bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of poly(vinyl acetate) on structures and properties of PbZr0.52Ti0.48O3 thick films
Authors: Lin Peng , Ren Wei , Wu Xiaoqing , Shi Peng , Yan Xin , Yao Xi
Published: October 2007

Pb Zr 0.52 Ti 0.48 O 3 (PZT) thick films are prepared by a polymer-assisted metallo-organic compound decomposition process. The addition of a polymer, poly(vinyl acetate) (PVAc), in PZT precursor solutions promotes the formation of the perovskite phase. Meanwhile, the crack formation is effectively suppressed. The single-layer thickness of PZT films increases from 0.07to0.22μm. It is found that PZT recrystallizes after the PVAc-related organic compounds are decomposed. Nanosized pores are observed in the morphological surfaces of PZT thick films. The crack-free PZT thick films with thickness of 1.3μm by the repeated deposition exhibit good electrical properties with dielectric constant of 996, dielectric loss around of 3%, remanent polarization of 36.3μC∕cm2, and coercive field of 78.5kV∕cm, which are potential candidates for microelectromechanical system (MEMS) applications.
Spin injection due to interfacial spin asymmetry in a ferromagnet-semiconductor hybrid structure
Authors: Bala Kumar S. , Tan S. G. , Jalil M. B. A. , Jiang Yong
Published: October 2007

We have shown analytically that interfacial resistance, interfacial spin asymmetry, and therefore spin injection in a ferromagnetic-semiconductor-ferromagnetic condensed matter system are coupled to the spatially varying electrochemical potential. Our finding has technological significance because it implies spin injection sensitivity to external electrical bias. We show that as current density increases, spin asymmetry and the magnitude of interfacial resistance reduces, resulting in lower spin injection. We conclude that to increase spin injection, it is necessary to increase the intrinsic spin selectivity of the interfacial barriers.
Fast drift Alfvén waves excited at the low-frequency band in tokamak plasmas
Authors: Elfimov A. G. , Pires C. J. A. , Galvão R. M. O.
Published: October 2007

It is shown that fast drift Alfvén waves can be excited in tokamak plasmas by an external antenna operating in the low-frequency band. The dispersion of these waves depends on the derivative of the q-profile or drift terms in the case of low or negative shear. The wave absorption is determined by the Alfvén continuum dissipation and has an oscillating increase with frequency. Typical global Alfvén wave resonances are found at the plasma core for different signs of poloidal/toroidal mode numbers (N∕M<0) for a standard tokamak safety factor profile with central value q0>1.
Photoinduced charge transfer between poly(3-hexylthiophene) and germanium nanowires
Authors: Du Pasquier Aurelien , Mastrogiovanni Daniel D. T. , Klein Lauren A. , Wang Tong , Garfunkel Eric
Published: October 2007

Germanium nanowires (GeNWs) were used to enhance the properties of organic photovoltaic devices. GeNWs were grown to a length of 1–5μm on SiO2 by the vapor-liquid-solid method catalyzed by 20nm Au seeds. Once grown, the GeNWs were dispersed in solution with poly(3-hexylthiophene) and spin cast into films. The photoluminescence and external quantum efficiency of the films indicated a significant increase in exciton dissociation and photocurrent generation. The results imply that the GeNWs may act as an electron acceptor for bulk heterojunction hybrid-inorganic/organic photovoltaic devices. The impacts of GeNW on device characteristics are discussed.
Enhanced chemical shift of carbon nanotube from laser assisted gas incorporation
Authors: Chuang Cheng-Hao , Chen Chia-Hao , Chang Yin-Ming , Peng Chih-Wei , Wong Sheng-Syun , Tzeng Shien-Der , Gwo Shangjr , Zhu Yanwu , Sow Chorng-Haur , Lin Minn-Tsong
Published: October 2007

We investigate the position-selected electronic structure of laser modified carbon nanotubes (CNTs) by scanning photoelectron microscopy. After laser pruning removed the top layer of CNTs in air and N2 environment, the modified region shows enhanced chemical shifts of 0.9 and 0.6eV in carbon 1s state, respectively. The modification of electronic structure is shown to be strongly dependent on the gaseous environment. We demonstrate an effective postgrowth process to modify the electronic structure of CNTs for further applications.
Quantum-confined Stark effects in the m-plane In0.15Ga0.85N∕GaN multiple quantum well blue light-emitting diode fabricated on low defect density freestanding GaN substrate
Authors: Onuma T. , Amaike H. , Kubota M. , Okamoto K. , Ohta H. , Ichihara J. , Takasu H. , Chichibu S. F.
Published: October 2007

Quantum-confined Stark effects (QCSEs) in a polarization-free m-plane In0.15Ga0.85N∕GaN multiple quantum well (MQW) blue light-emitting diode fabricated on the low defect density (DD) freestanding GaN substrate were investigated. The electroluminescence (EL) peak at 2.74eV little shifted to the higher energy with the increase in current because of the absence of the polarization fields. The effective radiative lifetime increased and the nonradiative lifetime decreased with the increase in the junction field, and the results were quantitatively explained in terms of field-induced QCSE including tunneling escape of holes from the MQW. As a result of the use of the low DD substrate, the equivalent internal quantum efficiency, which was approximated as the spectrally integrated EL intensity at 300K divided by that at 150K, of 43% was achieved.
Partitioning of salt ions in FT30 reverse osmosis membranes
Authors: Zhang Xijing , Cahill David G. , Coronell Orlando , Mariñas Benito J.
Published: October 2007

FT30 membranes consist of a polyamide active layer interfacially polymerized on a porous polysulfone support. The ion partition coefficient κ in the active layer is a key thermodynamic parameter that partially controls the ability of the membrane to desalinate water. Membranes are soaked in aqueous solutions of CsCl, KBr, or Na2WO4 with salt concentrations of 0.002M<Cs<2M, freeze dried to remove water without disturbing ion distribution, and analyzed by Rutherford backscattering spectrometry. For Cs<0.01M, κ is surprisingly large and independent of Cs, κ=6±2. The porosity ϕ of the top 500nm of the support layer is also extracted from the RBS data: ϕ=0.45±0.05.
Resistive switching effect in SrTiO3−δ∕Nb-doped SrTiO3 heterojunction
Authors: Ni M. C. , Guo S. M. , Tian H. F. , Zhao Y. G. , Li J. Q.
Published: October 2007

The authors report on the fabrication and properties of SrTiO3−δ∕Nb-doped SrTiO3 heterojunctions. The current-voltage curves of these junctions show hysteresis and remarkable resistive switching behavior. Hysteresis was also observed in the capacitance-voltage curves of these junctions. Upon applying voltage pulses, the resistance of the heterojunctions can be switched between different states and the relaxation of the junction current after switching follows the Curie–Von Schweidler law. The results were discussed by considering the role of defects in the interfacial depletion region of the heterojunctions. This work indicates that heterojunctions composed of two oxides can also show the switching effect, which is useful for applications.
Janus balance of amphiphilic colloidal particles
Authors: Jiang Shan , Granick Steve
Published: October 2007

We introduce the notion of “Janus balance” (J), defined as the dimensionless ratio of work to transfer an amphiphilic colloidal particle (a “Janus particle”) from the oil-water interface into the oil phase, normalized by the work needed to move it into the water phase. The J value can be calculated simply from the interfacial contact angle and the geometry of Janus particles, without the need to know the interfacial energy. It is demonstrated that Janus particles of the same chemical composition but different geometries will have the highest adsorption energy when J=1. Even for particles of homogeneous chemical makeup, the Janus balance concept can be applied when considering the contact angle hysteresis in desorbing the particle from equilibrium into the water or oil phase. The Janus balance concept may enable predictions of how a Janus particle behaves with respect to efficiency and function as a solid surfactant, as the Janus balance of solid surfactants is the analog of the classical hydrophile-lipophile balance of small surfactant molecules.
On the role of oxygen in dielectric barrier discharge actuation of aerodynamic flows
Authors: Kim W. , Do H. , Mungal M. G. , Cappelli M. A.
Published: October 2007

Phase-locked particle image velocimetry is used to study the mechanism of induced flow in the near field of a rf dielectric barrier discharge actuator mounted in the separated flow region of a bluff body. Flow actuation is found to be asymmetric, with suction toward the buried downstream electrode when it is biased positively relative to the upstream exposed electrode. Lesser flow is seen on the reverse voltage swing, where the buried electrode should attract positive ions. This phenomenon is enhanced when oxygen is added to the flow, suggesting that oxygen negative ions, possibly O2−, play a dominant role in plasma actuation.
Infrared thermal emission in macroporous silicon three-dimensional photonic crystals
Authors: Garín M. , Trifonov T. , Rodríguez A. , Alcubilla R.
Published: October 2007

In this paper we investigate the infrared thermal emission properties of macroporous silicon with modulated pore diameter. Samples with different pore modulation periodicities but fixed in-plane lattice constant are fabricated. Normal emission of these samples is measured between 373 and 673K. Room-temperature normal-incidence reflectance and transmission spectra are also measured and compared with the photonic band structure simulation. It is shown that thermal emission is suppressed due to photonic band gap effect along the pore axis in excellent agreement with the numerical calculations.
Growing extremely thin bulklike metal film on a semiconductor surface: Monolayer Al(111) on Si(111)
Authors: Jiang Ying , Kim Yong-Hyun , Zhang S. B. , Ebert Philipp , Yang Shenyuan , Tang Zhe , Wu Kehui , Wang E. G.
Published: October 2007

We report combined scanning tunneling microscopy, x-ray photoelectron emission spectroscopy, electron energy loss spectroscopy, and theoretical study of the growth of ultrathin Al film on the Si(111) substrate. We show that by (i) a modification of the substrate reconstruction with a 3×3 surface and (ii) a choice of materials with commensurate lattices, atomically flat film can be obtained even at the ultimate one monolayer limit, while maintaining a bulklike atomic structure. Detailed analysis shows that this monolayer Al(111)-1×1 film is electronically decoupled from the Si substrate, and it shows metallic characteristics.
ZnO-based thin film transistors having high refractive index silicon nitride gate
Authors: Remashan K. , Jang J. H. , Hwang D. K. , Park S. J.
Published: October 2007

The effect of properties of silicon nitride films on the electrical performance of zinc oxide (ZnO) thin film transistors (TFTs) has been investigated by utilizing silicon nitride films having refractive indices of 2.45 and 1.85. The ZnO TFTs having a silicon nitride with a high refractive index of 2.45 exhibited a field effect mobility of 8cm2∕Vs, on/off current ratio of 106, and subthreshold slope of 0.9V/decade. On the other hand, TFTs having a silicon nitride with a low refractive index of 1.85 showed a field effect mobility of 0.5cm2∕Vs, on/off current ratio of less than 102, and subthreshold slope of 19V/decade. The improved device performance was ascribed to a better interface between ZnO and high refractive index silicon nitride, and hydrogenation of the ZnO channel with the hydrogen originated from the high refractive index silicon nitride.
Global Oil Production: Forecasts and Methodologies
Authors: Bentley Roger , Boyle Godfrey
Published: October 2007

A range of forecasts of global oil production made between 1956 and the present day are listed. For the majority of these the methodology used to generate the forecast is described. The paper distinguishes between three types of forecast: group 1—quantitative analyses which predict that global oil production will reach a resource-limited peak in the near term, and certainly before the year 2020; group 2—forecasts that use quantitative methods, but which see no production peak within the forecast's time horizon (typically 2020 or 2030); group 3—nonquantitative analyses that rule out a resource-limited oil peak within the foreseeable future. The paper analyses these forecast types and suggests that group 1 forecasts are the most realistic.
Acting in the Network: ANT and the Politics of Generating Associations
Authors: Routledge Paul
Published: October 2007

In this paper I will draw upon ANT to consider how political associations are generated within a global network of grassroots peasant movements. ANT has failed to fully consider the ways of generating such associations, especially the processes through which such associations are made. In so doing, the causes of and accountability for differential power relations have been precluded, as have the productive dimensions of that power. Through a consideration of the moments and strategies of network translation, I will show that power inequalities and intentionality act to determine the contours of network association.
Altering systemic acid - base balance through nutrition failed to change secondary sex ratio
Authors: Roche John R. , Lee Julia M.
Published: October 2007

There is evidence that differences in either maternal blood pH or dietary mineral content can result in alterations in secondary sex ratio in mammals. Altering the proportions of certain dietary minerals is known to influence blood pH, offering a possible explanation for this effect of diet on secondary sex ratio. The present study was performed to investigate whether altering blood pH by manipulating the dietary cation–anion difference (DCAD) would alter secondary sex ratio. The DCAD is calculated (in mEq per 100 g dry matter) as the difference between metabolically strong cations (Na + K) and metabolically strong anions (Cl + S) in the diet. Three hundred female mice were randomly allocated to either a low or high DCAD ration for 3 weeks before coitus. Urine pH was monitored before beginning the experiment, as well as before and after the breeding period, as a proxy for blood pH. Mice on the low DCAD diet had a lower urine pH (mean (± s.d.) 6.0 ± 0.1) than mice on the high DCAD diet (8.2 ± 0.6), but DCAD did not affect the percentage of mice that became pregnant, the number of offspring per pregnant mouse or the sex ratio of the neonate group. These results suggest that blood pH alone does not alter sex ratio and that an altered systemic pH is not the reason for reported mineral-related variations in sex ratio.
Caspase-3-mediated apoptosis and cell proliferation in the equine endometrium during the oestrous cycle
Authors: Roberto da Costa R. P. , Serrão P. M. , Monteiro S. , Pessa P. , Silva J. Robalo , Ferreira-Dias G.
Published: October 2007

Cell proliferation and apoptosis are hormone-dependent physiological processes involved in endometrial growth and regression. The aims of the present study were: (1) to evaluate endometrial cell proliferation using proliferating cell nuclear antigen (PCNA) expression; (2) to evaluate the induction of endometrial cell death by the expression of active caspase-3 and the apoptotic phenotype visualised by DNA fragmentation; and (3) to relate these observations to endometrial tissue dynamics in the equine endometrium throughout the oestrous cycle. Endometria were assigned to follicular and luteal phases based on ovarian structures and plasma progesterone. Cell proliferation and active caspase-3-mediated apoptosis were expressed in both phases of the oestrous cycle. In the luteal phase, PCNA expression was higher than in the follicular phase. Highest PCNA activity was noted in the luminal and glandular structures. Active caspase-3 staining was increased in luminal epithelium and deep glandular cells during the luteal phase. However, in the follicular phase, stromal cells showed greater active caspase-3 expression. Only a few apoptotic endometrial cells were detected by terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) and these cells were mostly present in luminal and glandular structures. A simultaneous increase in DNA, cell proliferation and protein synthesis was observed in the endometrium during the mid-luteal phase. This suggests that cell hyperplasia occurs at the time the histotroph is needed for eventual embryo nourishment.
Emergency prevention of extinction of a transgenic allele in a less-fertile transgenic mouse line by crossing with an inbred or outbred mouse strain coupled with assisted reproductive technologies
Authors: Mayer Anna , Bulian Diana , Scherb Hagen , Hrabé de Angelis Martin , Schmidt Jörg , Mahabir Esther
Published: October 2007

Certain transgenic mouse lines are difficult to breed or archive and, consequently, their transgenes become lost. We examined a C57BL/6 mouse line (B6-tg), transgenic for green fluorescent protein (GFP) with low fertility, and its crosses with the more prolific inbred C3HeB/FeJ (C3) and outbred Swiss (SW) strains in order to assess the possibility of emergency prevention of extinction of a transgenic allele by using assisted reproductive technologies (ART). Out-crossing was performed by natural mating or in vitro fertilisation (IVF) with heterozygous mice. Most of the crossing combinations resulted in improved archiving and rederivation efficiencies of the transgenic allele. Natural crossing increased both mean litter size by two to three pups and the superovulatory rate from 69% for B6-tg to 70–90% for females from the out-crosses. Each plug-positive B6-tg female yielded an average of 4.6 two-cell embryos, whereas females from the out-crosses produced three- to fivefold that amount. After thawing, 13% of B6-tg embryos and 6–12% of out-crossed embryos developed into transgenic pups after transfer into recipients. After IVF with cryopreserved spermatozoa, cleavage rates were 4% for B6-tg, 22–37% for B6-tg oocytes out-crossed with C3 and SW spermatozoa, 9–49% for gametes from out-crossed mice and 28–44% for back-crosses with B6 oocytes. Transgenic pups were not derived from IVF with B6-tg gametes when either fresh or cryopreserved spermatozoa were used. Rederivation efficiencies were 7% and 4% from out-crosses of B6-tg oocytes with C3 and SW spermatozoa, respectively, 6–22% for gametes from out-crossed mice and 4–10% for the back-crosses. Although out-crossing changes the original genetic background, the strategy of crossing coupled with ART prevents the extinction of an allele of interest, especially where archiving and rederivation of the transgenic line fail.
Sympathetic pharmacological denervation in ageing rats: effects on ovulatory response and follicular population
Authors: Chávez-Genaro Rebeca , Lombide Paula , Domínguez Roberto , Rosas Patricia , Vázquez-Cuevas Francisco
Published: October 2007

The present study analyses the participation of ovarian innervation during reproductive senescence. We use the model of acute peripheral pharmacological sympathetic denervation with guanethidine in young (3 months old), middle-aged (12 months old) or old (18 months old) rats with spontaneous or induced ovulation. Ovarian levels of norepinephrine (NE) were measured by HPLC and the oestrous cycle, the number of ovulating animals and the percentage of atretic follicles were also assessed. Aged animals showed a progressive reduction in ovulatory capacity and an increase in ovarian NE content. Acute denervation increased the percentage of healthy follicles in 12- and 18-month-old rats compared with control adult animals. Combined treatment of denervation plus stimulation with gonadotrophins doubled the number of ova shed in young adult rats and restablished a partial ovulation in 12-month-old rats. The results suggest that ovarian noradrenergic innervation plays a modulator role in ovarian physiology during the ageing ovary process. The action of ovarian noradrenergic innervation seems to be associated with folliculogenesis and the ovarian response to gonadotrophins.
Enzymatic removal of asparagine-linked carbohydrate chains from heterodimer human chorionic gonadotrophin and effect on bioactivity
Authors: Richard Craig A. H. , Creinin Mitchell D. , Kubik Carolyn J. , DeLoia Julie A.
Published: October 2007

The native form of human chorionic gonadotropin (hCG) is a heterodimer protein with two asparagine (Asn)-linked carbohydrate chains on each subunit. Removal of the Asn-linked carbohydrate chains from hCG has resulted in hCG variants with consistent antagonistic properties on isolated murine cells. Specific and direct enzymatic removal of these carbohydrate chains from native hCG with resultant antagonistic properties has not been reported. An antagonist to the hCG/luteinising hormone (LH) receptor could be used as an anticancer therapy, emergency contraceptive or for therapeutic resolution of ectopic pregnancies. Therefore, our aim was to use enzymes to specifically remove Asn-linked carbohydrate chains from hCG in the heterodimer form and analyse the resultant bioactivity. Native hCG was treated with endoglycosidases, carbohydrate removal was analysed with electrophoresis and the hCG variants were tested for altered bioactivity with human and murine cells. Endoglycosidases were able to cleave most of the Asn-linked carbohydrate chains from the native hCG. The deglycosylated hCG demonstrated a 75% reduction in bioactivity on a murine Leydig cell line and a 65% reduction in bioactivity on human granulosa cells. These results exemplify a simple and efficient method for creating deglycosylated hCG and provide the most direct evidence for the importance of Asn-linked carbohydrate chains in maintaining hCG bioactivity.
Effect of GnRH treatment on the maturation and in vitro development of oocytes collected from 4- to 6-week-old Merino lambs
Authors: Kelly Jennifer M. , Kleemann David O. , Maxwell W. M. Chis , Walker Simon K.
Published: October 2007

Two experiments were conducted in Merino lambs to examine the effects of gonadotrophin-releasing hormone (GnRH) treatment on the developmental competence of oocytes collected after pretreatment with follicle stimulating hormone (FSH). The first experiment examined the effects of six GnRH treatment times (control and GnRH administered 2, 4, 6, 8 and 10 h before oocyte collection) and four in vitro maturation (IVM) periods (18, 20, 22, 24 h) on the rate of oocyte nuclear maturation. The second experiment examined the effect of five GnRH treatment times (control and GnRH administered 2, 4, 6 and 8 h before oocyte collection) and three IVM periods (20, 22, 24 h) on the development of oocytes and embryos after in vitro maturation, fertilisation and culture. In Experiment 1, GnRH treatment did not influence the mean number of cumulus-oocyte-complexes (COCs) collected or COC morphology at the time of collection. However, treatment changed (P < 0.01) the distribution of follicle size and this was primarily due to a marked reduction in the number of follicles with diameters <2 mm. In addition, GnRH treatment at 6 and 8 h increased (P < 0.01) the proportion of oocytes that developed to Metaphase II (MII) (63.2 and 72.6%, respectively) compared with other treatment times (range 52.9–59.9%). Nuclear maturation was influenced by a significant (P < 0.05) interaction between GnRH treatment and IVM period due to a disproportionately greater number of oocytes at the germinal vesicle breakdown (GVBD) stage for the 2 and 4 h GnRH treatments compared with other treatments. In Experiment 2, cleavage rate (range 63.5–85.9%) was highest when GnRH was administered 8 h before collection but the percentage of cleaved oocytes that developed into blastocysts (range 10.0–35.0%) was significantly (P < 0.05) lower for the 6 and 8 h GnRH treatments compared with the control and the 2 h GnRH treatment. These results demonstrate that GnRH treatment before oocyte collection can improve nuclear maturation and cleavage rates in lamb oocytes but that these improvements are not reflected in improved rates of blastocyst development. It is speculated that this discrepancy may result from GnRH treatment either adversely affecting cytoplasmic maturation or inducing asynchrony between the maturation of the nuclear and cytoplasmic components of the oocyte.
Perturbed growth and development in marsupial young after reciprocal cross-fostering between species
Authors: Menzies Brandon R. , Shaw Geoff , Fletcher Terry P. , Renfree Marilyn B.
Published: October 2007

Cross-fostering of marsupial young between species can potentially facilitate propagation of endangered or rare marsupial species by artificially increasing the number of progeny produced. The present study compares the growth and development of normal and cross-fostered tammar and parma wallabies. Tammars cross-fostered into the pouches of parmas grew at a similar rate to naturally reared tammar young and had developmental milestones at a similar age. However, parma young cross-fostered between the day of birth and 15 days post-partum into tammars that were carrying young of equivalent developmental stages did not grow normally and were lost from the pouch. Parma young cross-fostered at 30 days survived, but had significantly reduced growth rates and their developmental milestones were delayed compared with normally reared parma young. Thus, growth can be affected by cross-fostering, even between species like tammars and parmas that are of similar size and have similar lactation lengths. The results of the present study suggest that maternal milk regulates the timing of development of each species and a mis-match in the time that each young receives critical milk components can have a marked effect on their growth and development.
A functional genetic screen identifies retinoic acid signaling as a target of histone deacetylase inhibitors
Authors: Epping Mirjam T. , Wang Liming , Plumb Jane A. , Lieb Michele , Gronemeyer Hinrich , Brown Robert , Bernards René
Published: October 2007

Understanding the pathways that are targeted by cancer drugs is instrumental for their rational use in a clinical setting. Inhibitors of histone deacetylases (HDACI) selectively inhibit proliferation of malignant cells and are used for the treatment of cancer, but their cancer selectivity is understood poorly. We conducted a functional genetic screen to address the mechanism(s) of action of HDACI. We report here that ectopic expression of two genes that act on retinoic acid (RA) signaling can cause resistance to growth arrest and apoptosis induced by HDACI of different chemical classes: the retinoic acid receptor α (RARα) and preferentially expressed antigen of melanoma (PRAME), a repressor of RA signaling. Treatment of cells with HDACI induced RA signaling, which was inhibited by RARα or PRAME expression. Conversely, RAR-deficient cells and PRAME-knockdown cells show enhanced sensitivity to HDACI
in vitro
and in mouse xenograft models. Finally, a combination of RA and HDACI acted synergistically to activate RA signaling and inhibit tumor growth. These experiments identify the RA pathway as a rate-limiting target of HDACI and suggest strategies to enhance the therapeutic efficacy of HDACI.
Mutations as trapdoors to two competing native conformations of the Rop-dimer
Authors: Schug Alexander , Whitford Paul C. , Levy Yaakov , Onuchic José N.
Published: October 2007

Conformational transitions play a central role in regulating protein function. Structure-based models with multiple basins have been used to understand the mechanisms governing these transitions. A model able to accommodate multiple folding basins is proposed to explore the mutational effects in the folding of the Rop-dimer (Rop). In experiments, Rop mutants show unusually strong increases in folding rates with marginal effects on stability. We investigate the possibility of two competing conformations representing a parallel (P) and the wild-type antiparallel (AP) arrangement of the monomers as possible native conformations. We observe occupation of both distinct states and characterize the transition pathways. An interesting observation from the simulations is that, for equivalent energetic bias, the transition to the P basin (non-wild-type basin) shows a lower free-energy barrier. Thus, the rapid kinetics observed in experiments appear to be the result of two competing states with different kinetic behavior, triggered upon mutation by the opening of a trapdoor arising from Rop's symmetric structure. The general concept of having competing conformations for the native state goes beyond explaining Rop's mutational behaviors and can be applied to other systems. A switch between competing native structures might be triggered by external factors to allow, for example, allosteric control or signaling.
Quantum dots provide an optical signal specific to full collapse fusion of synaptic vesicles
Authors: Zhang Qi , Cao Yu-Qing , Tsien Richard W.
Published: October 2007

Synaptic vesicles are responsible for releasing neurotransmitters and are thus essential to brain function. The classical mode of vesicle recycling includes full collapse of the vesicle into the plasma membrane and clathrin-mediated regeneration of a new vesicle. In contrast, a nonclassical mode known as “kiss-and-run” features fusion by a transient fusion pore without complete loss of vesicle identity and offers possible advantages for increasing the throughput of neurotransmission. Studies of vesicular traffic have benefited greatly from fluorescent probes like FM dyes and synaptopHluorin. However, intrinsic properties of these probes limit their ability to provide a simple and precise distinction between classical and nonclassical modes. Here we report a novel optical probe specific to full collapse fusion, capitalizing on the size and superior photo-properties of photoluminescent quantum dots (Qdots). Qdots with exposed carboxyl groups were readily taken up by synaptic vesicles in an activity-, Ca
2+
-, and clathrin-dependent manner. Electron microscopy showed that Qdots were harbored within individual vesicles in a 1:1 ratio. The release of Qdots was activity- and Ca
2+
-dependent, similar to FM dyes. As artificial cargo, ≈15 nm in diameter, Qdots will not escape vesicles during kiss-and-run but only with full collapse fusion. Strikingly, Qdots unloaded with kinetics substantially slower than destaining of FM dye, indicating that full-collapse fusion contributed only a fraction of all fusion events. As a full-collapse–fusion-responsive reporter, Qdots will likely promote better understanding of vesicle recycling at small CNS nerve terminals.
Phylogenetic analyses of behavior support existence of culture among wild chimpanzees
Authors: Lycett Stephen J. , Collard Mark , McGrew William C.
Published: October 2007

Culture has long been considered to be not only unique to humans, but also responsible for making us qualitatively different from all other forms of life. In recent years, however, researchers studying chimpanzees (
Pan troglodytes
) have challenged this idea. Natural populations of chimpanzees have been found to vary greatly in their behavior. Because many of these interpopulation differences cannot be readily explained by ecological factors, it has been argued that they result from social learning and, therefore, can be regarded as cultural variations. Recent studies showing social transmission in captive chimpanzee populations suggest that this hypothesis is plausible. However, the culture hypothesis has been questioned on the grounds that the behavioral variation may be explained at a proximate level by genetic differences between subspecies. Here we use cladistic analyses of the major cross-site behavioral data set to test the hypothesis that the behavioral differences among the best-documented chimpanzee populations are genetically determined. If behavioral diversity is primarily the product of genetic differences between subspecies, then population data should show less phylogenetic structure when data from a single subspecies (
P. t. schweinfurthii
) are compared with data from two subspecies (
P. t. verus
and
P. t. schweinfurthii
) analyzed together. Our findings are inconsistent with the hypothesis that the observed behavioral patterns of wild chimpanzee populations can be explained primarily by genetic differences between subspecies. Instead, our results support the suggestion that the behavioral patterns are the product of social learning and, therefore, can be considered cultural.
Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability
Authors: Pentcheva-Hoang Tsvetelina , Chen Lieping , Pardoll Drew M. , Allison James P.
Published: October 2007

Despite the importance of programmed death-1 (PD-1) for T cell inhibition, little is known about its intracellular trafficking or requirements for localization to the immunological synapse. Here, we show that in activated T cells, PD-1 is present at the plasma membrane, near the Golgi and in the trans-Golgi network. Unlike CD28 and CTLA-4, PD-1 accumulation at the synapse is extensive only when T cells interact with dendritic cells (DCs) expressing high B7-DC levels. However, B7-H1 is also critically important, especially when the DCs have little B7-DC. Despite this preference, B7-H1
−/−
DCs elicit greater cytokine secretion than B7-DC
−/−
DCs during T cell restimulation, possibly because they also express less B7-DC. PD-1 and CD28 have similar kinetics of synaptic accumulation, suggesting that the process involves T cell receptor-triggered cytoskeletal reorganization followed by ligand binding.
Understanding cisplatin resistance using cellular models
Authors: Stordal Britta , Davey Mary
Published: October 2007

Many mechanisms of cisplatin resistance have been proposed from studies of cellular models of resistance including changes in cellular drug accumulation, detoxification of the drug, inhibition of apoptosis and repair of the DNA adducts. A series of resistant models were developed from CCRF‐CEM leukaemia cells with increasing doses of cisplatin from 100 ng/ml. This produced increasing resistance up to 7‐fold with a treatment dose of 1.6 μg/ml. Cisplatin resistance in these cells correlated with increases in the antioxidant glutathione, yet treatment with buthionine sulphoximine, an inhibitor of glutathione synthesis, had no effect on resistance, suggesting that the increase in glutathione was not directly involved in cisplatin resistance. Two models were developed from H69 SCLC cells, H69‐CP and H69CIS200 using 100 ng/ml or 200 ng/ml cisplatin respectively. Both cell models were 2‐4 fold resistant to cisplatin, and have decreased expression of p21 which may increase the cell's ability to progress through the cell cycle in the presence of DNA damage. Both the H69‐CP and H69CIS200 cells showed no decrease in cellular cisplatin accumulation. However, the H69‐CP cells have increased levels of cellular glutathione and are cross resistant to radiation whereas the H69CIS200 cells have neither of these changes. This suggests that increases in glutathione may contribute to cross‐resistance to other drugs and radiation, but not directly to cisplatin resistance. There are multiple resistance mechanisms induced by cisplatin treatment, even in the same cell type. How then should cisplatin‐resistant cancers be treated? Cisplatin‐resistant cell lines are often more sensitive to another chemotherapeutic drug paclitaxel (H69CIS200), or are able to be sensitized to cisplatin with paclitaxel pre‐treatment (H69‐CP). The understanding of this sensitization by paclitaxel using cell models of cisplatin resistance will lead to improvements in the clinical treatment of cisplatin resistant tumours. IUBMB Life, 59: 696‐699, 2007
Sirolimus Inhibits Human Pancreatic Carcinoma Cell Proliferation by a Mechanism Linked to the Targeting of mTOR/HIF‐1 Alpha/VEGF Signaling
Authors: Wang Yu , Zhao Qiu , Ma Songlin , Yang Fang , Gong Yong , Ke Changshu
Published: October 2007

Sirolimus(SRL, Rapamuneâ, rapamycin) is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus exerts its biological activity by inhibiting the serine‐threonine kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. The ability of sirolimus to inhibit cancer cell proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anticancer agents. Here, we made mTOR as a controlling target, using a new immunosuppressant named sirolimus, to investigate the inhibitory effects of sirolimus on cell proliferation and the expression of mTOR, Hypoxia‐inducible factor‐1 alpha(HIF‐1α) and vascular endothelial growth factor (VEGF) in human pancreatic carcinoma SW1990 cell line. Sirolimus is effective in vivo against pancreatic carcinoma and demonstrates that the effect of sirolimus on the inhibition of tumor cell proliferation is associated with the suppression of the mTOR/HIF‐1α/vascular endothelial growth factor (VEGF) pathway. Thus, the targeting of mTOR signaling has been exploited as a novel therapy for human cancers. IUBMB Life, 59: 717‐721, 2007
Vitamin B12 Transport Proteins: Crystallographic Analysis of β‐axial Ligand Substitutions in Cobalamin Bound to Transcobalamin
Authors: Wuerges Jochen , Geremia Silvano , Fedosov Sergey N. , Randaccio Lucio
Published: October 2007

Cobalamin (Cbl, vitamin B12) is an essential micronutrient that is synthesized only by bacteria. Mammals have developed a complex system for internalization of this vitamin from the diet. Three binding proteins (haptocorrin, intrinsic factor, transcobalamin (TC)) and several specific cell surface receptors are involved in the process of intestinal absorption, plasma transport and cellular uptake. The recent literature on the binding proteins is briefly reviewed. A structural study is presented addressing a unique feature of TC among the three proteins, i.e., the displacement of the weak Co(III)‐ligand H2O at the upper (or β) axial side of H2O‐Cbl by a histidine side chain. We have investigated crystallographically the β‐ligand exchange on Cbl bound to TC by crystallization of bovine holo‐TC in the presence of either cyanide or sulfite. The resulting electron density maps show that the histidine side chain has been displaced by an exogenous ligand CN‐ or to a lower extent than expected based on their higher affinity for Co and excess concentration with respect to histidine. This may reflect either reduced affinities of CN‐ and or the advantageous binding of the protein‐integrated His‐residue when competing for the β‐site of Cbl bound to TC. The loop hosting the histidine residue appears more flexible after disruption of the coordination bond His‐Cbl but no other differences are observed in the overall structure of holo‐TC. These structural results are discussed in relation to a possible physiological role of histidine substitution for H2O and regarding the role of β‐conjugated Cbl‐analogues recently proposed for targeted delivery of imaging agents. IUBMB Life, 59: 722‐729, 2007
A conserved CaM- and radial spoke–associated complex mediates regulation of flagellar dynein activity
Authors: Dymek Erin E. , Smith Elizabeth F.
Published: October 2007

For virtually all cilia and eukaryotic flagella, the second messengers calcium and cyclic adenosine monophosphate are implicated in modulating dynein- driven microtubule sliding to regulate beating. Calmodulin (CaM) localizes to the axoneme and is a key calcium sensor involved in regulating motility. Using immunoprecipitation and mass spectrometry, we identify members of a CaM-containing complex that are involved in regulating dynein activity. This complex includes flagellar-associated protein 91 (FAP91), which shares considerable sequence similarity to AAT-1, a protein originally identified in testis as an A-kinase anchor protein (AKAP)– binding protein. FAP91 directly interacts with radial spoke protein 3 (an AKAP), which is located at the base of the spoke. In a microtubule sliding assay, the addition of antibodies generated against FAP91 to mutant axonemes with reduced dynein activity restores dynein activity to wild-type levels. These combined results indicate that the CaM- and spoke-associated complex mediates regulatory signals between the radial spokes and dynein arms.
The disulfide relay system of mitochondria is connected to the respiratory chain
Authors: Bihlmaier Karl , Mesecke Nikola , Terziyska Nadia , Bien Melanie , Hell Kai , Herrmann Johannes M.
Published: October 2007

All proteins of the intermembrane space of mitochondria are encoded by nuclear genes and synthesized in the cytosol. Many of these proteins lack presequences but are imported into mitochondria in an oxidation-driven process that relies on the activity of Mia40 and Erv1. Both factors form a disulfide relay system in which Mia40 functions as a receptor that transiently interacts with incoming polypeptides via disulfide bonds. Erv1 is a sulfhydryl oxidase that oxidizes and activates Mia40, but it has remained unclear how Erv1 itself is oxidized. Here, we show that Erv1 passes its electrons on to molecular oxygen via interaction with cytochrome c and cytochrome c oxidase. This connection to the respiratory chain increases the efficient oxidation of the relay system in mitochondria and prevents the formation of toxic hydrogen peroxide. Thus, analogous to the system in the bacterial periplasm, the disulfide relay in the intermembrane space is connected to the electron transport chain of the inner membrane.
Reduced receptor editing in lupus-prone MRL/lpr mice
Authors: Lamoureux Jennifer L. , Watson Lisa C. , Cherrier Marie , Skog Patrick , Nemazee David , Feeney Ann J.
Published: October 2007

The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity.
Drosophila Bestrophin-1 Chloride Current Is Dually Regulated by Calcium and Cell Volume
Authors: Chien Li-Ting , Hartzell H. Criss
Published: October 2007

Mutations in the human bestrophin-1 (hBest1) gene are responsible for Best vitelliform macular dystrophy, however the mechanisms leading to retinal degeneration have not yet been determined because the function of the bestrophin protein is not fully understood. Bestrophins have been proposed to comprise a new family of Cl− channels that are activated by Ca2+. While the regulation of bestrophin currents has focused on intracellular Ca2+, little is known about other pathways/mechanisms that may also regulate bestrophin currents. Here we show that Cl− currents in Drosophila S2 cells, that we have previously shown are mediated by bestrophins, are dually regulated by Ca2+ and cell volume. The bestrophin Cl− currents were activated in a dose-dependent manner by osmotic pressure differences between the internal and external solutions. The increase in the current was accompanied by cell swelling. The volume-regulated Cl− current was abolished by treating cells with each of four different RNAi constructs that reduced dBest1 expression. The volume-regulated current was rescued by transfecting with dBest1. Furthermore, cells not expressing dBest1 were severely depressed in their ability to regulate their cell volume. Volume regulation and Ca2+ regulation can occur independently of one another: the volume-regulated current was activated in the complete absence of Ca2+ and the Ca2+-activated current was activated independently of alterations in cell volume. These two pathways of bestrophin channel activation can interact; intracellular Ca2+ potentiates the magnitude of the current activated by changes in cell volume. We conclude that in addition to being regulated by intracellular Ca2+, Drosophila bestrophins are also novel members of the volume-regulated anion channel (VRAC) family that are necessary for cell volume homeostasis.
AMP N1‐Oxide, a Unique Compound of Royal Jelly, Induces Neurite Outgrowth from PC12 Vells via Signaling by Protein Kinase A Independent of that by Mitogen‐Activated Protein Kinase
Authors: Hattori Noriko , Nomoto Hiroshi , Fukumitsu Hidefumi , Mishima Satoshi , Furukawa Shoei
Published: October 2007

Earlier we identified adenosine monophosphate (AMP) N1‐oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth (neuritegenesis) from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N1‐oxide stimulated the phosphorylation of not only mitogen‐activated protein kinase (MAPK) but also that of cAMP/calcium‐response element‐binding protein (CREB) in a dose‐dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N1‐oxide‐induced neuritegenesis, whereas that of protein kinase A (PKA) by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N1‐oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth‐promoting activity. KT5720 restored the growth of AMP N1‐oxide‐treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N1‐oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor‐mediated PKA signaling, which may be responsible for characteristic actions of RJ.