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

The Spliceosome: Design Principles of a Dynamic RNP Machine

We review the field of femtosecond pulse shaping, in which Fourier synthesis methods are used to generate nearly arbitrarily shaped ultrafast optical wave forms according to user specification. An emphasis is placed on programmable pulse shaping methods based on the use of spatial light modulators. After outlining the fundamental principles of pulse shaping, we then present a detailed discussion of pulse shaping using several different types of spatial light modulators. Finally, new research directions in pulse shaping, and applications of pulse shaping to optical communications, biomedical optical imaging, high power laser amplifiers, quantum control, and laser-electron beam interactions are reviewed.

Femtosecond pulse shaping using spatial light modulators

Pre-mRNA splicing is catalyzed by the spliceosome, a multimegadalton ribonucleoprotein (RNP) complex comprised of five snRNPs and numerous proteins. Intricate RNA-RNA and RNP networks, which serve to align the reactive groups of the pre-mRNA for catalysis, are formed and repeatedly rearranged during spliceosome assembly and catalysis. Both the conformation and composition of the spliceosome are highly dynamic, affording the splicing machinery its accuracy and flexibility, and these remarkable dynamics are largely conserved between yeast and metazoans. Because of its dynamic and complex nature, obtaining structural information about the spliceosome represents a major challenge. Electron microscopy has revealed the general morphology of several spliceosomal complexes and their snRNP subunits, and also the spatial arrangement of some of their components. X-ray and NMR studies have provided high resolution structure information about spliceosomal proteins alone or complexed with one or more binding partners. The extensive interplay of RNA and proteins in aligning the pre-mRNA's reactive groups, and the presence of both RNA and protein at the core of the splicing machinery, suggest that the spliceosome is an RNP enzyme. However, elucidation of the precise nature of the spliceosome's active site, awaits the generation of a high-resolution structure of its RNP core.

/pdf/spliceosome-structure-and-function-3j278at609.pdf

Spliceosome structure and function.

A large-scale silicon nanophotonic phased array with more than 4,000 antennas is demonstrated using a state-of-the-art complementary metal-oxide–semiconductor (CMOS) process, enabling arbitrary holograms with tunability, which brings phased arrays to many new technological territories. Nanophotonic approaches allow the construction of chip-scale arrays of optical nanoantennas capable of producing radiation patterns in the far field. This could be useful for a range of applications in communications, LADAR (laser detection and ranging) and three-dimensional holography. Until now this technology has been restricted to one-dimensional or small two-dimensional arrays. This paper reports the construction of a large-scale silicon nanophotonic phased array containing 4,096 optical nanoantennas balanced in power and aligned in phase. The array was used to generate a complex radiation pattern—the MIT logo—in the far field. The authors show that this type of nanophotonic phased array can be actively tuned, and in some cases the beam is steerable. Electromagnetic phased arrays at radio frequencies are well known and have enabled applications ranging from communications to radar, broadcasting and astronomy1. The ability to generate arbitrary radiation patterns with large-scale phased arrays has long been pursued. Although it is extremely expensive and cumbersome to deploy large-scale radiofrequency phased arrays2, optical phased arrays have a unique advantage in that the much shorter optical wavelength holds promise for large-scale integration3. However, the short optical wavelength also imposes stringent requirements on fabrication. As a consequence, although optical phased arrays have been studied with various platforms4,5,6,7,8 and recently with chip-scale nanophotonics9,10,11,12, all of the demonstrations so far are restricted to one-dimensional or small-scale two-dimensional arrays. Here we report the demonstration of a large-scale two-dimensional nanophotonic phased array (NPA), in which 64 × 64 (4,096) optical nanoantennas are densely integrated on a silicon chip within a footprint of 576 μm × 576 μm with all of the nanoantennas precisely balanced in power and aligned in phase to generate a designed, sophisticated radiation pattern in the far field. We also show that active phase tunability can be realized in the proposed NPA by demonstrating dynamic beam steering and shaping with an 8 × 8 array. This work demonstrates that a robust design, together with state-of-the-art complementary metal-oxide–semiconductor technology, allows large-scale NPAs to be implemented on compact and inexpensive nanophotonic chips. In turn, this enables arbitrary radiation pattern generation using NPAs and therefore extends the functionalities of phased arrays beyond conventional beam focusing and steering, opening up possibilities for large-scale deployment in applications such as communication, laser detection and ranging, three-dimensional holography and biomedical sciences, to name just a few.

/pdf/large-scale-nanophotonic-phased-array-c260q1wn41.pdf

Large-scale nanophotonic phased array

Optical phased arrays represent an enabling new technology that makes possible simple affordable, lightweight, optical sensors offering very precise stabilization, random-access pointing programmable multiple simultaneous beams, a dynamic focus/defocus capability, and moderate to excellent optical power handling capability. These new arrays steer or otherwise operate on an already formed beam. A phase profile is imposed on an optical beam as it is either transmitted through or reflected from the phase shifter array. The imposed phase profile steers, focuses, fans out, or corrects phase aberrations on the beam. The array of optical phase shifters is realized through lithographic patterning of an electrical addressing network on the superstrate of a liquid crystal waveplate. Refractive index changes sufficiently large to realize full-wave differential phase shifts can be effected using low (<10 V) voltages applied to the liquid crystal phase plate electrodes. High efficiency large-angle steering with phased arrays requires phase shifter spacing on the order of a wavelength or less; consequently addressing issues make 1-D optical arrays much more practical than 2-D arrays. Orthogonal oriented 1-D phased arrays are used to deflect a beam in both dimensions. Optical phased arrays with apertures on the order of 4 cm by 4 cm have been fabricated for steering green, red, 1.06 /spl mu/m, and 10.6 /spl mu/m radiation. System concepts that include a passive acquisition sensor as well as a laser radar are presented.

Optical phased array technology

Efficient, electrically tunable, agile, inertialess, near-diffraction-limited one-dimensional optical beam steering is demonstrated at the infrared wavelength of 10.6 microm with a liquid-crystal phased array.

High-efficiency liquid-crystal optical phased-array beam steering

The spliceosome is the complex macromolecular machine responsible for removing introns from precursors to messenger RNAs (pre-mRNAs). We combined yeast genetic engineering, chemical biology, and multiwavelength fluorescence microscopy to follow assembly of single spliceosomes in real time in whole-cell extracts. We find that individual spliceosomal subcomplexes associate with pre-mRNA sequentially via an ordered pathway to yield functional spliceosomes and that association of every subcomplex is reversible. Further, early subcomplex binding events do not fully commit a pre-mRNA to splicing; rather, commitment increases as assembly proceeds. These findings have important implications for the regulation of alternative splicing. This experimental strategy should prove widely useful for mechanistic analysis of other macromolecular machines in environments approaching the complexity of living cells.

/pdf/ordered-and-dynamic-assembly-of-single-spliceosomes-1bh46iyrp1.pdf

Ordered and Dynamic Assembly of Single Spliceosomes

https://www.cell.com/cell/pdf/S0092-8674(15)00265-2.pdf

Larry J. Friedman

Papers

Optical phased array technology

High-efficiency liquid-crystal optical phased-array beam steering

Ordered and Dynamic Assembly of Single Spliceosomes

Single-Molecule Studies of Origin Licensing Reveal Mechanisms Ensuring Bidirectional Helicase Loading

Viewing dynamic assembly of molecular complexes by multi-wavelength single-molecule fluorescence.