Development of new hypoxic cell sensitizers: Amides of nitrobenzoic acid with spermidine and spermine

Summary New type hypoxic cell sensitizers, N¹, N¹⁰-bis(4-nitrobenzoyl)spermidine (1) and N¹,N¹⁴-bis(4-nitrobenzoyl)-spermine (2), have been developed. These compounds were shown to be more effective radiosensitizers to hypoxic cells than misonidazole (3).     

Radioprotection of LPS-resistant C3H/HeJ mice by RES-blockade

Summary The radioprotective effect of RES-blockade was studied in LPS-resistant mice. Injection of carbon particles protected these mice from radiation lethality whereas LPS did not; thus a difference in the mechanism of radioprotection was demonstrated.This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.     

Effects of three synthetic peptides analogous to neurohypophyseal hormones on the excitability of giant neurones ofAchatina fulica Férussac

Summary Deamino-dicarba-(d-d-)oxytocin andd-d-Arg-vasotocin at 10^–4 kg/l showed an excitatory effect on the periodically oxcillating neurone (PON) ofAchatina fulica Férussac.d-d-Arg-vasopressin had no effect.     

Conformational transition of Sec machinery inferred from bacterial SecYE structures

Over 30% of proteins are secreted across or integrated into membranes. Their newly synthesized forms contain either cleavable signal sequences or non-cleavable membrane anchor sequences, which direct them to the evolutionarily conserved Sec translocon (SecYEG in prokaryotes and Sec61, comprising alpha-, gamma- and beta-subunits, in eukaryotes). The translocon then functions as a protein-conducting channel. These processes of protein localization occur either at or after translation. In bacteria, the SecA ATPase drives post-translational translocation. The only high-resolution structure of a translocon available so far is that for SecYEbeta from the archaeon Methanococcus jannaschii, which lacks SecA. Here we present the 3.2-A-resolution crystal structure of the SecYE translocon from a SecA-containing organism, Thermus thermophilus. The structure, solved as a complex with an anti-SecY Fab fragment, revealed a 'pre-open' state of SecYE, in which several transmembrane helices are shifted, as compared to the previous SecYEbeta structure, to create a hydrophobic crack open to the cytoplasm. Fab and SecA bind to a common site at the tip of the cytoplasmic domain of SecY. Molecular dynamics and disulphide mapping analyses suggest that the pre-open state might represent a SecYE conformational transition that is inducible by SecA binding. Moreover, we identified a SecA-SecYE interface that comprises SecA residues originally buried inside the protein, indicating that both the channel and the motor components of the Sec machinery undergo cooperative conformational changes on formation of the functional complex.     

How kinesin waits between steps

Kinesin-1 (conventional kinesin) is a dimeric motor protein that carries cellular cargoes along microtubules by hydrolysing ATP and moving processively in 8-nm steps. The mechanism of processive motility involves the hand-over-hand motion of the two motor domains ('heads'), a process driven by a conformational change in the neck-linker domain of kinesin. However, the 'waiting conformation' of kinesin between steps remains controversial-some models propose that kinesin adopts a one-head-bound intermediate, whereas others suggest that both the kinesin heads are bound to adjacent tubulin subunits. Addressing this question has proved challenging, in part because of a lack of tools to measure structural states of the kinesin dimer as it moves along a microtubule. Here we develop two different single-molecule fluorescence resonance energy transfer (smFRET) sensors to detect whether kinesin is bound to its microtubule track by one or two heads. Our FRET results indicate that, while moving in the presence of saturating ATP, kinesin spends most of its time bound to the microtubule with both heads. However, when nucleotide binding becomes rate-limiting at low ATP concentrations, kinesin waits for ATP in a one-head-bound state and makes brief transitions to a two-head-bound intermediate as it walks along the microtubule. On the basis of these results, we suggest a model for how transitions in the ATPase cycle position the two kinesin heads and drive their hand-over-hand motion.     

Energy doubling of 42 GeV electrons in a metre-scale plasma wakefield accelerator

The energy frontier of particle physics is several trillion electron volts, but colliders capable of reaching this regime (such as the Large Hadron Collider and the International Linear Collider) are costly and time-consuming to build; it is therefore important to explore new methods of accelerating particles to high energies. Plasma-based accelerators are particularly attractive because they are capable of producing accelerating fields that are orders of magnitude larger than those used in conventional colliders. In these accelerators, a drive beam (either laser or particle) produces a plasma wave (wakefield) that accelerates charged particles. The ultimate utility of plasma accelerators will depend on sustaining ultrahigh accelerating fields over a substantial length to achieve a significant energy gain. Here we show that an energy gain of more than 42 GeV is achieved in a plasma wakefield accelerator of 85 cm length, driven by a 42 GeV electron beam at the Stanford Linear Accelerator Center (SLAC). The results are in excellent agreement with the predictions of three-dimensional particle-in-cell simulations. Most of the beam electrons lose energy to the plasma wave, but some electrons in the back of the same beam pulse are accelerated with a field of approximately 52 GV m(-1). This effectively doubles their energy, producing the energy gain of the 3-km-long SLAC accelerator in less than a metre for a small fraction of the electrons in the injected bunch. This is an important step towards demonstrating the viability of plasma accelerators for high-energy physics applications.     

The molecular organization of cypovirus polyhedra

Cypoviruses and baculoviruses are notoriously difficult to eradicate because the virus particles are embedded in micrometre-sized protein crystals called polyhedra. The remarkable stability of polyhedra means that, like bacterial spores, these insect viruses remain infectious for years in soil. The environmental persistence of polyhedra is the cause of significant losses in silkworm cocoon harvests but has also been exploited against pests in biological alternatives to chemical insecticides. Although polyhedra have been extensively characterized since the early 1900s, their atomic organization remains elusive. Here we describe the 2 A crystal structure of both recombinant and infectious silkworm cypovirus polyhedra determined using crystals 5-12 micrometres in diameter purified from insect cells. These are the smallest crystals yet used for de novo X-ray protein structure determination. We found that polyhedra are made of trimers of the viral polyhedrin protein and contain nucleotides. Although the shape of these building blocks is reminiscent of some capsid trimers, polyhedrin has a new fold and has evolved to assemble in vivo into three-dimensional cubic crystals rather than icosahedral shells. The polyhedrin trimers are extensively cross-linked in polyhedra by non-covalent interactions and pack with an exquisite molecular complementarity similar to that of antigen-antibody complexes. The resulting ultrastable and sealed crystals shield the virus particles from environmental damage. The structure suggests that polyhedra can serve as the basis for the development of robust and versatile nanoparticles for biotechnological applications such as microarrays and biopesticides.     

基于数据的建筑能耗分析与建模

对建筑能耗数据进行深入分析,提出了建立建筑电力能耗模型的方法.首先对建筑能耗进行了分项计量,统计了建筑逐时照明能耗数据,办公设备能耗数据以及办公人数,同时调查了建筑管理控制方式.经过分析可知,办公设备能耗数据与办公人数线性相关,而照明能耗数据与办公人数以及太阳辐射强度相关,但为非线性关系.根据不同类型数据的特点,分别建立了线性回归模型以及决策树模型.该模型可以预测建筑能耗并评估建筑管理方式对能耗的影响.     

Primary structure and functional expression from complementary DNA of a brain calcium channel.

The primary structure of a voltage-dependent calcium channel from rabbit brain has been deduced by cloning and sequencing the complementary DNA. Calcium channel activity expressed from the cDNA is dramatically increased by coexpression of the alpha 2 and beta subunits, known to be associated with the dihydropyridine receptor. This channel is a high voltage-activated calcium channel that is insensitive both to nifedipine and to omega-conotoxin. We suggest that it is expressed predominantly in cerebellar Purkinje cells and granule cells.