bluuebunny/crossref_metadata_2025 huggingface dataset:
Pointing stabilization of a high-repetition-rate high-power femtosecond laser for intense few-cycle pulse generation
Authors: Kanai Takuya , Suda Akira , Bohman Samuel , Kaku Masanori , Yamaguchi Shigeru , Midorikawa Katsumi
Published: February 2008

We have developed a beam stabilization system for high-power femtosecond lasers operating at a repetition rate of 1kHz. The beam pointing at a hollow fiber input was stabilized to within 1μm rms and the fluctuations of the broadened spectra and power were significantly improved. This technique enables us to increase the input power to a hollow fiber for intense few-cycle pulse generation.
Thin BaHfO3 high-k dielectric layers on TiN for memory capacitor applications
Authors: Lupina G. , Kozłowski G. , Dabrowski J. , Wenger Ch. , Dudek P. , Zaumseil P. , Lippert G. , Walczyk Ch. , Müssig H.-J.
Published: February 2008

Thin BaHfO3 dielectric films were investigated in view of future dynamic random access memory applications. The dielectric layers were prepared by physical vapor codeposition of BaO and HfO2 onto metallic TiN substrates. Films deposited at 400°C are amorphous, show low leakage [J(1V)<10−8A∕cm2] at capacitance equivalent thicknesses (CETs) down to ∼2nm and a dielectric constant of ∼23. Rapid thermal annealing of the amorphous BaHfO3 films induces crystallization in the cubic perovskite phase with a dielectric constant of ∼38. This k value was observed for films as thin as 8nm enabling CET value of ∼0.9nm.
GaN doped with neodymium by plasma-assisted molecular beam epitaxy
Authors: Readinger E. D. , Metcalfe G. D. , Shen H. , Wraback M.
Published: February 2008

We report in situ doping of GaN with the rare earth element Nd by plasma-assisted molecular beam epitaxy. For the highest Nd effusion cell temperatures, Rutherford backscattering and secondary ion mass spectroscopy data indicate ∼5at.% Nd in epilayers grown on c-plane sapphire. X-ray diffraction found no evidence of phase segregation under nitrogen-rich conditions with up to ∼1at.% Nd, with the highest luminescence intensities corresponding to doping of ∼0.5at.%. Spectral correlation of the Nd emission multiplets for above (325nm) and below (836nm) GaN bandgap excitations implies enhanced substitutional doping at the Ga site.
Gas field ion source from an Ir∕W⟨111⟩ single-atom tip
Authors: Kuo Hong-Shi , Hwang Ing-Shouh , Fu Tsu-Yi , Lu Yi-Hsien , Lin Chun-Yueh , Tsong Tien T.
Published: February 2008

We show that a thermally stable Ir∕W⟨111⟩ single-atom tip is a very good point ion source for rare gases (He, Ar) and reactive gases (H2, O2). The ion beams are emitted from the topmost atom with a very small opening angle (<1°) and, most importantly, they exhibit high brightness. In addition, the ion currents are very stable. These good properties together with the long lifetime of the tip and the reliable tip preparation method make this tip especially suitable for applications in gas field ion source focused ion beam systems.
The effect of Ti doping on the growth of Mg nanostructures by oblique angle codeposition
Authors: He Yuping , Zhao Yiping , Wu Jinsong
Published: February 2008

Using an oblique angle codeposition technique, 0–8at.% Ti has been doped into Mg and aligned nanostructure arrays, composed of hexagonal Mg single crystals with preferred orientations, are formed. Ti doping produces nanorod structures instead of the nanoblade structures that are formed from pure Mg deposition. This is due to the pinning effect of Ti for Mg adatom diffusion. There is a linear shift of the Mg diffraction peaks toward the higher 2θ angles with the Ti dopant concentration. This is possibly caused by the partial substitution of large Mg atoms by small Ti atoms.
Conversion of mechanical work to interfacial tension in a nanoporous silica gel
Authors: Qiao Yu , Punyamurtula Venkata K. , Xian Guijun , Karbhari Vistasp M. , Han Aijie
Published: February 2008

A calometric measurement is performed to analyze energy exchange in a nanoporous material functionalized (NMF) liquid. As an external pressure is applied, the hydrophobic nanopore surfaces can be exposed to the liquid phase. When the pressure is removed, the system does not return to its initial configuration. Unlike ordinary energy absorption systems, no significant temperature variation can be detected during the infiltration of pressurized liquid water, indicating that the sorption process is nonexothermic. This is attributed to the conversion of mechanical work to excess solid-liquid interfacial tension.
Plasma power measurement and hysteresis in the E–H transition of a rf inductively coupled plasma system
Authors: Daltrini A. M. , Moshkalev S. A. , Morgan T. J. , Piejak R. B. , Graham W. G.
Published: February 2008

An experimental investigation of the argon plasma behavior near the E–H transition in an inductively coupled Gaseous Electronics Conference reference cell is reported. Electron density and temperature, ion density, argon metastable density, and optical emission measurements have been made as function of input power and gas pressure. When plotted versus plasma power, applied power corrected for coil and hardware losses, no hysteresis is observed in the measured plasma parameter dependence at the E–H mode transition. This suggests that hysteresis in the E–H mode transition is due to ignoring inherent power loss, primarily in the matching system.
Surface passivation and heterojunction cells on Si (100) and (111) wafers using dc and rf plasma deposited Si:H thin films
Authors: Das U. K. , Burrows M. Z. , Lu M. , Bowden S. , Birkmire R. W.
Published: February 2008

The structure of hydrogenated silicon (Si:H) films deposited by rf and dc plasma process on Si (100) and (111) wafers is correlated with the surface passivation quality and heterojunction cell performance. Microstructural defects associated with SiH2 bonding and apparent ion bombardment in dc plasmas have little or no adverse effect on passivation or cell properties, while presence of crystallinity in Si:H i layer severely deteriorates surface passivation and cell open circuit voltage (Voc). Excellent surface passivation (lifetime of >1ms) and high efficiency cells (>18%) with Voc of 694mV are demonstrated on n-type textured Czochralski wafer using dc plasma process.
Spin separation via a three-terminal Aharonov–Bohm interferometers
Authors: Chi Feng , Zheng Jun
Published: February 2008

We propose a three-terminal ring-type device which contains a single-level quantum dot (QD) to extract or separate the spin-up and the spin-down electrons that are injected into the QD from a middle lead, into the left and the right leads, respectively. This scheme is based on the Rashba spin-orbit interaction (RSOI) in the bridge between the left and the right leads and is free from magnetic field or magnetic material. We find that both the spin directions and the magnitude of the outflow currents in the left and the right leads can be tuned by the RSOI strength and the structure parameters.
Nanomechanical properties of few-layer graphene membranes
Authors: Poot M. , van der Zant H. S. J.
Published: February 2008

We have measured the mechanical properties of few-layer graphene and graphite flakes that are suspended over circular holes. The spatial profile of the flake’s spring constant is measured with an atomic force microscope. The bending rigidity of and the tension in the membranes are extracted by fitting a continuum model to the data. For flakes down to eight graphene layers, both parameters show a strong thickness dependence. We predict fundamental resonance frequencies of these nanodrums in the gigahertz range based on the measured bending rigidity and tension.
Metastable behavior of donors in CuGaSe2 under illumination
Authors: Siebentritt Susanne , Rissom Thorsten
Published: February 2008

Several metastable effects have been observed in chalcopyrite solar cells. Recently, they have been related to the amphoteric behavior of the Se vacancy. We give an independent experimental evidence on this amphoteric behavior. By comparing charge carrier densities obtained from Hall effect measurements under illumination and in the dark, we conclude that illumination removes compensating donors.
Photoscattering effect in supercontinuum-generating photonic crystal fiber
Authors: Tu H. , Marks D. L. , Jiang Z. , Boppart S. A.
Published: February 2008

A photosensitivity different from that responsible for fiber grating inscription is found in a supercontinuum-generating photonic crystal fiber transmitting intense 818nm femtosecond pulses. This photosensitivity progressively generates a waveguide at the entrance of the fiber to scatter light of specific wavelengths and is termed as the photoscattering effect. This effect is linked to the ∼800nm photosensitivity in the microlithography of bulk silica glass. While the effect somewhat limits fiber-optic supercontinuum applications, it can be beneficial to produce new photonic devices.
Quantifying changes in the thiol redox proteome upon oxidative stress
in vivo
Authors: Leichert Lars I. , Gehrke Florian , Gudiseva Harini V. , Blackwell Tom , Ilbert Marianne , Walker Angela K. , Strahler John R. , Andrews Philip C. , Jakob Ursula
Published: February 2008

Antimicrobial levels of reactive oxygen species (ROS) are produced by the mammalian host defense to kill invading bacteria and limit bacterial colonization. One main
in vivo
target of ROS is the thiol group of proteins. We have developed a quantitative thiol trapping technique termed OxICAT to identify physiologically important target proteins of hydrogen peroxide (H
2
O
2
) and hypochlorite (NaOCl) stress
in vivo
. OxICAT allows the precise quantification of oxidative thiol modifications in hundreds of different proteins in a single experiment. It also identifies the affected proteins and defines their redox-sensitive cysteine(s). Using this technique, we identified a group of
Escherichia coli
proteins with significantly (30–90%) oxidatively modified thiol groups, which appear to be specifically sensitive to either H
2
O
2
or NaOCl stress. These results indicate that individual oxidants target distinct proteins
in vivo
. Conditionally essential
E. coli
genes encode one-third of redox-sensitive proteins, a finding that might explain the bacteriostatic effect of oxidative stress treatment. We identified a select group of redox-regulated proteins, which protect
E. coli
against oxidative stress conditions. These experiments illustrate that OxICAT, which can be used in a variety of different cell types and organisms, is a powerful tool to identify, quantify, and monitor oxidative thiol modifications
in vivo
.
Anti-Ca
2+
channel antibody attenuates Ca
2+
currents and mimics cerebellar ataxia
in vivo
Authors: Liao Yaping Joyce , Safa Parsa , Chen Yi-Ren , Sobel Raymond A. , Boyden Edward S. , Tsien Richard W.
Published: February 2008

Voltage-gated Ca
2+
channels (VGCCs) are membrane proteins that determine the activity and survival of neurons, and mutations in the P/Q-type VGCCs are known to cause cerebellar ataxia. VGCC dysfunction may also underlie acquired peripheral and central nervous system diseases associated with small-cell lung cancer, including Lambert–Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar ataxia (PCA). The pathogenic role of anti-VGCC antibody in LEMS is well established. Although anti-VGCC antibody is also found in a significant fraction of PCA patients, its contribution to PCA is unclear. Using a polyclonal peptide antibody against a major immunogenic region in P/Q-type VGCCs (the extracellular Domain-III S5–S6 loop), we demonstrated that such antibody was sufficient to inhibit VGCC function in neuronal and recombinant VGCCs, alter cerebellar synaptic transmission, and confer the phenotype of cerebellar ataxia. Our data support the hypothesis that anti-VGCC antibody may play a significant role in the pathogenesis of cerebellar dysfunction in PCA.
Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers
Authors: Gu Frank , Zhang Liangfang , Teply Benjamin A. , Mann Nina , Wang Andrew , Radovic-Moreno Aleksandar F. , Langer Robert , Farokhzad Omid C.
Published: February 2008

There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers
in vivo
. Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, “stealth” properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA-
b
-PEG-
b
-Apt triblock copolymer with PLGA-
b
-PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake
in vitro
and
in vivo
. This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities.
Starvation after AgRP neuron ablation is independent of melanocortin signaling
Authors: Wu Qi , Howell Maureen P. , Cowley Michael A. , Palmiter Richard D.
Published: February 2008

Ablation of inhibitory agouti-related protein (AgRP)-expressing neurons in the arcuate nucleus that also synthesize γ-amino-butyric acid (GABA) and neuropeptide Y in adult mice leads to starvation within 1 week. The removal of inhibition from the AgRP neurons onto neighboring proopiomelanocortin neurons and their common postsynaptic neurons is predicted to stimulate melanocortin signaling, which is known to inhibit appetite. To examine the importance of uncontrolled melanocortin signaling in mediating starvation in this model, we ablated AgRP neurons in

A
y
/a

mice that have chronic blockade of the melanocortin signaling. The blockade of melanocortin signaling did not ameliorate the rate of starvation. On both WT and

A
y
/a

genetic backgrounds, there was a progressive decrease in meal frequency after AgRP neuron ablation. Surprisingly, intraoral feeding also was dramatically reduced after the ablation of AgRP neurons. These results indicate that both the appetitive and consummatory aspects of feeding become impaired in a melanocortin-independent manner after AgRP neuron ablation.
Multifocal Ductal Cell Hyperplasia in the Submandibular Salivary Glands of Wistar Rats Chronically Treated with a Novel Steroidal Compound
Authors: De Rijk Eveline P.C.T. , Ravesloot Wilma T.M. , Hafmans Theo G.M. , Van Esch Eric
Published: February 2008

A high incidence of multifocal ductal hyperplasia was observed in the submandibular salivary gland of rats treated for 26 weeks with a high dose of a novel synthetic steroid with combined estrogenic and progestagenic properties. Hyperplastic foci consisted of microcystic duct-like structures lined by a single or multilayered epithelium, sometimes showing a tendency towards a cribiform growth pattern. The hyperplastic ducts were embedded in a collagen-rich stroma and surrounded by numerous myoepithelial cells. Immunohistochemical methods used for the detection of estrogen- and progesterone receptors revealed that progesterone receptors were abundantly present in the nucleus of epithelial cells within the lesions, exclusively. Estrogen receptors could not be detected in both the normal tissue and hyperplasic foci. The morphological, ultrastructural, and immunohistochemical characteristics strongly suggest that these hyperplastic lesions originated from the intercalated ducts. The rodent-specific granular duct cell was not involved in the pathogenesis as was clearly demonstrated by the lack of immunoreactive epidermal growth factor within the lesions. Lesions were not observed in studies with progestagens and estrogens alone or with other combined estrogen/progestagen compounds, suggesting that the specific ratio of estrogenic and progestagenic activity of the present steroid had played an important role in the development of ductal hyperplasia in this study. Lesions of the intercalated ducts, as described in this study, have not been reported before in the literature.
Overexpression of Aryl Hydrocarbon Receptor in Human Lung Carcinomas
Authors: Pinpin Lin  , Han Chang  , Tsai Wen-Tin , Wu Meng-Hsiang , Liao Yung-Shen , Chen Jung-Ta , Su Jang-Ming
Published: February 2008

Exposure to polycylic aromatic hydrocarbons (PAH) has been associated with increased risk of lung cancer. Aryl hydrocarbon receptor (AhR) is known to play an essential role in PAH-induced toxicity. The objectives of this study were to identify and evaluate AhR expression in normal human lung tissues and in lung carcinomas. AhR protein and mRNA levels in human lung cell lines were evaluated with immunoblot and quantitative real-time RT-PCR assays, respectively. AhR protein expression was high in cytosol homogenates of adenocarcinoma (AD) cell lines and AhR mRNA levels corresponded well with AhR protein levels in these cell lines. AhR expression in human lung tissues and carcinomas were examined by means of immunohistochemical staining method. In normal lung tissues, immunostaining was found in the cytosol of bronchiolar epithelial cells. AhR immunostaining was more intense in AD than in squamous cell carcinomas. When AhR expression was compared with normal bronchiolar epithelial cells and neoplastic cells in the same specimens, the neoplastic cells, especially those of AD, demonstrated an increased staining. The upregulation of AhR mRNA expression was also demonstrated among 2 of 4 paired tissues with the quantitative real-time RT-PCR assay. Our data indicated that AhR expression was upregulated in lung AD and suggested that AhR and its expression might play an important role in the development of lung AD.
Value of GST-P Positive Preneoplastic Hepatic Foci in Dose-Response Studies of Hepatocarcinogenesis: Evidence for Practical Thresholds with Both Genotoxic and Nongenotoxic Carcinogens. A Review of Recent Work
Authors: Tsuda Hiroyuki , Fukushima Shoji , Wanibuchi Hideki , Morimura Kechirou , Nakae Dai , Imaida Katsumi , Tatematsu Masae , Hirose Masao , Wakabayashi Keiji , Moore Malcolm A.
Published: February 2008

Recent low-dose carcinogenesis studies, including major group projects are reviewed. The prevailing paradigm is that carcinogens, particularly genotoxic compounds, have no threshold in exerting their potential for cancer induction. However, the nonthreshold hypothesis can be challenged for cancer risk assessment in humans. A recent very large-scale cooperative effort in Japan furthermore showed that the genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5- f ]quinoxaline, forms DNA adducts and 8-hydroxy-2'-deoxyguanosine at low doses, but does not induce glutathione S-transferase placental form (GST-P) positive foci as preneoplastic lesions in rat liver (≤10 ppm in diet). Moreover, very low doses of a N-nitroso compound, diethylnitrosamine (DEN), were also found not to significantly induce GST-P positive foci in rat liver (≤0.01 ppm in drinking water). Given the direct correlation between induction of the preneoplastic lesions in the short-term and carcinomas in the longer term with different carcinogens, the results imply a practical nonobserved effect level for hepatocarcinogenicity. Similar results were also observed with so-called nongenotoxic carcinogens such as phenobarbital (PB) and p, p'-dichlorodiphenyltrichloroethane (DDT), which do not exert positive effects on lesion development at very low doses. Furthermore, experiments with application of PB and DDT after treatment with DEN indicate that at very low doses (≤2 ppm in diet), they may even inhibit the development of GST-P positive foci. The data reviewed provide evidence that preneoplastic foci in the liver can be employed as end-point lesions in place of tumors and that exposure to very low levels of carcinogens, typical of those found in the human environment, does not necessarily present as a risk factor.
Validation and Regulatory Acceptance of New Carcinogenicity Tests
Authors: Spielmann Horst
Published: February 2008

The 3 Rs concept, which was developed by Russell and Burch in 1959, was implemented into the legal framework in the European Union (EU) for the protection of vertebrate animals used for experimental and other scientific purposes, when Directive 86/609/EEC was adopted in 1986. To reduce or replace animal testing for regulatory purposes, nonanimal tests must be independently validated to prove that they can provide information that is relevant and reliable for hazard prediction in vivo. At the end of the 1980s, no scientific concept existed for the formal validation of in vitro toxicity tests, so a small group of European and American scientists developed a set of principles for experimental validation, which was accepted internationally by the OECD in 1996. A major breakthrough was the acceptance in the EU of the scientifically validated in vitro toxicity test for phototoxic potential in 2000, which was accepted by the OECD at the worldwide level in 2002. Taking the progress in the development and validation of alternative toxicity tests during the past decade into account, the current concepts of developing alternatives to the standard 2-year rodent bioassay for carcinogenicity testing are discussed.
Relevance of Hepatic Preneoplasia for Human Hepatocarcinogenesis
Authors: Qin Su  , Bannasch Peter
Published: February 2008

Different lesions have been suggested to represent preneoplastic conditions in human liver. They include liver cell dysplasia, separated in large-cell change (LCC) and small-cell change (SCC), adenomatoid hyperplasia, and the more recently identified foci of altered hepatocytes (FAH) and nodules of altered hepatocytes (NAH). FAH have been demonstrated to represent preneoplastic lesions in various animal models of hepatocarcinogenesis. To demonstrate prevalence and significance of FAH in the human liver, the cellular composition, size distribution, and proliferation kinetics of these lesions were studied in 163 explanted and resected human livers with or without hepatocellular carcinoma (HCC). FAH including glycogen-storing foci (GSF), mixed cell foci (MCF), and basophilic cell foci were found in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with than without HCC. MCF, predominant in cirrhotic livers of the high-risk group, were more proliferative, larger and more often involved in formation of NAH than GSF. The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSF. We also investigated the relationship of FAH to liver cell dysplasia. Occurrence of SCC, rather than that of LCC, confers FAH an increased proliferation activity and higher risk to nodular transformation, and, hence, should be considered a precancerous condition. Histological detection of FAH and SCC through needle-aspiration liver biopsy can be used for monitoring HCC development in high-risk populations, such as HBV carriers with chronic hepatitis and/or cirrhosis.
Induction and Modulation of Hepatic Preneoplasia and Neoplasia in the Rat by Dehydroepiandrosterone
Authors: Mayer Doris , Forstner Klaus , Kopplow Kathrin
Published: February 2008

Dehydroepiandrosterone (DHEA), the main adrenal steroid in humans and a precursor in androgen and estrogen biosynthesis, acts as a peroxisome proliferator and as a hepatocarcinogen in rats. Neoplasms emerge from a glycogenotic/amphophilic/basophilic preneoplastic cell lineage. A higher female tumor incidence suggests a relevant influence of sex hormones. DHEA enhances hepatocarcinogenesis induced by N-nitrosomorpholine (NNM), which is characterized by the glycogenotic/basophilic cell lineage. The tumor promoting effect is related to an additional amphophilic/basophilic preneoplastic lesion sequence and to faster proliferation of the basophilic preneoplastic lesions. Nevertheless, hepatocellular carcinomas provided under DHEA treatment seem to have a less malignant phenotype compared to tumors induced by NNM only. Further, DHEA treatment reduces growth and generation of glycogen storage foci (GSF) in initial NNM-treated rats. Thus, DHEA treatment results in both, a growth stimulation of the late basophilic lesion type with an additional amphophilic lesion sequence, and in a growth inhibition of early preneoplastic lesions, addressing especially GSF. DHEA also inhibits the growth of physiologically proliferating liver tissue. This might be explained by a DHEA related cellular metabolism, which results in significant energy consumption. Additionally, a DHEA-induced alteration of cytokine levels might contribute to this growth inhibition as well.
Mechanisms of Promotion and Progression of Preneoplastic Lesions in Hepatocarcinogenesis by DDT in F344 Rats
Authors: Harada Takanori , Yamaguchi Satoru , Ohtsuka Ryoichi , Takeda Makio , Fujisawa Hideki , Yoshida Toshinori , Enomoto Akiko , Chiba Yuko , Fukumori Junko , Kojima Sayuri , Tomiyama Naruto , Saka Machiko , Ozaki Masakazu , Maita Keizo
Published: February 2008

Time-related changes in potential factors involved in hepatocarcinogenesis by DDT were investigated in a 4-week and a 2-year feeding studies of p, p'-DDT with F344 rats. In the 4-week study with males at doses of 50, 160, and 500 ppm, cell proliferation and gap junctional intercellular communication (GJIC) were examined after 1, 2, 3, 7, 14, and 28 days. Cell proliferation was enhanced within 3 days at any dose level, but returned to normal after 7 days, whereas GJIC was inhibited throughout the study. In the 2-year study with both sexes at doses of 5, 50, and 500 ppm, cell proliferation, GJIC, enzyme induction, and oxidative stress were investigated after 26, 52, 78, and 104 weeks. Males and females showed an inhibition of GJIC and increases in P450 isozymes (CYP2B1 and CYP3A2) in a dose-dependent manner at all time points, but no significant change in cell proliferation. Lipid peroxide for males at 50 and 500 ppm and 8-hydroxydeoxyguanosine for both sexes at 500 ppm were elevated throughout the study. Histologically, eosinophilic foci and hepatocellular adenomas increased in males at 50 ppm and both sexes at 500 ppm. Hepatocellular carcinomas also developed in males at 500 ppm. These results indicate that DDT may induce eosinophilic foci as a result of oxidative DNA damage and leads them to neoplasms in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.
Neutral beam injection heating on field-reversed configuration plasma decompressed through axial translation
Authors: Inomoto Michiaki , Asai Tomohiko , Okada Shigefumi
Published: February 2008

The power deposition of neutral beam injection (NBI) on translated field-reversed configuration (FRC) plasma has been investigated. A certain level of electron heating effect was observed in the slowly decaying phase of the decompressed FRC, leading to a hollow electron temperature profile. Numerical calculation of beam trajectories has shown that about 50% of the injected NB power is absorbed by the plasma electron inside the separatrix with a hollow deposition profile similar to the observed electron temperature profile. The estimated absorbed NB power of 120 kW will be enough to bring the change in electron temperature, since the electron conduction and radiation loss was estimated to be ∼100 kW.
Current drive and heating by fusion protons in a D–3He FRC reactor
Authors: Ferrari Hugo E. , Farengo Ricardo
Published: February 2008

The possibility of using the 14.7 MeV protons produced in the D-3He fusion reaction to sustain the current and heat the plasma in a field reversed configuration reactor is investigated. A Monte Carlo code that includes particle drag and pitch angle scattering is employed to follow the trajectories of the fusion born protons and calculate the resulting current and deposited power. It is found that for the parameters of the proposed ARTEMIS (Momotaet al1992Fusion Technol.212307) conceptual reactor design a significant current (40–46 MA) could result, depending on the plasma current induced by the protons, which is not calculated. The effect of changing the shape of the plasma equilibrium is also investigated.
Experiment on direct energy conversion from tandem mirror plasmas by using a slanted cusp magnetic field
Authors: Yasaka Y. , Yamamoto T. , Kurumatani Y. , Takeno H. , Nakashima Y. , Cho T. , Tomita Y. , Ishikawa M.
Published: February 2008

A direct energy converter (DEC) designed for thermal ions escaping from a linear or near-linear device consists of a cusp magnetic field and decelerating electrodes. The electrons are deflected along the field lines and consequently separated from ions that are not fully magnetized. The ions are led to the decelerating electrodes to produce dc power. This type of DEC, the CUSPDEC, is applied to the GAMMA 10 tandem mirror in order to investigate the capability of separation of charged particles as well as to demonstrate energy conversion from ions. The separation of electrons and ions with energies of the order of kilo-electron Volt is achieved by using a slanted cusp magnetic field for the first time. It is also demonstrated that the separated ions are decelerated by the electric field in front of ion collectors and flow into the collectors at a high potential to produce electricity.
Mammalian Septins Are Required for Phagosome Formation
Authors: Huang Yi-Wei , Yan Ming , Collins Richard F. , DiCiccio Jessica E. , Grinstein Sergio , Trimble William S.
Published: February 2008

Septins are members of a highly conserved family of filamentous proteins that are required in many organisms for the completion of cytokinesis. In addition, septins have been implicated in a number of important cellular processes and have been suggested to have roles in regulating membrane traffic. Given the proposed role of septins in cell membrane dynamics, we investigated the function of septins during FcγR-mediated phagocytosis. We show that several septins are expressed in RAW264.7 and J774 mouse macrophage cell lines and that SEPT2 and SEPT11 are colocalized with submembranous actin-rich structures during the early stages of FcγR-mediated phagocytosis. In addition, SEPT2 accumulation is seen in primary human neutrophils and in nonprofessional phagocytes. The time course of septin accumulation mirrors actin accumulation and is inhibited by latrunculin and genistein, but not other inhibitors of phagocytosis. Inhibition of septin function by transient expression of the BD3 domain of BORG3, known to cause septin aggregation, or depletion of SEPT2 or SEPT11 by RNAi, significantly inhibited FcγR-mediated phagocytosis of IgG-coated latex beads. Interestingly, this occurred without affecting the accumulation of actin or the actin-associated protein coronin-1. These observations show that, although not necessary for actin recruitment, septins are required for efficient FcγR-mediated phagocytosis.
RASSF7 Is a Member of a New Family of RAS Association Domain–containing Proteins and Is Required for Completing Mitosis
Authors: Sherwood Victoria , Manbodh Ria , Sheppard Carol , Chalmers Andrew D.
Published: February 2008

Mitosis is a fundamental feature of all cellular organisms. It must be tightly regulated to allow normal tissue growth and to prevent cancer formation. Here, we identify a new protein that is required for mitosis. We show that the Ras association (RA) domain–containing protein, RASSF7, is part of an evolutionarily conserved group of four proteins. These are RASSF7, RASSF8, and two new RASSF proteins P-CIP1/RASSF9 and RASSF10. We call this group the N-terminal RASSF family. We analyzed the function of Xenopus RASSF7. RASSF7 was found to be expressed in several embryonic tissues including the skin, eyes, and neural tube. Knocking down its function led to cells failing to form a mitotic spindle and arresting in mitosis. This caused nuclear breakdown, apoptosis, and a striking loss of tissue architecture in the neural tube. Consistent with a role in spindle formation, RASSF7 protein was found to localize to the centrosome. This localization occurred in a microtubule-dependent manner, demonstrating that there is a mutually dependant relationship between RASSF7 localization and spindle formation. Thus RASSF7, the first member of the N-terminal RASSF family to be functionally analyzed, is a centrosome-associated protein required to form a spindle and complete mitosis in the neural tube.
Formation of E-Cadherin/β-Catenin–based Adherens Junctions in Hepatocytes Requires Serine-10 in p27(Kip1)
Authors: Théard Delphine , Raspe Marcel A. , Kalicharan Dharamdajal , Hoekstra Dick , van IJzendoorn Sven C.D.
Published: February 2008

The adhesion between epithelial cells at adherens junctions is regulated by signaling pathways that mediate the intracellular trafficking and assembly of its core components. Insight into the molecular mechanisms of this is necessary to understand how adherens junctions contribute to the functional organization of epithelial tissues. Here, we demonstrate that in human hepatic HepG2 cells, oncostatin M-p42/44 mitogen-activated protein kinase signaling stimulates the phosphorylation of p27(Kip1) on Ser-10 and promotes cell–cell adhesion. The overexpression of wild-type p27 or a phospho-mimetic p27S10D mutant in HepG2 cells induces a hyper-adhesive phenotype. In contrast, the overexpression of a nonphosphorylatable p27S10A mutant prevents the mobilization of E-cadherin and β-catenin at the cell surface, reduces basal cell–cell adhesion strength, and prevents the stimulatory effect of oncostatin M on cell–cell adhesion. As part of the underlying molecular mechanism, it is shown that in p27S10A-expressing cells β-catenin interacts with p27 and is prevented from interacting with E-cadherin. The intracellular retention of E-cadherin and β-catenin is also observed in hepatocytes from p27S10A knockin mice that express the p27S10A mutant instead of wild-type p27. Together, these data suggest that the formation of adherens junctions in hepatocytes requires Ser-10 in p27.
Nebulin Interacts with CapZ and Regulates Thin Filament Architecture within the Z-Disc
Authors: Pappas Christopher T. , Bhattacharya Nandini , Cooper John A. , Gregorio Carol C.
Published: February 2008

The barbed ends of actin filaments in striated muscle are anchored within the Z-disc and capped by CapZ; this protein blocks actin polymerization and depolymerization in vitro. The mature lengths of the thin filaments are likely specified by the giant “molecular ruler” nebulin, which spans the length of the thin filament. Here, we report that CapZ specifically interacts with the C terminus of nebulin (modules 160–164) in blot overlay, solid-phase binding, tryptophan fluorescence, and SPOTs membrane assays. Binding of nebulin modules 160–164 to CapZ does not affect the ability of CapZ to cap actin filaments in vitro, consistent with our observation that neither of the two C-terminal actin binding regions of CapZ is necessary for its interaction with nebulin. Knockdown of nebulin in chick skeletal myotubes using small interfering RNA results in a reduction of assembled CapZ, and, strikingly, a loss of the uniform alignment of the barbed ends of the actin filaments. These data suggest that nebulin restricts the position of thin filament barbed ends to the Z-disc via a direct interaction with CapZ. We propose a novel molecular model of Z-disc architecture in which nebulin interacts with CapZ from a thin filament of an adjacent sarcomere, thus providing a structural link between sarcomeres.
Pxl1p, a Paxillin-related Protein, Stabilizes the Actomyosin Ring during Cytokinesis in Fission Yeast
Authors: Ge Wanzhong , Balasubramanian Mohan K.
Published: February 2008

Paxillins are a family of conserved LIM domain-containing proteins that play important roles in the function and integrity of the actin cytoskeleton. Although paxillins have been extensively characterized by cell biological and biochemical approaches, genetic studies are relatively scarce. Here, we identify and characterize a paxillin-related protein Pxl1p in the fission yeast Schizosaccharomyces pombe. Pxl1p is a component of the fission yeast actomyosin ring, a structure that is essential for cytokinesis. Cells deleted for pxl1 display a novel phenotype characterized by a splitting of the actomyosin ring in late anaphase, leading to the formation of two rings of which only one undergoes constriction. In addition, the rate of actomyosin ring constriction is slower in the absence of Pxl1p. pxl1Δ mutants display strong genetic interactions with mutants defective in IQGAP-related protein Rng2p and mutants defective in components of the fission yeast type II myosin machinery. Collectively, these results suggest that Pxl1p might cooperate with type II myosin and Rng2p-IQGAP to regulate actomyosin ring constriction as well as to maintain its integrity during constriction.
Cis-Dimerization Mediates Function of Junctional Adhesion Molecule A
Authors: Severson Eric A. , Jiang Liangyong , Ivanov Andrei I. , Mandell Kenneth J. , Nusrat Asma , Parkos Charles A.
Published: February 2008

Junctional adhesion molecule-A (JAM-A) is a transmembrane component of tight junctions that has been proposed to play a role in regulating epithelial cell adhesion and migration, yet mechanistic structure–function studies are lacking. Although biochemical and structural studies indicate that JAM-A forms cis-homodimers, the functional significance of dimerization is unclear. Here, we report the effects of cis-dimerization–defective JAM-A mutants on epithelial cell migration and adhesion. Overexpression of dimerization-defective JAM-A mutants in 293T cells inhibited cell spreading and migration across permeable filters. Similar inhibition was observed with using dimerization-blocking antibodies. Analyses of cells expressing the JAM-A dimerization-defective mutant proteins revealed diminished β1 integrin protein but not mRNA levels. Further analyses of β1 protein localization and expression after disruption of JAM-A dimerization suggested that internalization of β1 integrin precedes degradation. A functional link between JAM-A and β1 integrin was confirmed by restoration of cell migration to control levels after overexpression of β1 integrin in JAM-A dimerization-defective cells. Last, we show that the functional effects of JAM dimerization require its carboxy-terminal postsynaptic density 95/disc-large/zonula occludins-1 binding motif. These results suggest that dimerization of JAM-A regulates cell migration and adhesion through indirect mechanisms involving posttranscriptional control of β1 integrin levels.
Na/H Exchange Regulatory Factor 1, a Novel AKT-associating Protein, Regulates Extracellular Signal-regulated Kinase Signaling through a B-Raf–Mediated Pathway
Authors: Wang Bin , Yang Yanmei , Friedman Peter A.
Published: February 2008

Na/H exchange regulatory factor 1 (NHERF1) is a scaffolding protein that regulates signaling and trafficking of several G protein-coupled receptors (GPCRs), including the parathyroid hormone receptor (PTH1R). GPCRs activate extracellular signal-regulated kinase (ERK)1/2 through different mechanisms. Here, we characterized NHERF1 regulation of PTH1R-stimulated ERK1/2. Parathyroid hormone (PTH) stimulated ERK1/2 phosphorylation by a protein kinase A (PKA)-dependent, but protein kinase C-, cyclic adenosine 5′-monophosphate-, and Rap1-independent pathway in Chinese hamster ovary cells stably transfected with the PTH1R and engineered to express NHERF1 under the control of tetracycline. NHERF1 blocked PTH-induced ERK1/2 phosphorylation downstream of PKA. This suggested that NHERF1 inhibitory effects on ERK1/2 occur at a postreceptor locus. Forskolin activated ERK1/2, and this effect was blocked by NHERF1. NHERF1 interacted with AKT and inhibited ERK1/2 activation by decreasing the stimulatory effect of 14-3-3 binding to B-Raf, while increasing the inhibitory influence of AKT negative regulation on ERK1/2 activation. This novel regulatory mechanism provides a new model by which cytoplasmic adapter proteins modulate ERK1/2 activation through a receptor-independent mechanism involving B-Raf.
Exploring a first-principles-based model for zooplankton respiration
Authors: Packard Ted T. , Gómez May
Published: February 2008

Packard, T. T., and Gómez, M. 2008. Exploring a first-principles-based model for zooplankton respiration. – ICES Journal of Marine Science, 65: 371–378. Oxygen consumption (R) is caused by the respiratory electron transfer system (ETS), not biomass. ETS is ubiquitous in zooplankton, determines the level of potential respiration (Φ), and is the enzyme system that ultimately oxidizes the products of food digestion, makes ATP, and consumes O2. Current respiration hypotheses are based on allometric relationships between R and biomass. The most accepted version at constant temperature (T) is R = i0M0.75, where i0 is a constant. We argue that, for zooplankton, a Φ-based, O2-consuming algorithm is more consistent with the cause of respiration. Our point: although biomass is related to respiration, the first-principles cause of respiration is ETS, because it controls O2 consumption. Biomass itself is indirectly related to respiration, because it packages the ETS. Consequently, we propose bypassing the packaging and modelling respiration from ETS and hence Φ. This Φ is regulated by T, according to Arrhenius theory, and by specific reactants (S) that sustain the redox reactions of O2 consumption, according to Michaelis–Menten kinetics. Our model not only describes respiration over a large range of body sizes but also explains and accurately predicts respiration on short time-scales. At constant temperature, our model takes the form: where Ea is the Arrhenius activation energy, Rg, the gas constant, and Km, the Michaelis–Menten constant.
High NT‐proBNP Is a Strong Predictor of Outcome in Elderly Heart Failure Patients
Authors: Andersson Sven E. , Edvinsson Marie‐Louise , Björk Jonas , Edvinsson Lars
Published: February 2008

All patients older than 65 years (184 men; mean age, 78±0.8 years/181 women; mean age, 82±0.6 years) seeking medical attention at the Lund University Hospital Emergency Clinic during a 2‐year period who had an N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) value >2000 pg/mL were followed up for survival. Mortality in the entire population was 21% after 3 months, 35% after 1 year, and 40% after 2 years. Multivariate analysis indicated that the NT‐proBNP level and the New York Heart Association (NYHA) functional class were stronger predictors of mortality than were echocardiographic estimation of left ventricular ejection fraction or chest radiography. Patients who survived the first year were younger, had higher systolic blood pressure, had lower plasma creatinine, had lower inflammatory activity, and were treated with lower doses of furosemide. The results indicate that in this population, NT‐proBNP level together with assessment of NYHA class gives the best prognostic information of 1‐year mortality.
The Women's Initiative for Nonsmoking (WINS) XI: Age‐Related Differences in Smoking Cessation Responses Among Women With Cardiovascular Disease
Authors: Doolan Daniel M. , Stotts Nancy A. , Benowitz Neil L. , Covinsky Kenneth E. , Froelicher Erika S.
Published: February 2008

Smoking cessation has immediate health benefits; however, the efficacy of smoking cessation interventions among older adults and women has received limited research attention. The original Women's Initiative for Nonsmoking (WINS) study was a randomized controlled trial that tested the efficacy of a smoking cessation intervention for Bay Area women hospitalized with cardiovascular disease. The current study, which used the WINS dataset, compares participants 62 and older with those younger than 62 years. The sample (n=277) contained 136 older smokers and 141 younger smokers. At the 6‐month follow‐up, 52.1% of older smokers had quit smoking compared with 40.6% of younger smokers. At the 12‐month follow‐up, 52.0% of older smokers had quit smoking compared with 38.1% of younger smokers. The difference at 12 months was statistically significant, and a Kaplan‐Meier survival analysis further supported these findings. Clinicians should be sure to also include older smokers in smoking assessments and smoking cessation interventions.

(Am J Geriatr Cardiol. 2008;17:37–47)
Ethical Issues in the Management of Geriatric Cardiac Patients Hannah I. Lipman, MD, Section Editor From the Department of Medicine, Divisions of Geriatrics and Cardiology, Montefiore Medical Center of the Albert Einstein College of Medicine, Bronx, NY
Authors: Holtey Blair , Basta Lofty
Published: February 2008

Ethical Issue:

Participating physicians failed to properly document that the patient had no reasonable expectation of recovery. This caused a delay in the initiation of discussion concerning end‐of‐life.
Ctf1, a transcriptional activator of cutinase and lipase genes in Fusarium oxysporum is dispensable for virulence
Authors: ROCHA ANA LILIA MARTÍNEZ , DI PIETRO ANTONIO , RUIZ‐ROLDÁN CARMEN , RONCERO M. ISABEL G.
Published: February 2008

Cutinolytic enzymes are secreted by fungal pathogens attacking the aerial parts of the plant, to facilitate penetration of the outermost cuticular barrier of the host. The role of cutinases in soil‐borne root pathogens has not been studied thus far. Here we report the characterization of the zinc finger transcription factor Ctf1 from the vascular wilt fungus Fusarium oxysporum, a functional orthologue of CTF1α that controls expression of cutinase genes and virulence in the pea stem pathogen Fusarium solani f. sp. pisi. Mutants carrying a Δctf1 loss‐of‐function allele grown on inducing substrates failed to activate extracellular cutinolytic activity and expression of the cut1 and lip1 genes, encoding a putative cutinase and lipase, respectively, whereas strains harbouring a ctf1C allele in which the ctf1 coding region was fused to the strong constitutive Aspergillus nidulans gpdA promoter showed increased induction of cutinase activity and gene expression. These results suggest that F. oxysporum Ctf1 mediates expression of genes involved in fatty acid hydrolysis. However, expression of lip1 during root infection was not dependent on Ctf1, and virulence of the ctf1 mutants on tomato plants and fruits was indistinguishable from that of the wild‐type. Thus, in contrast to the stem pathogen F. solani, Ctf1 is not essential for virulence in the root pathogen F. oxysporum.