A comparison of power losses for small (< 1 kW) induction motor drives adopting squarewave and sinusoidal PWM excitation

In this paper the influence of the form of motor excitation on the performance of a small (< 1 kW) induction motor drive is studied. Two forms of excitation, namely sine waves generated by pulse width modulation and simple square wave are explored. Sine wave excitation gives lower motor losses but increases inverter losses. Conversely, square wave excitation increases motor losses but decreases inverter losses. Losses have been measured directly by calorimetric means or, in the case of the inverter, predicted by a Pspice model that has been verified by calorimetric methods. The work shows that overall, the use of square wave excitation leads to a more efficient drive. © 2004 The Institution of Electrical Engineers.

Changes of tissue endothelin-1 and nitric oxide synthase in a sheep model of large intestinal obstruction

Large intestinal obstruction (LIO) in farm animals can cause a ischaemic necrosis of intestinal tissue, eventually leading to death. The roles of endothelin-1 (ET-1) and nitric oxide (NO) are not well understood in the process of LIO, but evidence suggests that endothelial-derived mediators may participate. In the present study, ET-1 concentration and total nitric oxide synthase (NOS) activity were measured in heart, liver, pancreas, lung and kidney in a model of LIO in sheep. Our data demonstrated that ET-1 concentration and NOS activity were altered, with significant increases of ET-1 in heart, lung and kidney and of NOS activity in pancreas and kidney, but a marked decline of NOS activity in liver (p<0.05). It is postulated that these alterations in NOS activity and ET-1 concentration may contribute to the progressive loss of organ function, and finally lead to death in LIO in sheep.

Morphine induces Beclin 1-and ATG5-dependent autophagy in human neuroblastoma SH-SY5Y cells and in the rat hippocampus

Chronic exposure to morphine can induce drug addiction and neural injury, but the exact mechanism is not fully understood. Here we show that morphine induces autophagy in neuroblastoma SH-SY5Y cells and in the rat hippocampus. Pharmacological approach shows that this effect appears to be mediated by PTX-sensitive G protein-coupled receptors signaling cascade. Morphine increases Beclin 1 expression and reduces the interaction between Beclin 1 and Bcl-2, thus releasing Beclin 1 for its pro-autophagic activity. Bcl-2 overexpression inhibits morphine-induced autophagy, whereas knockdown of Beclin 1 or knockout of ATG5 prevents morphine-induced autophagy. In addition, chronic treatment with morphine induces cell death, which is increased by autophagy inhibition through Beclin 1 RNAi. Our data are the first to reveal that Beclin 1 and ATG5 play key roles in morphine-induced autophagy, which may contribute to morphine-induced neuronal injury.

Angular dependent characteristics of a 1.3-mu m GaInNAs/GaAs quantum-well resonant cavity enhanced photodetect

Characteristics of a 1.3-mum GaInNAs RCE PD with respect to the incident light angle were analyzed both in theoretical simulation and experiments. The results show the influence can be neglected when the light incidence angle is less than 3degrees. This is a requirement for the PD to be applied in WDM networks. (C) 2002 Wiley Periodicals, Inc.

GaInNAs/GaAs multiple-quantum well resonant-cavity-enhanced photodetectors at 1.3 mu m

A GaInNAs/GaAs multiple quantum well (MQW) resonant-cavity enhanced photodetector (RCF-PD) operated at a wavelength of 1.3 mum with the full width at half maximum of 4nm has been demonstrated. The GaInNAs RCE - PD was grown by molecular beam epitaxy using a homemade ion-removed dc plasma cell as a nitrogen source. GaInNAs/GaAs MQW shows a strong exciton peak at room temperature, which is very beneficial for applications in long-wavelength absorption devices. For a 100 mum diameter RCE-PD, the dark current is 20 and 32 pA at biases of 0 and 6 V, respectively, and the breakdown voltage is - 18 V. The measured 3 dB bandwidth is 308 MHz, which is limited by the resistance of p-type distributed Bragg reflector mirror. The tunable wavelength in a range of 18 nm with the angle of incident light was observed.

Performance of palladium-containing supported catalysts in the oxidation of 1-butene

Performance of palladium-containing supported catalysts in the oxidation of 1-butene was investigated in a fixed-bed flow microreactor. The Pd-Fe-HCl/Ti-Al catalyst is the best among the five Pd-Fe-HCl/X (A = SiO2, gamma-Al2O3, Al-Ti, TiO2, MCM-22) catalysts for the oxidation of I-butene to butanone. It is interesting that high propionic acid selectivity can be obtained when V and H2SO4 are added to the palladium-containing supported catalysts.

Study of the alkylation of isobutane with n-butene over WO3/ZrO2 strong solid acid. 1. Effect of the preparation method, WO3 loading, and calcination temperature

A series of strong solid acids composed of WO3/ZrO2 were prepared. Their crystal structure, surface state, and acidity were determined by the methods of X-ray diffraction, thermal gravimetric and differential thermal analysis, temperature-programmed reduction, laser Raman, and acidity measurement. The results revealed that ZrO2 in WO3/ZrO2 existed mainly in the tetragonal phase, the addition of WO3 plays an important role in stabilizing the tetragonal phase of ZrO2, and all of the samples possessed large surface areas. WO3 in WO3/ZrO2 is mainly monolayer dispersed, and a small amount crystallized on the ZrO2 surface and partly reacted with ZrO2 to form the bond of Zr-O-W, acting as the strong solid acid center. The catalytic properties of WO3/ZrO2 strong solid;acids for alkylation of isobutane with butene at different conditions were investigated. They had a better reaction performance than other strong solid acids; a parallel relationship could be drawn between the catalytic activity and the acid amounts as well as the acidic strength of the catalysts.

温和条件下分子氧的活化和转移——Ⅰ.在三苯基膦和1-辛烯氧化中过氧酞菁钛的氧转移性能的研究

本文研究了过氧酞菁钛(PcTi0_2)在三苯基膦(Ph_3P)以及1-辛烯氧化反应中氧原子转移性能.在温和条件下,PcTiO_2可化学计量地转移一个氧原子至Ph_3P形成Ph_3O.然而,在1-辛烯的氧化反应中,只有在共催化剂,(PhCN)_2PdCl_2存在下,PcTiO_2才能将氧原子转移至被Pd化合物活化的烯烃上形成辛酮.实验结果表明,PcTiO_2在上述两个氧化反应中,只能起转移一个氧原子的作用,不可能形成以分子氧为氧化剂的催化氧化体系.

藏药1号与7号水提液对大鼠离体胸主动脉条收缩的抑制作用

目的 通过对比观察藏药1号与藏药7号水提液对大鼠离体胸动脉条收缩作用的影响，研究藏药1号与藏药7号的降压机制。方法 以生理盐水作为对照组，观察藏药1号与藏药7号水提液(6mg／ml)和维拉帕米(Ver 0．013 mg／ml)对高K~＋液引起的主动脉条收缩的时效影响，观察对KCl，NE及CaCl_2引起的大鼠主动脉条收缩的量效曲线的影响，以及对NE引起的依赖于细胞内钙及细胞外钙的收缩的影响。结果 藏药1号与藏药7号水提液抑制高K~＋液引起的主动脉收缩(P＜0．001)；而且可以使KCl，NE及CaCl_2引起的大鼠主动脉条收缩的量效曲线非平行右移，最大效应降低，呈非竞争性拮抗作用(P＜0．05)，与维拉帕米相似，并且对NE引起的依赖于细胞内钙及细胞外钙的收缩均有抑制作用(P＜0．05)。从pD'2值分析，藏药1号的药效作用要强于藏药7号，但比Ver的弱。结论 提示藏药1号与藏药7号的降压机制与钙离子通道拮抗剂一致，而且其作用效果比Ver延迟、平缓，其最大作用与Ver相近。而且藏药1号药效更加显著。

重庆城口地区早前寒武系黑色岩系研究：（1）铂族元素成矿潜力评估

重庆城口地区从震旦统到下寒武统发育有丰富的黑色岩系，20世纪末期在该地区黑色岩系中开展了大量的铂族元素（PGE）的找矿工作，但是由于种种原因，关于该地区是否存在PGE矿化异常，还没有得到最终的结论。本次研究在PGE分析方法论证的基础上，进行了大量样品的PGE分析和微量元素分析。主要结论如下：①区域上上震旦统槽区和断块区两套黑色岩系在原始的沉积环境和物源供给上有较大的差异，虽然槽区上震旦统的黑色岩系具有和下寒武统黑色岩系相似但强度较低的V-Cu-Y-Mo—U异常，但基本上不具有明显的PGE-Au-Ag异常。②断块区水井沱组黑色岩系：和平剖面西段新发现的U-V-Mo-PGE异常可能是今后工作的重点，Pt＋Pd最高达248．9×10^-9,局部U-V都达到了工业品位。③槽区巴山组硅质岩：四个剖面都揭示了在硅质岩中广泛存在连续的PGE异常，87个碳质硅质岩平均含Pt＋Pd 57．2×10^-9，有10个样品Pt＋Pd〉100×10^-9，最高达196．5×10^-9；大部分碳质硅质岩都具有不同程度的V-Cu-Y-Mo-Tl-U组合异常，V都达到了独立矿床的品位要求，其中猪草河、燕子河等剖面还存在厚度较大的富矿地段，特别是燕子河剖面，局部还存在REE＋Y的高异常，值得深入研究。④城巴地区下寒武统黑色岩系存在广泛的PGE异常，但没有达到PGE的矿化要求，建议加强该地区的钒矿和铀矿勘探研究，PGE可以综合评价。

The role of mitogen activated protein kinase phosphatase-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons: relevance to Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

Characterisation of the role of canonical BMP-Smad 1/5/8 signalling in the development of ventral midbrain dopaminergic neurons

Ventral midbrain (VM) dopaminergic (DA) neurons, which project to the dorsal striatum via the nigrostriatal pathway, are progressively degenerated in Parkinson’s disease (PD). The identification of the instructive factors that regulate midbrain DA neuron development, and the subsequent elucidation of the molecular bases of their effects, is vital. Such an understanding would facilitate the generation of transplantable DA neurons from stem cells and the identification of developmentally-relevant neurotrophic factors, the two most promising therapeutic approaches for PD. Two related members of the bone morphogenetic protein (BMP) family, BMP2 and growth/differentiation factor (GDF) 5, which signal via a canonical Smad 1/5/8 signalling pathway, have been shown to have neurotrophic effects on midbrain DA neurons both in vitro and in vivo, and may function to regulate VM DA neuronal development. However, the molecular (signalling pathway(s)) and cellular (direct neuronal or indirect via glial cells) mechanisms of their effects remain to be elucidated. The present thesis hypothesised that canonical Smad signalling mediates the direct effects of BMP2 and GDF5 on the development of VM DA neurons. By activating, modulating and/or inhibiting various components of the BMP-Smad signalling pathway, this research demonstrated that GDF5- and BMP2-induced neurite outgrowth from midbrain DA neurons is dependent on BMP type I receptor activation of the Smad signalling pathway. The role of glial cell-line derived neurotrophic factor (GDNF)-signalling, dynamin-dependent endocytosis and Smad interacting protein-1 (Sip1) regulation, in the neurotrophic effects of BMP2 and GDF5 were determined. Finally, the in vitro development of VM neural stem cells (NSCs) was characterised, and the ability of GDF5 and BMP2 to induce these VM NSCs towards DA neuronal differentiation was investigated. Taken together, these experiments identify GDF5 and BMP2 as novel regulators of midbrain DA neuronal induction and differentiation, and demonstrate that their effects on DA neurons are mediated by canonical BMPR-Smad signalling.

Investigating the invasive and cytoprotective properties of the heme binding protein HRG-1 in cancer cells

This thesis investigates the mechanisms by which HRG-1 contributes to the invasive and cytoprotective signalling pathways in cancer cells through its effects on VATPase activity and heme transport. Plasma membrane-localised V-ATPase activity correlates with enhanced metastatic potential in cancer cells, which is attributed to extrusion of protons into the extracellular space and activation of pH-sensitive, extracellular matrix degrading-proteases. We found that HRG-1 is co-expressed with the V-ATPase at the plasma membrane of certain aggressive cancer cell types. Modulation of HRG-1 expression altered both the localisation and activity of the VATPase. We also found that HRG-1 enhances trafficking of essential transporters such as the glucose transporter (GLUT-1) in cancer cells, and increases glucose uptake, which is required for cancer cell growth, metabolism and V-ATPase assembly. Heme is potentially cytotoxic, owing to its iron moiety, and therefore the trafficking of heme is tightly controlled in cells. We hypothesised that HRG-1 is required for the transport of heme to intracellular compartments. Importantly, we found that HRG-1 interacts with the heme oxygenases that are necessary for heme catabolism. HRG-1 is also required for trafficking of both heme-bound and nonheme-bound receptors and suppression of HRG-1 results in perturbed receptor trafficking to the lysosome. Suppression of HRG-1 in HeLa cells increases toxic heme accumulation, reactive oxygen species accumulation, and DNA damage resulting in caspasedependent cell death. Mutation of essential heme binding residues in HRG-1 results in decreased heme binding to HRG-1. Interestingly, cells expressing heme-binding HRG-1 mutants exhibit decreased internalisation of the transferrin receptor compared to cells expressing wildtype HRG-1. These findings suggest that HRG- 1/heme trafficking contributes to a hitherto unappreciated aspect of receptormediated endocytosis. Overall, the findings of this thesis show that HRG-1-mediated regulation of intracellular and extracellular pH through V-ATPase activity is essential for a functioning endocytic pathway. This is critical for cells to acquire nutrients such as folate, iron and glucose and to mediate signalling in response to growth factor activation. Thus, HRG-1 facilitates enhanced metabolic activity of cancer cells to enable tumour growth and metastasis.

Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease.

Neurodegenerative diseases such as Huntington disease are devastating disorders with no therapeutic approaches to ameliorate the underlying protein misfolding defect inherent to poly-glutamine (polyQ) proteins. Given the mounting evidence that elevated levels of protein chaperones suppress polyQ protein misfolding, the master regulator of protein chaperone gene transcription, HSF1, is an attractive target for small molecule intervention. We describe a humanized yeast-based high-throughput screen to identify small molecule activators of human HSF1. This screen is insensitive to previously characterized activators of the heat shock response that have undesirable proteotoxic activity or that inhibit Hsp90, the central chaperone for cellular signaling and proliferation. A molecule identified in this screen, HSF1A, is structurally distinct from other characterized small molecule human HSF1 activators, activates HSF1 in mammalian and fly cells, elevates protein chaperone expression, ameliorates protein misfolding and cell death in polyQ-expressing neuronal precursor cells and protects against cytotoxicity in a fly model of polyQ-mediated neurodegeneration. In addition, we show that HSF1A interacts with components of the TRiC/CCT complex, suggesting a potentially novel regulatory role for this complex in modulating HSF1 activity. These studies describe a novel approach for the identification of new classes of pharmacological interventions for protein misfolding that underlies devastating neurodegenerative disease.

Integrated analysis of CANVAS 1 and 2: phase 3, multicenter, randomized, double-blind studies to evaluate the safety and efficacy of ceftaroline versus vancomycin plus aztreonam in complicated skin and skin-structure infection.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of complicated skin and skin-structure infection (cSSSI). Increasing antimicrobial resistance in cSSSI has led to a need for new safe and effective therapies. Ceftaroline was evaluated as treatment for cSSSI in 2 identical phase 3 clinical trials, the pooled analysis of which is presented here. The primary objective of each trial was to determine the noninferiority of the clinical cure rate achieved with ceftaroline monotherapy, compared with that achieved with vancomycin plus aztreonam combination therapy, in the clinically evaluable (CE) and modified intent-to-treat (MITT) patient populations. METHODS: Adult patients with cSSSI requiring intravenous therapy received ceftaroline (600 mg every 12 h) or vancomycin plus aztreonam (1 g each every 12 h) for 5-14 days. RESULTS: Of 1378 patients enrolled in both trials, 693 received ceftaroline and 685 received vancomycin plus aztreonam. Baseline characteristics of the treatment groups were comparable. Clinical cure rates were similar for ceftaroline and vancomycin plus aztreonam in the CE (91.6% vs 92.7%) and MITT (85.9% vs 85.5%) populations, respectively, as well as in patients infected with MRSA (93.4% vs 94.3%). The rates of adverse events, discontinuations because of an adverse event, serious adverse events, and death also were similar between treatment groups. CONCLUSIONS: Ceftaroline achieved high clinical cure rates, was efficacious against cSSSI caused by MRSA and other common cSSSI pathogens, and was well tolerated, with a safety profile consistent with the cephalosporin class. Ceftaroline has the potential to provide a monotherapy alternative for the treatment of cSSSI. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00424190 for CANVAS 1 and NCT00423657 for CANVAS 2.