Loss-of-function mutations in sodium channel Nav1.7 cause anosmia

Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.     

Heat driven refrigeration cycle at low temperatures

Absorption refrigeration cycle can be driven by low-grade thermal energy, such as solar energy, geothermal energy and waste heat. It is beneficial to save energy and protect environment. However, the applications of traditional absorption refrigeration cycle are greatly restricted because they cannot achieve low refrigeration temperature. A new absorption refrigeration cycle is investigated in this paper, which is driven by low-grade energy and can get deep low refrigeration temperature. The mixture refrigerant R23 R134a and an absorbent DMF are used as its working fluid. The theoretical results indicate that the new cyde can achieve -62℃ refrigeration temperature when the generation temperature is only 160℃. This refrigeration temperature is much lower than that obtained by traditional absorption refrigeration cycle. Refrigeration temperature of -47.3℃ has been successfully achieved by experiment for this new cycle at the generation temperature of 157~C, which is the lowest temperature obtained by absorption refrigeration system reported in the literature up to now. The theoretical and experimental results prove that new cycle can achieve rather low refrigeration temperature.     

The mammalian sodium channel BNC1 is required for normal touch sensation

Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that it might be a part of such a mechanosensor. Here we show that disrupting the mouse BNC1 gene markedly reduces the sensitivity of a specific component of mechanosensation: low-threshold rapidly adapting mechanoreceptors. In rodent hairy skin these mechanoreceptors are excited by hair movement. Consistent with this function, we found BNC1 in the lanceolate nerve endings that lie adjacent to and surround the hair follicle. Although BNC1 has been proposed to have a role in pH sensing, the acid-evoked current in cultured sensory neurons and the response of acid-stimulated nociceptors were normal in BNC1 null mice. These data identify the BNC1 channel as essential for the normal detection of light touch and indicate that BNC1 may be a central component of a mechanosensory complex.     

The large-conductance Ca2+-activated K+ channel is essential for innate immunity

Neutrophil leukocytes have a pivotal function in innate immunity. Dogma dictates that the lethal blow is delivered to microbes by reactive oxygen species (ROS) and halogens, products of the NADPH oxidase, whose impairment causes immunodeficiency. However, recent evidence indicates that the microbes might be killed by proteases, activated by the oxidase through the generation of a hypertonic, K+-rich and alkaline environment in the phagocytic vacuole. Here we show that K+ crosses the membrane through large-conductance Ca2+-activated K+ (BK(Ca)) channels. Specific inhibitors of these channels, iberiotoxin and paxilline, blocked oxidase-induced 86Rb+ fluxes and alkalinization of the phagocytic vacuole, whereas NS1619, a BK(Ca) channel opener, enhanced both. Characteristic outwardly rectifying K+ currents, reversibly inhibited by iberiotoxin, were demonstrated in neutrophils and eosinophils and the expression of the alpha-subunit of the BK channel was confirmed by western blotting. The channels were opened by the combination of membrane depolarization and elevated Ca2+ concentration, both consequences of oxidase activity. Remarkably, microbial killing and digestion were abolished when the BK(Ca) channel was blocked, revealing an essential and unexpected function for this K+ channel in the microbicidal process.     

Orai1 is an essential pore subunit of the CRAC channel

Stimulation of immune cells causes depletion of Ca2+ from endoplasmic reticulum (ER) stores, thereby triggering sustained Ca2+ entry through store-operated Ca2+ release-activated Ca2+ (CRAC) channels, an essential signal for lymphocyte activation and proliferation. Recent evidence indicates that activation of CRAC current is initiated by STIM proteins, which sense ER Ca2+ levels through an EF-hand located in the ER lumen and relocalize upon store depletion into puncta closely associated with the plasma membrane. We and others recently identified Drosophila Orai and human Orai1 (also called TMEM142A) as critical components of store-operated Ca2+ entry downstream of STIM. Combined overexpression of Orai and Stim in Drosophila cells, or Orai1 and STIM1 in mammalian cells, leads to a marked increase in CRAC current. However, these experiments did not establish whether Orai is an essential intracellular link between STIM and the CRAC channel, an accessory protein in the plasma membrane, or an actual pore subunit. Here we show that Orai1 is a plasma membrane protein, and that CRAC channel function is sensitive to mutation of two conserved acidic residues in the transmembrane segments. E106D and E190Q substitutions in transmembrane helices 1 and 3, respectively, diminish Ca2+ influx, increase current carried by monovalent cations, and render the channel permeable to Cs+. These changes in ion selectivity provide strong evidence that Orai1 is a pore subunit of the CRAC channel.     

低温下钢材应变强化系数的测定

设计了在低温下不用引伸计测定钢材应变强化系数ｎ值的方法，在系列温度下测定了１６ＭｎＲ，４０ＣｒＮｉＭｏ和ＷＣＦ６２三种钢材的ｎ值，发现材料的ｎ值随试验温度的降低而下降，其部分原因是由于屈服强度的升高使材料的应变强化能力相对下降．实验结果还表明按幂强化关系来描述材料应变强化规律的Ｈｏｌｌｏｍｏｎ关系和Ｒａｍｂｅｒｇ－Ｏｓｇｏｏｄ关系，在工程意义上可认为是相同的．     

低信噪比多径-信道下的OFDM带宽自动估计

针对低信噪比多径-信道条件下正交频分复用(OFDM)信号带宽估计精度低的问题,提出一种基于小波变换的OFDM信号带宽自动估计方法。首先利用修正周期图法(Welch法)得到信号瞬时功率谱,通过多次观察测量并对功率谱曲线进行统计平均。然后对功率谱曲线进行连续小波变换,计算小波变换后时间-尺度平面上同一时间不同尺度能量累计曲线,提取曲线局部峰值位置,进而估计信号带宽。实验仿真结果表明：在不同多径信道且信噪比为-10dB条件下,估计偏差均不超过1.2%,准确度优于传统方法,且鲁棒性较强。     

The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities

Voltage-sensitive membrane channels, the sodium channel, the potassium channel and the calcium channel operate together to amplify, transmit and generate electric pulses in higher forms of life. Sodium and calcium channels are involved in cell excitation, neuronal transmission, muscle contraction and many functions that relate directly to human diseases. Sodium channels--glycosylated proteins with a relative molecular mass of about 300,000 (ref. 5)--are responsible for signal transduction and amplification, and are chief targets of anaesthetic drugs and neurotoxins. Here we present the three-dimensional structure of the voltage-sensitive sodium channel from the eel Electrophorus electricus. The 19 A structure was determined by helium-cooled cryo-electron microscopy and single-particle image analysis of the solubilized sodium channel. The channel has a bell-shaped outer surface of 135 A in height and 100 A in side length at the square-shaped bottom, and a spherical top with a diameter of 65 A. Several inner cavities are connected to four small holes and eight orifices close to the extracellular and cytoplasmic membrane surfaces. Homologous voltage-sensitive calcium and tetrameric potassium channels, which regulate secretory processes and the membrane potential, may possess a related structure.     

Direct observation of Tomonaga-Luttinger-liquid state in carbon nanotubes at low temperatures

The electronic transport properties of conventional three-dimensional metals are successfully described by Fermi-liquid theory. But when the dimensionality of such a system is reduced to one, the Fermi-liquid state becomes unstable to Coulomb interactions, and the conduction electrons should instead behave according to Tomonaga-Luttinger-liquid (TLL) theory. Such a state reveals itself through interaction-dependent anomalous exponents in the correlation functions, density of states and momentum distribution of the electrons. Metallic single-walled carbon nanotubes (SWNTs) are considered to be ideal one-dimensional systems for realizing TLL states. Indeed, the results of transport measurements on metal-SWNT and SWNT-SWNT junctions have been attributed to the effects of tunnelling into or between TLLs, although there remains some ambiguity in these interpretations. Direct observations of the electronic states in SWNTs are therefore needed to resolve these uncertainties. Here we report angle-integrated photoemission measurements of SWNTs. Our results reveal an oscillation in the pi-electron density of states owing to one-dimensional van Hove singularities, confirming the one-dimensional nature of the valence band. The spectral function and intensities at the Fermi level both exhibit power-law behaviour (with almost identical exponents) in good agreement with theoretical predictions for the TLL state in SWNTs.     

SO_2对低温NO催化氧化活性的增强效应

研究了SO2 对NO催化氧化过程的影响 ,考察了SO2 存在前后γ Al2 O3 及其负载NiO催化剂对NO的氧化活性 ,发现在较低温度 (15 0℃ )反应时 ,在较长一段时间内SO2 对NO氧化有促进作用 .同时运用BET ,XRD ,固体酸测定及TPD等方法 ,比较了SO2 处理前后载体及催化剂的结构和性能 ,并对SO2 的增强效应提出了看法     

相对论q形变理想费米气体的低温热力学统计性质

在q形变费米-狄拉克分布函数的基础上，研究了相对论q形变理想费米气体的低温热力学统计性质，得到了一些重要热力学量例如费米能，基态能，化学势，总能和热容量的解析表达式，揭示了q形变参数和相对论对系统性质的影响。结果表明：q形变导致了一些与正常的系统不同的新奇特性，另外，相对论费米系统的性质与非相对论系统的性质明显不同。     

钢轨钢材低温冲击功的试验研究

钢轨钢材低温下抵抗冲击的韧性变差,极易发生脆性断裂,因此很有必要研究其低温下的冲击功。该文在 20℃至-60℃范围内测量了中国常用钢轨钢材U71Mn和U75V的U型缺口和V型缺口冲击功。试验结果显示,这2种钢轨钢材的冲击功随温度的降低而明显降低。该文利用Boltzmann函数对试验结果进行了回归分析,得到了回归方程式,指出钢轨钢材U71Mn和U75V的韧脆转变温度分别在-10℃和 5℃附近,且由回归方程可以预测2种钢轨钢材 20℃至-60℃温度区间内的冲击功。试验结果表明,在青藏铁路等寒冷地区的铁路工程中宜优先选用U71Mn钢材。     

钢轨钢材低温冲击功的试验研究

钢轨钢材低温下抵抗冲击的韧性变差,很易发生脆性断裂,因此很有必要研究其低温下的冲击功。该文在 20℃至-60℃范围内测量了中国常用钢轨钢材U71Mn和U75V的U型缺口和V型缺口冲击功。试验结果显示,两种钢轨钢材的冲击功随温度的降低而明显降低。该文利用Boltzmann函数对试验结果进行了回归分析,得到了回归方程式,指出钢轨钢材U71Mn和U75V的韧脆转变温度分别在-10℃和 5℃附近,且由回归方程可以预测两种钢轨钢材 20℃至-60℃温度区间内的冲击功。试验结果表明,在青藏铁路等寒冷地区的铁路工程中宜优先选用U71Mn钢材。     

相对论q形变理想费米气体的低温热力学统计性质

在q形变费米-狄拉克分布函数的基础上,研究了相对论q形变理想费米气体的低温热力学统计性质,得到了一些重要热力学量例如费米能,基态能,化学势,总能和热容量的解析表达式,揭示了q形变参数和相对论对系统性质的影响.结果表明:q形变导致了一些与正常的系统不同的新奇特性,另外,相对论费米系统的性质与非相对论系统的性质明显不同.     

高低温下复合绝缘子抗拉性能试验

复合绝缘子是由芯体和装配有金属附件的外套构成。芯体多采用环氧树脂浸渍的玻璃纤维增强塑料制成,是一种强度高、非脆性复合材料。但在芯棒与伞套之间的粘结层是薄弱环节,在大温差地区容易受力学破坏。文中采用Instron1186电子万能试验机,通过位移控制进行材料力学性能试验,研究复合绝缘子分别在高低温作用下的抗拉性能。试验表明,复合绝缘子机械破坏负荷取决于金具与芯棒连接强度,其破坏的主要特征为端部金具的滑移。因为端部金具的热膨胀系数与玻璃纤维增强环氧树脂芯棒有较大差异,无论是在高温还是低温,复合绝缘子的力学性能均较常温状态产生下滑,尤其是高温下,金具与芯棒的黏结-滑移性能会降低50%甚至更多。     

Lysyl oxidase is essential for hypoxia-induced metastasis

Metastasis is a multistep process responsible for most cancer deaths, and it can be influenced by both the immediate microenvironment (cell-cell or cell-matrix interactions) and the extended tumour microenvironment (for example vascularization). Hypoxia (low oxygen) is clinically associated with metastasis and poor patient outcome, although the underlying processes remain unclear. Microarray studies have shown the expression of lysyl oxidase (LOX) to be elevated in hypoxic human tumour cells. Paradoxically, LOX expression is associated with both tumour suppression and tumour progression, and its role in tumorigenesis seems dependent on cellular location, cell type and transformation status. Here we show that LOX expression is regulated by hypoxia-inducible factor (HIF) and is associated with hypoxia in human breast and head and neck tumours. Patients with high LOX-expressing tumours have poor distant metastasis-free and overall survivals. Inhibition of LOX eliminates metastasis in mice with orthotopically grown breast cancer tumours. Mechanistically, secreted LOX is responsible for the invasive properties of hypoxic human cancer cells through focal adhesion kinase activity and cell to matrix adhesion. Furthermore, LOX may be required to create a niche permissive for metastatic growth. Our findings indicate that LOX is essential for hypoxia-induced metastasis and is a good therapeutic target for preventing and treating metastases.