide (5), has been isolated from the marine spongeSpongia nitens; its structure, including the absolute stereochemistry, has been established by chemical and spectroscopic studies.This work is a part of the Progetto Finalizzato per l'Oceanografia e i Fondi Marini, C.N.R., Roma.We are indebted to A. Crispino, C. Di Pinto, G. Scognamiglio and R. Turco for their technical assistance.